Volker Bühler

Generic Drug Formulations

Fine Chemicals
(2nd edition 1998)

1 Introduction
1.1 Preface
A selection of about 500 formulations
of human and veterinary drugs are
presented in this booklet. They have
all been developed in the last 20
years in the Applications Laboratories
of BASF AG and are in solid, liquid,
and semi-solid form. However, emphasis is placed on tablets. Human
and veterinary medicines have not
been dealt with in separate chapters,
because the technologies and excipients are the same.

Select the required formulation in
the following list of all formulations by clicking with the cursor.

BASF Fine Chemicals Generic Drug Formulations 1997

1.2 List of all formulations aranged alphabetically
A
Aceclofenac Gel-Cream (1.5 %)
Aceclofenac Instant Granules (1.3 %)
Acetaminophen see Paracetamol
Acetylsalicylic Acid + Paracetamol
+ Caffeine Tablets
(250 mg + 250 mg + 50 mg)
Acetylsalicylic Acid + Paracetamol
+ Caffeine Tablets
(400 mg + 100 mg + 30 mg)
Acetylsalicylic Acid + Paracetamol
Tablets (250 mg + 250 mg)
Acetylsalicylic Acid + Vitamin C Tablets
(325 mg + 250 mg)
Acetylsalicylic Acid Tablets (400 mg)
Acetylsalicylic Acid Tablets (500 mg)
Acyclovir Oral Suspension (2 %)
Albendazole Dry Syrup or Instant
Granules (200 mg)
Albendazole Tablets (100 mg)
Alginic Acid + Aluminium Hydroxide +
Magnesium Silicate Tablets
(500 mg + 100 mg + 25 mg)
Aloe Vera Gel
Alpha-Bisabolol
Aqueous Mouth Wash Solution
(0.2 %)
Alpha-Bisabolol Buccal or Topical
Solution (0.1%)
Alpha-Bisabolol Ethanolic Mouth
Wash Solution (1%)
Alpha-Bisabolol Mouth Wash Solution
(0.5 %)
Alpha-Methyldopa Tablet Cores
(250 mg), DC
Alpha-Methyldopa Tablet Cores
(250 mg), WG
Alpha-Methyldopa Tablets
(500 mg), DC
Alpha-Methyldopa Tablets
(500 mg), WG
Alprazolam Tablets (0.5 mg)

Aluminium Acetylsalicylate Tablets
(250 mg)
Aluminium Hydroxide + Magnesium
Carbonate Dry Syrup
Aluminium hydroxide + Magnesium
carbonate/oxide + Simethicone
Tablets (150 mg + 250 mg + 90 mg)
Aluminium Hydroxide + Magnesium
Hydroxide + Simethicone
Suspension (8 % + 8 % + 0.8 %)
Aluminium Hydroxide + Magnesium
Hydroxide Chewable Tablets
(200 mg + 200 mg)
Aluminium Hydroxide + Magnesium
Hydroxide Suspension (4 % + 4 %)
Aluminium Hydroxide + Magnesium
Silicate Chewable Tablets
Ambroxol Tablets (30 mg)
Aminophylline Tablets (90 mg)
Aminophylline Tablets (100 mg), I
Aminophylline Tablets (100 mg), II
Amitryptylline Tablets
(10 mg and 25 mg)
Amoxicillin Dry Syrup (5 %)
Amoxicillin Lyophylisate for Injection
(250 mg)
Amoxicillin Tablets (125 mg)
Ampicillin + Cloxacillin Oily
Suspension (1.5 % + 4.0 %)
Ampicillin Dry Syrup (5 %)
Ampicillin Tablets (250 mg)
Ampicillin Tablets (500 mg)
Anise Oil Solution (1%)
Ascorbic acid see Vitamin C
Asparagus Extract + Parsley Extract
Tablets (200 mg + 200 mg)
Aspartame Effervescent Tablets
(20 mg)
Aspartame Tablets (25 mg), DC
Aspartame Tablets (25 mg), WG
Atenolol Tablets (90 mg)
Azithromycin Dry Syrup
(500 mg/10 ml)

BASF Fine Chemicals Generic Drug Formations 1998

Azithromycin Suspension
(500 mg/10 ml)
Azulene solution (1%)
B
Barium Sulfate Oral Suspension (23 %)
Basic Cream for Different Active
Ingredients
Benzhexol Tablets (5 mg)
Benzoyl Peroxide + Alpha-Bisabolol
Gel (5.0 % + 0.2 %)
Benzyl Benzoate Solution (10 %)
Benzylpenicilline + Dihydrostreptomycin Injectable Suspension
(200,000 units + 200 mg/ml)
Berberine Tablets (5 mg)
Beta Carotene + Vitamin C +
Vitamin E Chewable Tablets
(10 mg + 500 mg + 250 mg)
Beta Carotene + Vitamin C + Vitamin
E Tablets
(6 mg + 100 mg + 30 mg)
Beta Carotene + Vitamin C + Vitamin
E Tablets
(7 mg + 60 mg + 15 mg)
Beta Carotene + Vitamin C + Vitamin
E Tablets
(12 mg + 250 mg + 125 mg)
Beta Carotene Effervescent Tablets
(7 mg)
Beta Carotene Tablets (15 mg)
Beta Carotene Tablets (20 mg)
Betamethasone + Neomycin GelCream (0.1% + 0.6 %)
Betamethasone Cream (0.1%)
Betamethasone Gel (0.1%)
Bifonazole Cream (1%)
Bran Tablets (250 mg), DC
Bran Tablets (250 mg), WG
Bromhexine Tablets (8mg)
Bromocriptine Tablet Cores (6 mg)

BASF Fine Chemicals Generic Drug Formulations 1998

C
Calcium Carbonate Tablets (500 mg)
Calcium Effervescent Tablets
(250 mg)
Calcium Gluconate Tablets (350 mg)
Calcium Glycerophosphate Tablets
(200 mg)
Calcium Glycerophosphate Tablets
(500 mg)
Calcium Pantothenate see Vitamin B 5
Calcium Phosphate Tablets for Cats
and Dogs (400 mg)
Captopril Tablets (25 mg)
Carbamazepine Tablets (200 mg)
Carbonyl Iron + Manganese Sulfate +
Copper Sulfate Tablets
(24 mg + 3.5 mg + 0.16 mg)
Carnitine + Coenzym Q Solution
(4.0 % + 0.1%)
Caroate Dispersible Cleaning Tablets
(880 mg)
Caroate Effervescent Cleaning Tablets
(650 mg)
Charcoal Tablets (250 mg)
Chloramphenicol
Ophthalmic Solution (3 %)
Chloramphenicol Palmitate Oral or
Topical Emulsion
(2.5 % = 250 mg/10 ml)
Chloramphenicol Palmitate Oral or
Topical Emulsion
(5.0 % = 500 mg/10 ml)
Chlorhexidine Gel (2 %)
Chlorhexidine Lozenges (5 mg)
Chloroquine Tablets (250 mg)
Choline Theophyllinate Tablets (100 mg)
Chymotrypsine Tablets (27 mg)
Cimetidine Tablets (200 mg)
Cimetidine Tablets (280 mg)
Cimetidine Tablets (400 mg)
Clenbuterol Tablets (20 µg)
Clobazam Tablets (10 mg)
Clomifen Tablets (50 mg)
Closantel Veterinary Injectable
Solution (12 – 20 g/100 ml)
Clotrimazol Topical Solution (3 %)

Clotrimazole Cream (1%)
Crospovidone Effervescent Tablets
(1000 mg)
Crospovidone Water Dispersible
Tablets (1000 mg)
Cyanocobalamin see Vitamin B 12
Cyproheptadine Tablet (4 mg)

Ferrous Sulfate Tablets (200 mg)
Fir Needle Oil Solution (3 %)
Folic Acid Tablets (5 mg)
Fucidine Tablet Cores (125 mg)
Furaltadone Injectable Solution
(50 mg/ml)
Furosemide Tablets (40 mg)
Furosemide Tablets (200 mg)

D
G
Dexpanthenol Gel-Cream (5 %)
Diazepam Injectable Solution
(2.5 mg/ml)
Diazepam Tablet (10 mg)
Diclofenac Gel (1%)
Diclofenac Gel-Cream (1%)
Diclofenac Injectable Solution
(75 mg/3 ml)
Diclofenac Oral Solution (1.5 %)
Diclofenac Tablet Cores (50 mg)
Diclofenac Tablets (50 mg)
Diltiazem Tablets (50 mg)
Dimenhydrinate Tablet Cores
(100 mg)
Dimenhydrinate Tablets (50 mg)
E
Enteric Film Coating
Ephedrine Tablets (100 mg)
Erythromycin Gel (1%)
Ethambutol Tablets (400 mg), DC
Ethambutol Tablets (400 mg), WG
Ethambutol Tablets (800 mg)
Etophylline + Theophylline Tablets
(100 mg + 22 mg), DC
Etophylline + Theophylline Tablets
(100 mg + 22 mg), WG
Eucalyptol Solution (8 %)
F
Famotidine Tablets (40 mg)
Ferrous Fumarate Tablets (200 mg)
Ferrous Sulfate + Manganese Sulfate
+ Copper Sulfate Tablets
(65 mg + 3.5 mg + 0.16 mg)

Garlic Tablets Cores (100 mg)
Glibenclamide Tablets (5 mg)
Glutaminic Acid Tablets (550 mg)
Gramicidin Ophthalmic Solution
(1.3 mg/10 ml)
Griseofulvin Tablets (125 mg)
Griseofulvin Tablets (500 mg)
H
Heparin Gel (30,000 i.u./100 g)
Horsetail Extract Tablets (450 mg)
Hydrochlorothiazide + Potassium
Chloride Tablet Cores
(50 mg + 300 mg)
Hydrochlorothiazide Tablets
(50 mg), DC
Hydrochlorothiazide Tablets
(50 mg), WG
Hydrocortisone Aqueous Gels (1%)
Hydrocortisone Cream (1%)
Hydrocortisone Ethanolic Gel (0.5 %)
I
Ibuprofen Gel-Cream (5 %)
Ibuprofen Gels (5 %)
Ibuprofen Solution (2 %)
Ibuprofen Suspension
(4 % = 400 mg/10 ml), I
Ibuprofen Suspension
(4 % = 400 mg/10 ml), II
Ibuprofen Tablets (400 mg), DC
Ibuprofen Tablets (400 mg), WG
Ibuprofen Tablets for Children
(150 mg)

BASF Fine Chemicals Generic Drug Formulations 1998

Indomethacin Gel (1%), I
Indomethacin Gel (1%), II
Indomethacin Powder for Hard
Gelatin Capsules (160 mg)
Indomethacin Suppositories (50 mg)
Indomethacin Tablets (50 mg), DC
Indomethacin Tablets (50 mg), WG
Indomethacin Tablets (100 mg)
Inosin Tablet Cores (200 mg)
Isosorbide Dinitrate Tablets (5 mg)
K
Khellin Tablets (25 mg)
L
Levamisole Tablets (150 mg)
Levothyroxine Tablets (0.05 g)
Lidocain Gel (2 %)
Lidocain Gel-Cream (5 %)
Lisinopril Tablets (10 mg)
M
Magaldrate Chewable Tablets
(500 mg)
Magaldrate Dispersible Tablets
(700 mg)
Magaldrate Instant Powder or Dry
Syrup
Magaldrate Suspension (10 %)
Magnesium Carbonate Tablets
(260 mg)
Mebendazol Tablets (100 mg)
Mebendazole Suspension
(2 % = 200 mg/10 ml)
Mefenamic Acid Tablets (250 mg)
Meprobamate + Phenobarbital
Tablets (400 mg + 30 mg), DC
Meprobamate + Phenobarbital
Tablets (400 mg + 30 mg), WG
Meprobamate Tablets (400 mg), DC
Meprobamate Tablets (400 mg), WG
Metamizol Tablets (500 mg)
Metformin Tablets (500 mg)

BASF Fine Chemicals Generic Drug Formulations 1998

Methyl Cysteine Tablets (100 mg)
Methyl Salicylate + Menthol Gel
(11% + 5 %)
Metoclopramide Tablets (10 mg)
Metronidazole Effervescent Vaginal
Tablets (500 mg)
Metronidazole Injectable Solution
(500 mg/10 ml)
Metronidazole Tablet Cores (400 mg)
Metronidazole Tablets (200 mg)
Metronidazole Tablets (500 mg)
Metronidazole Vaginal Gel (1.2 %)
Miconazole Cream (2 %)
Miconazole Injectable Solution (1%)
Miconazole Mouth Gel (2 %)
Mint Mouth Wash Solutions
Mint Oil Solution (3.5 %)
Multivitamin + Calcium + Iron + Tablets
Multivitamin + Calcium Syrup
Multivitamin + Carbonyl Iron Tablets
Multivitamin + Minerals Tablets with
Beta Carotene
Multivitamin Chewable Tablets for
Children
Multivitamin Drops
Multivitamin Effervescent Granules
Multivitamin Effervescent Tablets
with Beta Carotene (Food)
Multivitamin Effervescent Tablets (I)
Multivitamin Effervescent Tablets (II)
Multivitamin Injectable for
Veterinary Application
Multivitamin Instant Granules
Multivitamin Oral Gel (vet.)
Multivitamin Oral Gel with Linoleic
Acid and Linolenic Acid
Multivitamin Syrup, I
Multivitamin Syrup, II
Multivitamin Tablets (I)
Multivitamin Tablets (II)
Multivitamin Tablet Cores with
Beta-Carotene
Multivitamin Tablets for Dogs
Multivitamin Tablets with Beta
Carotene
Multivitamin Two Chamber Ampules

N
Nalidixic Acid Tablets (500 mg)
Naproxen Tablets (250 mg)
Naproxen Tablets (450 mg)
Neomycin Gel (0.05 %)
Neomycin Tablets (250 mg)
Nicotinic Acid Tablets (200 mg)
Nicotinamide see Vitamin B 3
Nifedipine Tablet Cores (10 mg)
Nitrendipine Tablets (25 mg)
Nitrofurantoin Tablet Cores (100 mg)
Nitrofurantoin Tablets (100 mg)
Norephedrine Syrup (40 mg/10 g)
Nystatin Suspension (100,000 i.u./ml)
Nystatin Tabet Cores (200 mg)
Nystatin Tablets (50 mg and 100 mg)
O
Omega Fatty Acids Tablet Cores
(10 mg EPA + DNA)
Oxytetracycline Injectable Solution for
Veterinary Application
(500 mg/10 ml)
Oxytetracycline Sustained Release
Injectable for Veterinary Application
(2.2 g/10 ml)
Oxytetracycline Tablets (250 mg)
P
Pancreatin Tablet Cores (30 mg)
Pancreatin Tablet Cores (130 mg)
Pancreatin Tablet Cores (300 mg)
Paracetamol (= Acetaminophen) +
Caffeine Tablets (500 mg + 50 mg)
Paracetamol (= Acetaminophen) +
Doxylamine + Caffeine Effervescent
Granules
(500 mg + 5 mg + 33 mg/2.1 g)
Paracetamol (= Acetaminophen)
Instant Granules
(250 mg or 500 mg)
Paracetamol (= Acetaminophen) +
Ibuprofen + Orphenadin Tablets
(250 mg + 200 mg + 100 mg)

Paracetamol (= Acetaminophen) +
Norephedrine + Phenyltoloxamine
Tablets (300 mg + 25 mg + 22 mg)
Paracetamol (= Acetaminophen) +
Phenprobamat Tablets
(200 mg + 200 mg)
Paracetamol (= Acetaminophen)
Chewable Tablets (300 mg)
Paracetamol (= Acetaminophen)
Effervescent Tablets (500 mg)
Paracetamol (= Acetaminophen)
Instant Granules (500 mg)
Paracetamol (= Acetaminophen)
Suppositories (150 mg and 500 mg)
Paracetamol (= Acetaminophen)
Suspension (5 % = 500 mg/10 ml)
Paracetamol (= Acetaminophen)
Syrup (5 % = 500 mg/10 g)
Paracetamol (= Acetaminophen)
Syrup for Children
(2.5 % = 250 mg/10 ml)
Paracetamol (= Acetaminophen)
Tablet Cores (500 mg)
Paracetamol (= Acetaminophen)
Tablets (500 mg)
Paracetamol (= Acetaminophen)
Tablets for Children (200 mg)
Phendimetrazin Tablets (35 mg)
Phenindion Tablets (50 mg)
Phenolphthalein Tablet Cores (200 mg)
Phenytoin Oral Suspension (5 %)
Phenytoin Sodium Tablets (100 mg),
DC
Phenytoin Sodium Tablets (100 mg),
WG
Phenytoin Tablets (100 mg)
Piroxicam + Dexpanthenol Gel
(0.5 % + 5.0 %)
Piroxicam Water Dispersible Tablets
(20 mg)
Placebo Tablets
Polidocanol Wound Spray
Povidone-Iodine + Lidocain Gel (10 %)
Povidone-Iodine Bar Soap (5 %)
Povidone-Iodine Bar Soaps (5 %)
Povidone-Iodine Concentrates for
Broilers and Cattles (20 %)

BASF Fine Chemicals Generic Drug Formulations 1998

Povidone-Iodine Cream (10 %)
Povidone-Iodine Effervescent Vaginal
Tablets (350 mg)
Povidone-Iodine Foam Spray (10 %)
Povidone-Iodine Gargle Solution
Concentrate (10 %)
Povidone-Iodine Gel-Cream (10 %)
Povidone-Iodine Gels (10 %)
Povidone-Iodine Glucose Ointment
(2.5 %(
Povidone-Iodine Lipstick or After
Shave Stick (10 %)
Povidone-Iodine Liquid Spray (10 %)
Povidone-Iodine Lozenges (5 mg)
Povidone-Iodine Mastitis Cream (10 %)
Povidone-Iodine Mouth Wash and
Gargle Solution Concentrate
(7.5 %)
Povidone-Iodine Ophthalmic
Solutions (0.4 %)
Povidone-Iodine Ophthalmic
Solutions (1.0 %)
Povidone-Iodine Powder Spray
Povidone-Iodine Pump Spray (1%)
Povidone-Iodine Seamless Solutions
(10 %)
Povidone-Iodine Shampoo (7.5 %)
Povidone-Iodine Soft Gel (1%)
Povidone-Iodine Solution (10 %), I
Povidone-Iodine Solution (10 %), II
Povidone-Iodine Surgical Scrubs
(7.5 %), I
Povidone-Iodine Surgical Scrubs
(7.5 %), II
Povidone-Iodine Teat-Dip Solution
(3 %)
Povidone-Iodine Transparent
Ointment (10 %)
Povidone-Iodine Vaginal Douche
Concentrate (10 %)
Povidone-Iodine Vaginal Ovula (5 %)
Povidone-Iodine Vaginal Ovula (10 %)
Povidone-Iodine Viscous Solution
(1%)
Prazosin Tablets (5 mg)
Prednisolone Tablets (20 mg)
Prednisone Tablets (10 mg)

BASF Fine Chemicals Generic Drug Formulations 1998

Probenecid Tablets (500 mg)
Procain Penicillin Injectable
Suspension (300 mg/ml)
Propanidide Injectable Solution
(50 mg/ml)
Propranolol Hydrochloride Tablets
(10 mg, 50 mg and 100 mg)
Propranolol Tablets Cores (40 mg)
Protective Film Coating with
Ethylcellulose + Kollidon VA 64
Protective Film Coating with HPC
+ Kollidon VA 64
Protective Film Coating with HPMC
+ Kollidon VA 64
Protective Film Coating with Kollidon
VA 64
Protecitive Filmcoating with Polyvinyl
Alcohol + Kollidon VA 64
Protective Film Coating with Shellac
+ Kollidon 30
Pseudoephedrine Tablets (60 mg)
Pyrazinamide Tablets (500 mg), DC
Pyrazinamide Tablets (500 mg), WG
Pyridoxine see Vitamin B 6
R
Ranitidine Tablet Cores (150 mg)
Ranitidine Tablet Cores (300 mg)
Riboflavin see Vitamin B 2
Rifampicin Tablets (450 mg)
S
Saccharin Effervescent Tablets
(15 mg)
Saccharin Tablets (15 mg)
Selegiline Tablets (5 mg)
Serratio Peptidase Tablets (10 mg)
Silimarin Tablets (35 mg)
Simethicone Chewable Tablets
(70 mg)
Simethicone Chewable Tablets
(80 mg)
Simethicone Instant Granules (6 %)
Sobrerol Injectable Solution
(75 mg/5 ml)

Sodium Fluoride Tablets (0.5 mg)
Sodium Fluoride Tablets (1.3 mg)
Spironolactone Tablets (25 mg)
Spirulina Extract Chewable Tablets
(250 mg)
Subcoating of tablets Cores
Sucralfate Tablets (500 mg)
Sugar Coating, automatic
Sugar Coating, manual
Sugar Film Coating
Sulfadiazine + Trimethoprim
Veterinary Oral Suspension
(40 % + 8 %)
Sulfadiazine Tablets (450 mg)
Sulfadimethoxine Veterinary Injectable
Solution (250 mg/10 ml)
Sulfadimidine Tablets (500 mg)
Sulfadoxine + Trimethoprim Veterinary
Injectable Solution
(1000 mg + 200 mg/10 ml)
Sulfadoxine Solution (2 % = 20 mg/ml)
Sulfamethoxazole + Trimethoprim
Tablets (400 mg + 80 mg)
Sulfamethoxazole + Trimethoprim Dry
Syrup (400 mg + 80 g/10 ml)
Sulfamethoxazole + Trimethoprim
Oral Suspension
(400 mg + 80 mg/5 ml)
Sulfamoxole + Trimethoprim
Veterinary Injectable Solution
(400 mg + 80 mg/10 ml)
Sulfathiazole Tablets (250 mg)
Sulfathiazole Veterinary Injectable
Solution (8 mg/ml)
Sulfathiazole Veterinary Oral Solution
(8 mg/ml)
T
Tannin-Crospovidone Complex
Tablets (55 mg + 230 mg)
Terazosin Tablets (1 mg and 5 mg)
Terfenadine Suspension
(60 mg/5 ml = 1.2 %)
Terfenadine Tablets (60 mg)
Tetracycline Tablets (125 mg)

Tetracycline Tablets (250 mg)
Tetrazepam Tablets (50 mg)
Theophylline + Ephedrine Tablets
(130 mg + 15 mg)
Theophylline Tablets (100 mg)
Theophylline Injectable Solution
(200 mg/5 ml)
Thiamine see Vitamin B 1
Tretinoin + Alpha Bisabolol Gel
(50 mg + 100 mg/100 g)
Tretinoin + Dexpanthenol Gel
(50 mg + 2.5 g/100 g)
Tretinoin Cream (50 mg/100 g)
Tretinoin Gel (50 mg/100 g)
Tretinoin Solution (50 mg/100 g)
Triamcinolone Tablets (4 mg)
Trifluoperazine Tablets (5 mg)
Trihexylphenidyl see Benzhexol
U
Ultrasonic Adhesive Gel
V
Valeriana Extract + Passiflora Extract
Tablet Cores (44 mg + 30 mg)
Valproate Sodium Tablets (500 mg)
Verapamil Tablets (120 mg)
Vitamin A + Vitamin B 6 + Vitamin E
Tablets (40,000 i.u. + 40 mg
+ 35 mg)
Vitamin A + Vitamin C + Vitamin D 3
Chewable Tablets for Children
(2,000 i.u. + 30 mg + 200 i.u.)
Vitamin A + Vitamin C + Vitamin E
Tablets (1,200 i.u. + 60 mg +
30 mg)
Vitamin A + Vitamin D 3 + Calcium +
Magnesium Injectable Solution
(33,000 i.u. + 6,000 i. u. +
100 mg + 200 mg/g)
Vitamin A + Vitamin D 3 + Vitamin E +
Beta Carotene Veterinary Injectable
Solution (100,000 i.u. + 20,000 i.u.
+ 10 mg + 8 mg/g)

BASF Fine Chemicals Generic Drug Formulations 1998

Vitamin A + Vitamin D 3 + Vitamin E
Aqueous Injectable Emulsion for
Cattles (500,000 i.u. + 75,000 i.u.
+ 50 mg/ml with Solutol HS 15)
Vitamin A + Vitamin D 3 + Vitamin E
Aqueous Injectable Emulsion for
Cattles (500,000 i.u. + 75,000 i.u.
+ 50 mg/ml with Cremophor EL)
Vitamin A + Vitamin D 3 + Vitamin E
Concentrates, Water-miscible
(120,000 i.u. + 60,000 i.u. +
40 mg/ml)
Vitamin A + Vitamin D 3 + Vitamin E
Injectable Solution in Organic
Solvents for Cattles (500,000 i.u.
+ 75,000 i.u. + 50 mg/ml)
Vitamin A + Vitamin D 3 + Vitamin E
Veterinary Injectable Solution
(100,000 i.u. + 20,000 i.u.
+ 10 mg/g)
Vitamin A + Vitamin D 3 Concentrate,
Water-miscible (100,000 i. u.
+ 20,000 i. u./ml)
Vitamin A + Vitamin D 3 Concentrate,
Water-miscible (120,000 i. u.
+ 12,000 i.u./g)
Vitamin A + Vitamin D 3 Drops
(30,000 i.u. + 3,000 i.u./g)
Vitamin A + Vitamin D 3 Injectable
Solutions (30,000 i.u. + 5,000 or
10,000 i.u./ml)
Vitamin A + Vitamin D 3 Oral Solution
for Children (1,000 i.u. + 100 i.u./ml)
Vitamin A + Vitamin D 3 Syrup
(30,000 i.u. + 10,000 i.u./ml)
Vitamin A + Vitamin E Chewable
Tablets (30,000 i.u. + 35 mg)
Vitamin A + Vitamin E Drops
(25,000 i. u. + 50 mg/ml)
Vitamin A + Vitamin E Drops
(5,000 i.u. + 50 mg/ml)
Vitamin A + Vitamin E Injectable
Solution for Sheeps (250,000 i.u.
+ 25 mg/ml)
Vitamin A + Vitamin E Tablets
(33,000 i.u. + 70 mg)

BASF Fine Chemicals Generic Drug Formulations 1998

Vitamin A Chewable Tablets
(100,000 i.u.)
Vitamin A Concentrate, Water-miscible
(100,000 i. u./ml)
Vitamin A Drops (50,000 i. u./ml)
Vitamin A Ethanolic Veterinary
Injectable Solution (500,000 i.u./ml)
Vitamin A Suppositories (150,000 i.u.)
Vitamin A Tablet Cores (50,000 i.u.)
Vitamin A Tablets (25,000 i.u.)
Vitamin A Tablets (50,000 i.u.)
Vitamin B Complex + Amino Acid +
Magnesium Effervescent Granules
Vitamin B Complex + Carnitine Tablet
Cores
Vitamin B Complex + Minerals +
Linoleic/Linolenic Acid Syrup
Vitamin B Complex + Vitamin C +
Calcium Effervescent Tablets
Vitamin B Complex + Vitamin C +
Ferrous Sulfate Tablets
Vitamin B Complex + Vitamin C
Effervescent Tablets
Vitamin B Complex + Vitamin C
Instant Granules
Vitamin B Complex + Vitamin C
Syrup, I
Vitamin B Complex + Vitamin C
Syrup, II
Vitamin B Complex + Vitamin C
Tablets
Vitamin B Complex Injectable Solution
Vitamin B Complex Syrup
Vitamin B Complex Tablets I
Vitamin B Complex Tablets II
Vitamin B 1 + Caffeine Tablets
(500 mg + 100 mg)
Vitamin B 1 + Vitamin B 2 + Vitamin B 3
+ Vitamin B6 Injectable Solution
(100 mg + 6 mg + 40 mg + 4 mg/2
ml)
Vitamin B 1 + Vitamin B 6 + Vitamin B 12
Tablets (100 mg + 10 mg + 100 µg)
Vitamin B 1 + Vitamin B 6 + Vitamin B 12
Tablets
(100 mg + 200 mg + 100 µg)

01% = 1 mg/10 ml) Vitamin E Tablets (50 mg) Vitamin K 1 Phytomenadion) Injectable Solution (10 mg and 20 mg/ml) BASF Fine Chemicals Generic Drug Formulations 1998 . 500 mg. 1. WG Vitamin B 1 Tablets (300 mg) Vitamin B 12 Tablets.Vitamin B 1 + Vitamin B 6 + Vitamin B12 Tablets (250 mg + 250 mg + 1 mg) Vitamin B 1 Tablets (50 mg). I Vitamin B 1 Tablets (50 mg). DC Vitamin B 6 Tablets (40 mg).000 mg) Vitamin C Chewable Tablets (500 mg) Vitamin C Chewable Tablets with Dextrose (100 mg) Vitamin C Chewable Tablets with Fructose (120 mg) Vitamin C Chewable Tablets with Sucrose (500 mg) Vitamin C Effervescent Tablets (100 mg and 1000 mg) Vitamin C Effervescent Tablets (500 mg) Vitamin C Tablets (100 mg) Vitamin C Tablets (200 mg) Vitamin C Tablets (250 mg) Vitamin C Tablets (400 mg) Vitamin E + Benzocaine Solution (5 % + 2 %) Vitamin E + Selenium Veterinary Injectable Solution (60 mg E + 3 mg Se/ml) Vitamin E Chewable Tablets (100 mg) Vitamin E Chewable Tablets (150 mg) Vitamin E Chewable Tablets (200 mg) Vitamin E Chewable Tablets (400 mg) Vitamin E Concentrate. Water-miscible (10 % = 100 mg/ml) Vitamin E Drops (50 mg/ml) Vitamin E Gel-Cream (10 %) Vitamin E Solution with Ethanol (0. Coloured (50 µg) Vitamin B 2 Tablets (3 mg) Vitamin B 2 Tablets (10 mg) Vitamin B 2 Tablets (75 mg) Vitamin B 2 Tablets (100 mg) Vitamin B 2 Tablets (150 mg) Vitamin B 3 (Nicotinamide) Tablets (300 mg) Vitamin B 5 (Calcium D-Pantothenate) Chewable Tablets (600 mg) Vitamin B 5 (Calcium D-Pantothenate) Tablets (100 mg) Vitamin B 5 (Calcium D-Pantothenate) Tablets (280 mg) Vitamin B 5 (Calcium D-Pantothenate) Tablets (300 mg) Vitamin B 6 Tablets (40 mg). WG Vitamin B 6 Tablets (100 mg) Vitamin B 6 Tablets (250mg) Vitamin B 6 Tablets (300 mg) Vitamin C + Calcium Carbonate Effervescent Tablets (500 mg + 300 mg) Vitamin C + Vitamin E Lozenges (100 mg + 50 mg) Vitamin C Chewable Tablets (100 mg. II Vitamin B 1 Tablets (100 mg). DC Vitamin B 1 Tablets (100 mg).

as necessary. For this reason. 1.5 Excipients As far as possible. Thus. The serial numbers in the left-hand column of this table are quoted in the formulations. but has a different grain size or originates from another manufacturer. Significant differences in the properties of the preparations may occur if the same active substance is used.3 Size and optimization of the formulations All the formulations were developed exclusively on a laboratory scale of the order of 1 kg maximum. Since the manufacturer’s name was mostly not mentioned. Chapter 2. 1.4 Active substances The active substances are almost exclusively generic. The excipients mostly used in the formulations and their suppliers are listed in Table 1. They were mostly supplied free of charge as samples by pharmaceutical companies. scale-up for production must therefore be checked and revised.5). The reason for this is that the difference in physical properties may exert a strong effect particularly on solid drugs (cf. the manufacturer’s name and the registered trademark are given for excipients. It is only in very exceptional cases that the formulations have been optimized by a systematic study involving a comparison between different excipients or by varying the amounts of excipients.1. it unfortunately cannot be listed here. BASF Fine Chemicals Generic Drug Formulations 1998 . the formulations are merely suggestions that require further optimization.

powder Mallincrodt Inc. Food + Pharmaceutical Products 735 Market Street Philadelphia. USA Stearic acid Meggle Milchindustrie GmbH Postfach 40 83512 Wasserburg.O. Germany Aerosil® 200 FMC Corp. Germany Potato starch Corn starch Degussa AG GB Industry + Fine Chemicals Postfach 1345 63457 Hanau.Table 1 Supplier and address Excipients [1] or BASF subsidiary in the country concerned Cremophor® products Kollicoat ® products Kollidon® products Ludipress ® Lutrol ® products Propylene glycol Pharma Sicovit ® Soluphor® P Solutol ® HS 15 [2] Bärlocher GmbH 80992 Munich. Louis. Germany Lactose Monohydrate D 20 Tablettose ® [4] [5] [6] [7] [8] BASF AG Department MER 67056 Ludwigshafen. Box 5439 675 McDonnel Boulevard St. MO 63134. PA 19103. Germany Polyethylene glycol 6000. P. USA Avicel ® products Ac-Di-Sol ® Hüls AG Postfach 45674 Marl. Germany BASF Fine Chemicals Generic Drug Formulations 1998 . Germany Calcium arachinate Magnesium stearate [3] Cerestar GmbH Düsseldorferstrasse 191 47809 Krefeld.

CaHPO 4 France (DITAB ®) [10] Riedel-de-Haen AG Wunstdorferstrasse 40 30926 Seelze. Rue Pierre Pays B. 52 69660 Collonges-au Mont d’Or. Germany Sorbitol.[9] Rhône-Poulenc 15. crystalline Talc BASF Fine Chemicals Generic Drug Formulations 1998 . Dicalcium phosphate.P.

Aromas or colorants are added to the formulations in amounts depending on the particular taste of the target group. Data on the chemical stability are often available for sensitive materials. data are also listed on the physical stability. e. a. b.1. The reasons are as follows. They mostly concern either storage at room temperature (20 – 25 °C) over a period of one year or a stress test that lasts at least just as long. c. PVP-iodine or vitamins. In view of the very number of formulations presented here and for capacity reasons. In a number of formulations. The stability of the preparation may change as a result of items a. and b. Thus the final formulation must be checked in any event. BASF Fine Chemicals Generic Drug Formulations 1998 . g.6 Stability data It is only in exceptional cases or when certain groups of active substances are present that data are given on the chemical and/or the physical stability of the formulations. the long-term stability of all of them cannot be checked. The formulations are practically always modified by the customer when they are scaled up to meet the demands of industry.

1 Size of formulations and measured values The formulations were developed on a laboratory scale in which case 200 –1. g. It thus combines the properties of a filler. By virtue of its versatility formulations containing it are usually very simple. Ludipress.2 Tablets 2. and a disintegrant. This combination even allows 500 mg of paracetamol to be pressed into good tablets with a weight of 700 mg. g. e. hardness. disintegrant. binder. B. particularly in the production of generics. behave very differently with Ludipress when the dosage is extremely high. The beneficial properties of Kollidon VA 64 can BASF Fine Chemicals Generic Drug Formulations 1998 . or starch. and flowability agent and also often acts as a release accelerator. Two important alternatives. 2. that the active substance permits.5). and chipping of the tablets and the data on their release are measured values. Even substances such as ascorbic acid that are hardly suitable for direct tabletting owing to the friability of their crystals can normally be directly pressed into tablets at concentrations of 30 – 40 %. is an important parameter in direct compression. g. Kollidon VA 64 An alternative to Ludipress is the outstanding dry binder Kollidon VA 64 together with excipients. this technique is not as suitable if the content of ascorbic acid is higher. Plasticity. many analgetics. It can also be combined with almost all active substances with the exception of those that enter into a chemical interaction with lactose (Maillard reaction). this property of Kollidon VA 64 is not adversely effected by increasing the pressure.2 Direct compression The technology involved in direct compression assumes great importance in the tablet formulations. in particular. viz. The limiting factors are the physical properties of the active substance and its concentration in the tablets (cf. Kollidon 30. and Kollidon CL.000 g of the mixtures to be tabletted were used. the amounts weighed out in the formulations correspond to the amount in the tablets multiplied by a factor of 1. A. Normally. e. can be found in the BASF line of pharmaceutical excipients for direct compression. As can be seen in Fig. g. and the fraction of Ludipress required in the tablets is too large for paracetamol (= acetaminophen). Acetylsalicylic acid and metamizole can be pressed when little Ludipress has been added. because it is often the cheapest means. microcrystalline cellulose. disintegration. Active substances. e. However. ibuprofen requires a larger amount. Ludipress and Kollidon VA 64. Chapter 2. calcium phosphate. Kollidon CL. e. lactose. 1. Ludipress Ludipress is a speciality derived from lactose. No other dry binder has a binding power and plasticity comparable to those of Kollidon VA 64. The weight.000. This limit may be shifted upwards by special direct compression auxiliaries.

g. Fluidized-bed granulation was resorted to only in exceptional cases in view of the amounts needed.5 0. eliminates all problems in wet granulation. i. – granulation with a Kollidon solution – granulation of a dry mixture of the active substance and (filler and) Kollidon with water/solvent – granulation in which some of the Kollidon is mixed with the active substance and the rest is dissolved in the solution used for granulation 2.7 0.3 Wet granulation Great significance is still attached to wet granulation.4 Kollidon VA 64 Kollidon 30 Mc. moistening. Other alternatives consist of using different grades of Kollidon. The example of a placebo tablet illustrated in Fig. because direct compressing is not the most suitable technology for many active substances that are in high dosages or in fine powder form.Plasticity 1. Substituting Kollidon 25 or Kollidon 30 by Kollidon 90 F would be particularly interesting for obtaining greater hardness without increasing the pressure.5 % binder + 0. in a fluidized bed. BASF Fine Chemicals Generic Drug Formulations 1998 The last the of the three alternatives is preferred if the amount of liquid required for granulation is restricted and therefore the viscosity of the solution containing all of the Kollidon would be too high. modern equipment. 2 shows that tablets of twice the hard- . Cellulose HPMC 11000 Plasticity = plastic energy/total energy Fig. screening. The granules for tabletting of the presented formulations were mostly produced by traditional means. e.8 0. drying. Various alternatives to wet granulation in general are offered by BASF pharmaceutical excipients: Obviously.6 0.0 Force: 18 kN Force: 25 kN 0. and again screening. e. Even if the active substance is sensitive to hydrolysis.5 % magnesium stearate) also be exploited for the production of concentrated active substance that is subsequently used for direct tabletting. 1 Plasticity of dry binders in tablets (99.9 0. Kollidon VA 64 and Ludipress can also be combined with one another.

In practice. there would be some point in changing over from Kollidon 90 F to Kollidon 25 or 30 if the viscosity of the solution used in granulation is too high. Tablet Hardness (N) Conversely. 2 Hardness of lactose tablets containing various Kollidon products (wet granulation) ness of those obtained by Kollidon 25 can be achieved by using Kollidon 90 F at low pressures. 3 Direct compression of different types of ascorbic acid (40 % ascorbic acid. 5 % Kollidon VA 64) BASF Fine Chemicals Generic Drug Formulations 1998 .4 Tablet press All the formulations were devised on rotary tabletting presses that were fitted with 10 – 20 punches. the same hardness is usually achieved by increasing the amount of Kollidon. 2. however.5 Effect of the physical properties of the active substance In the manufacture of tablets it is important to define and appreciate the 140 120 100 80 60 40 crystalline grade Compression force: 25 kN powder grade Fig. 2.Hardness N Kollidon 25 Kollidon 30 Kollidon 90 F 90 80 70 60 50 40 4 6 8 10 12 Compression force kN 14 16 Fig.

2..5 mg mg mg mg mg Tablet properties Binder Hardness Disintegration time Dissolution (30 min) Povidone K 90 95 % > 250 µm 66 N 18 min 23 % Povidone K 90 15 % > 250 µm 97 N 22 min 19 % BASF Fine Chemicals Generic Drug Formulations 1998 ...5 Water .6 Effect of the physical properties of the excipients Characterization of the physical properties of excipients is also important... This is demonstrated in Table 2 in the light of the example of hydrochlorothiazide....... these data cannot be given for all formulations.... 3 shows the difference that can occur when ascorbic acid tablets of the same composition are produced at the same pressure.5 Magnesium stearate .. 37.. This particularly concerns the particle size. but when the active substance consists of crystals of two different sizes (crystalline = > 150 µm....... Fig........ If it is not stated to the contrary.. powder = < 150 µm).....physical properties of the active substance. the disintegration time is measured in artificial gastric juice.. 7..Eur....... 422.... or USP)......7 Methods of measuring the properties of tablets The general instructions for the determination of the corresponding properties of tablets are contained in the Pharmacopoeiae (Ph..8 Information on dissolution of active substance Nowadays it is standard practice and/ or laid down that the in-vitro release of active substance be checked.. 50. 2....... Unfortunately.... 2.0 Povidone K 90 . The release is determined by the methods laid down in the corresponding monographs for the tablets (usually USP) and in the prescribed medium........... the disintegration and the release are also affected... 2.... This is particularly the case when the active substance is sufficiently soluble or when the formulation was developed Table 2 Influence of the particle size of Povidone K 90 on the properties of hydrochlorothiazide tablets (solvent granulation) Formulation I II III Hydrochlorothiazide .............. To a certain extent....... Tablets of greater hardness are obtained if fine instead of coarse Povidone K 90 is taken..5 Lactose monohydrate ....

9 Formulations The formulations in this chapter have been arranged in the alphabetic order of their active substances. BASF Fine Chemicals Generic Drug Formulations 1998 .in a time when this parameter was not yet demanded. 2.

3.3 Conditions for spraying Whenever they are of importance.2 Equipment The tests were mostly performed in the Accela-Cota 241. 1 kg of spray solution or spray suspension and 5 kg of tablet cores. .1 Size of formulations and amounts used The formulations were developed on a laboratory scale. BASF Fine Chemicals Generic Drug Formulations 1998 3. 3. for which the minimum amount of cores is 5 kg. the conditions for processing the formulations on a given scale have been quoted. these two are interchangeable.5 Formulations The formulations in this chapter have been arranged in the alphabetic order of their function. To a certain extent. The batches usually consisted of ca. In a few cases.3 Coating of tablets and capsules 3. the fluidized-bed granulator WSG Glatt 15 or a traditional coating pan was used.4 Colour additives Normally the colorants added were Sicovit colour lakes or Sicovit pigments. 3.

4 Formulations The formulations in this chapter have been arranged in alphabetical order of their active substances. 4.3 Assessment of the properties of the granules Most of the cases concerned granules that were suspended in water before the administration.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. e. in fluidized-bed granulation.4 Granules. screening. were only resorted to in exceptional cases. Normally the amounts used were those required for a trial of 50 – 500 g. i. BASF Fine Chemicals Generic Drug Formulations 1998 . The parameters that attracted most attention were the relative sediment volume (volume of sediment/total volume) and the redispersability. See Chapter 5. Fluidized-bed granulation was resorted to only in exceptional cases in view of the amounts needed. and again screening.3 for details on the suspensions. 4. drying. dry syrups and lyophilisates 4. powders. the properties of the suspension thus formed were assessed. 4.g. moistening. Larger batches. Consequently.e.2 Methods of granulation The granules were mostly produced by traditional means.

The mechanism is probably based. Micelle formation is certainly of minor significance. e. This may be affected by the molecular weight.2 Solubilization of insoluble active substances In order to solubilize insoluble lypophilic or hydrophobic active substances in an aqueous medium. 5.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. The batches were of 50 –1. Cremophor EL.3 Stabilizing suspensions Various BASF pharmaceutical excipients with different functions can be used for stabilizing suspensions. antimycotics of the miconazole type. BASF Fine Chemicals Generic Drug Formulations 1998 . BASF Pharmaceutical Excipients offer several possibilities and mechanisms. for the most part. and Solutol HS 15 act as surfaceactive solubilizers in water and form the structures of micelles. and etherian oils or fragrances.g. A Microemulsions Cremophor RH 40. if it exists at all. Solutol HS 15 is recommended for parenteral use of this solubilizing system and has been specially developed for this purpose. C Hydrophilization Typical fields of application are oilsoluble vitamins. Details are given in the book “Kollidon – Polyvinylpyrrolidone for the pharmaceutical industry”. on the principle of hydrophilization. and clear solutions in water are thus obtained. and there is also a restriction on the amount to be used for each dose administered in intramuscular application. the stronger is the solubility effect and thus the greater the solubility that can be obtained by the active substance. There are also restrictions on the use of this auxiliary in human parenterals. The micelle that envelops the active substance is so small that it is invisible or perhaps visible in the form of an opalescence.000 g size. 5. mouth disinfectants. hexiditin. B Formation of complexing compounds The soluble Kollidon products form reversible complexes with many hydrophobic active substances. In practice.5 Liquid preparations 5. this effect was mostly exploited for the solubilization of antibiotics in human and veterinary medicine. The longer the chains or the higher the K-value of the Kollidon type. Active substances can also be solubilized by Lutrol F 68 in addition to the Cremophor and Kollidon products. It is laid down in many countries that the K-value must not exceed 18.

Kollidon 30 is also used for this purpose.g. of Kollidon 90 F suffice to stabilize aqueous suspensions.5. Kollidon CL-M The use of Kollidon CL-M as a suspension stabilizer has nothing whatever to do with the principle of increasing the viscosity. in particular. Soluble Kollidon products Low concentrations.e. It can be combined with all conventional suspension stabilizers (thickeners. but strongly reduces the rate of sedimentation and facilitates the redispersability. a number of formulations for made-up suspensions or extemporaneous suspensions produced from instant granules or dry syrups 100 50 0 without Povidone with 5% Kollidon 90 F Fig. surfactants. A. B.). an effect that is consistent with the low viscosity. etc.3. The addition of 5 – 9 % has practically no effect in changing the viscosity. which undergoes hardly any sedimentation. One of the reasons for this Kollidon CL-M effect is its low (bulk) density. i.5 % in water) BASF Fine Chemicals Generic Drug Formulations 1998 . It can clearly be seen from Fig. e. % In this book. 2 – 5 %. The example taken was a crospovidone suspension. Fig. Kollidon CL. Relative sediment volume (24 h). A combination consisting of 2 % of Kollidon 90 F and 5 – 9 % of Kollidon CL-M has proved to be an effective system for stabilizing suspensions. 4 demonstrates that it can completely prevent sedimentation. 4 Effect of Kollidon 90 F on the volume of sediment in a crospovidone suspension (7.1 Oral and topical suspensions The following groups of products can be offered for stabilizing oral and topical suspensions. which is only half of that of conventional crospovidone. 5 that a relative volume of sediment of normal micronized crospovidone of high bulk density (= Crospovidone M) is less and more compact that of Kollidon CL-M.

They can be included in the formulations if this is wished.5 % in water + 5 % Lutrol F 127) (see Chapter 4) illustrate the use of Kollidon CL-M. Solutol HS 15 can also be used. penicillin ampoules. 5 Volume of sediment of various micronized crospovidone types (7. preservatives have been already integrated in the formulations. 5. offer a further opportunity of stabilizing suspensions. BASF Fine Chemicals Generic Drug Formulations 1998 5.4.5 Preservation In a few cases. e. bacteria-free or low-bacteria production. should be the subject of accurate research. Lutrol F 68 and Lutrol F 127.g.g.. in the amounts used for this purpose.3. in concentrations of 2 – 5 %. It reduces the sedimentation rate and improves the dispersability. the preservative system i.2 Parenteral suspensions Kollidon 17 PF is eminently suitable for improving the wetability of the active substance in parenteral suspensions. The polyoxamers.Relative sediment volume after (24 h). They also do not increase the viscosity when used in these amounts and can be combined with all other conventional suspension stabilizers. . 5. Kollidon 17 PF. exerts practically no influence on the viscosity. antiacid suspensions with a pH more than 7.e. 5. expressed in terms of the final weight of the suspension. In difficult cases. e. % 100 80 60 40 20 0 Kollidon CL-M Crospovidone M Fig.3. Examples are given in Chapter 3.4 Aromas and dyes Aromas and dyes are quoted in only exceptional cases.3 Dispersions for tablet coating C Lutrol F products Kollidon 25 or Kollidon 30 are particularly suitable for stabilizing pigment suspensions. because they depend strongly on the taste of the target group concerned and are often specific for a particular country.

6 Physical stability The most important parameters for the physical stability of suspensions are the relative volume of sediment (= volume of sediment/total volume) and the redispersability. A stress test was almost always performed for PVP-iodine preparations. They are tested after 1 – 4 weeks have elapsed.5. 5. and this corresponds to at least one year at room temperature.8 Formulations The formulations mentioned in this chapter are arranged in alphabetical order of their active substances. 5. BASF Fine Chemicals Generic Drug Formulations 1998 .7 Chemical stability Data on the chemical stability at room temperature have been compiled almost exclusively for vitamins.

the 2500 2000 Gel 1500 1000 500 0 10 15 20 Liquid 25 30 35 40 45 50 55 60 65 70 75 80 85 90 Temperature. Cremophor A 6 and Cremophor A 25 are the most suitable in the BASF line of excipients for the development of macroemulsions with the appearance and the In the formulations presented here. gels are growing in importance in the pharmaceutical industry. in contrast to pastes and creams. Lutrol E 1500. are intended as water-soluble base for suppositories and ovula. Lutrol E 4000. it can be visually ascertained that the active substance is dissolved. C Fig.2 Emulsifying agents in pharmaceutical creams Rel.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. Lutrol E 400. The size of the batch was usually 100 g.3 Excipients as a base for suppositories and ovula 6. mixtures of the polyethylene glycols. 250 rpm) BASF Fine Chemicals Generic Drug Formulations 1998 . The BASF line of pharmaceutical excipients includes a gel former.4 Gel formers At the present time. and Lutrol E 6000. suppositories and ovula) consistency of a cream. viz.6 Semi-solid drugs (gels. 6 Influence of the temperature on the consistency of 20 % Lutrol F 127 in water (rotary viscometer. with the result that care must be exercised in scaling up from a laboratory to a production scale. creams. They allow the production of physically stable formulations when they are used in low concentrations in the vicinity of 1 – 4 %. This is often coupled with a guarantee of superior absorption. 6. 6. deg. 6. because. viscosity [mPa·s] The Cremophor types.

For the gels based on Lutrol F 127 the addition of 0. in which case a stress test was always performed whose results represent a period of much more than 12 months at room temperature (20 – 25 °C).5 Preservatives and fragrances 6. was mainly determined on creams. The physical stability.2 % sorbic acid is recommended. BASF Fine Chemicals Generic Drug Formulations 1998 . a gel reversibly exists whose consistency depends on the concentration of the Lutrol F 127. No neutralization whatever is necessary.polyoxamer Lutrol F 127. 6. below 15 °C and at temperatures above 75 °C. 6 that the gels are liquid at low temperatures i.6 Stability 6. this point must be worked out in the final formulation. A feature of these gels is their thermoreversible consistency. Consequently. In between these two values. on applying heat at 45 °C. It is apparent from Fig.7 Formulations Preservatives and fragrances were not always added.e. It allows the production of gels whose structures are stable in a pH range of 4 – 8. The formulations given in this chapter have been arranged in alphabetical order of their active substances. Data on the chemical stability are scanty. Preparations with PVP-iodine as disinfectant are an exception.

. Maintain cool until the air bubbles escaped..........19............9 Lutrol E 400 [1].5 Miglyol ® 812 (Dynamit-Nobel)............9 II..0 III..9 Tablet formulations (Lab Scale) Aceclofenac Gel-Cream (1.............. Aceclofenac ....2........ Water..................5 %) 1..... 3..... BASF Fine Chemicals Generic Drug Formulations 1998 ........ Formulation I................. Manufacturing Mix the components I with water and cool to about 5 °C............. Lutrol F 127 [1] ...1.......9...7 g g g g g 2.. firm gel was obtained...4................................................64... Properties of the gel A milky..... Add slowly Lutrol F 127 and continue stirring until Lutrol F 127 is dissolved...........

.......................... 3.. Fill 3..........85............... dry syrups and Iyophylisates (Lab scale) Aceclofenac Instant Granules (50 mg) 1............4 Formulation of granules.... water dispersible granules having almost no bitter taste................1.... Aceclofenac ... Formulation (granules) I.........4...4....... II.. Properties of the granules Free flowing.9 g in sachets corresponding to 50 mg aceclofenac..4 Cremophor RH 40 [1] ..........................................4 Water ....3 Orange flavour ....4......4.............................6 Lutrol F 68 [1]...8 mm screen............... dry and sieve again.... BASF Fine Chemicals Generic Drug Formulations 1998 ............. Manufacturing Granulate mixture I with solution II.... pass through a 0...................about 50 g g g g g g 2................3 Sorbit ....

...7 % 4.... Manufacturing (Wet granulation) Granulate mixture I with solution II..............................................12 mm Hardness........ III....................................................................4 min Friability................0..........250 g Caffeine (Knoll) ........ dry and sieve through a 0..biplanar Diameter .............50 g Isopropanol ..............5 g Kollidon CL [1]......................................9 Tablet formulations (Lab Scale) Acetylsalicylic Acid + Paracetamol (= Acetaminophen) + Caffeine Tablets (250 mg + 250 mg + 50 mg) 1.......................... Acetylsalicylic acid......9 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........................670 mg Form .......................2.......... 20–25 °C) Weight ........ Kollidon 90 F [1] ....................... s..............................16 g 2...........670 mg Hardness................................................... 3........................45 N Disintegration ..................... crystalline (Merck) ........6 min Friability.........65 N Disintegration ............. Physical stability (12 months.........................................8 mm screen.... Magnesium stearate [2] ..........q............0......................50 g II................................................. Formulation I.......... Tablet properties Weight .................... crystalline (Merck) ......................... add the components III and press with high compression force.....250 g Paracetamol.........

..........................................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............................100 g Caffeine (Knoll) ................... crystalline (Merck) .................................683 mg Diameter ......... pass through a sieve and press with low compression force..................5 g 2.biplanar Hardness ...................20 g Polyethylene glycol 6000.........116 N Disintegration................................. 3.......... Tablet properties Weight .400 g Paracetamol............30 g Stearic acid [7] ........................................ Manufacturing (Direct compression) Mix all components.............2.....................9 Tablet formulations (Lab Scale) Acetylsalicylic Acid + Paracetamol (= Acetaminophen) + Caffeine Tablets (400 mg + 100 mg + 30 mg) Formulation Acetylsalicylic acid.......0........ crystalline .....................30 g Ludipress [1] .............100 g Kollidon CL [1] ...............................12 mm Form ..........................................................1 – 2 min Friability.................... powder [6].......................................

..............................................01% BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 12 Months 100 % 100 % 100 % 96 % < 0.0....15 g Kollidon CL [1] ................................... 3...biplanar Hardness..........7 % 4................................................ mix and press with medium compression force..01% ......................................605 mg Diameter ......................................25 g 2........ Chemical stability of formulation No....90 N Disintegration ... Manufacturing (Direct compression) Pass all components through a 0........ closed) 0 Months Acetylsalicylic acid Vitamin C Free acetic acid Free salicylic acid 100 % 100 % < 0............250 g Paracetamol......................8 mm sieve.2..........9 Tablet formulations (Lab Scale) Acetylsalicylic Acid + Paracetamol (= Acetaminophen) Tablets (250 mg + 250 mg) Formulation Acetylsalicylic acid.............250 g Avicel PH 101 [5] ....... crystalline (Merck) .............. crystalline (Merck) ................60 g Kollidon 30 (or Kollidon VA 64) [1] ........... Tablet properties Weight .....< 1 min Friability... 2 (20–25 °C......................................12 mm Form .....01% < 0..............01% < 0..

.....20 Magnesium stearate [2] .........biplanar Hardness ........................92 N Disintegration ...................... 1 Acetylsalicylic acid................2 g g g g g g g No..................................................................325 Ascorbic acid.........................1% 726 mg 12 mm biplanar 100 N < 1 min 1% BASF Fine Chemicals Generic Drug Formulations 1998 .............120 Avicel PH 101 [5] ................................... 2 Weight ..8 mm sieve...........790 mg Diameter ....250 Sorbitol............................. crystalline [10] ...................12 mm Form .................. mix and press with medium/high compression force................ Tablet properties No................................................... 2 325 g 250 g – 100 g 12 g 30 g 3g 2.40 Kollidon VA 64 [1] .....................................2....... Manufacturing (Direct compression) Pass all components through a 0..................................... powder (BASF).....25 Kollidon CL [1] .................................................... Formulations No......2 min Friability ....... crystalline (Merck) .......... 3...................9 Tablet formulations (Lab Scale) Acetylsalicylic Acid + Vitamin C Tablets (325 mg + 250 mg) 1. 1 No..........................

4.01% < 0.01% < 0. Chemical stability of formulation No.01% .01% BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 12 Months 100 % 100 % 100 % 96 % < 0. 2 (20–25 °C) 0 Months Acetylsalicylic acid Vitamin C Free acetic acid Free salicylic acid 100 % 100 % < 0.

..90 N Disintegration .......................4 % Dissolution...............................0.....400 Ludipress [1] ............................ crystalline (Merck) ................99 Stearic acid [7] ... Formulation Acetylsalicylic acid...........0 % 100..................................... BASF Fine Chemicals Generic Drug Formulations 1998 ..............................biplanar Hardness............. 3....................516 mg Diameter .............2............................... Manufacturing (Direct compression) Mix all components.................... Tablet properties Weight .........................................97 % 4.<1 min Friability...................12 mm Form ....... pass through a 0.....8 mm sieve and press with low compression force..... 15 min.........1 Kollidon CL [1]............0 % 98. Chemical stability Storage time RT 40 °C 0 months 6 months 12 months 100..............15 g g g g 2..............................2 %.....0 % 100..............4 % 100..........84 % 30 min ............0 % The content of free salicylic acid remained always below 0.....9 Tablet formulations (Lab Scale) Acetylsalicylic Acid Tablets (400 mg) 1......................................0 % 100......

.........707 mg Diameter .............................................7 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............................15 Kollidon CL [1] .......<1 min Friability............................................................ Formulation Acetylsalicylic acid (Merck) ............2.......................0..... Manufacturing (Direct compression) Pass all components through a 0....biplanar Hardness..............................................12 mm Form ..........3 g g g g g 2.............................200 Kollidon 30 [1] .............................500 Avicel PH 101 [5] ......... mix and press with low compression force.................................................................... 3.................9 Tablet formulations (Lab Scale) Acetylsalicylic Acid Tablets (500 mg) 1...61 N Disintegration ............... Tablet properties Weight ......8 mm sieve.................25 Magnesium stearate [2] ............................

....................0 g Sorbitol [10] ...... – The substitution of citric acid by sodium citrate impairs strongly the redispersibility..0....... Manufacturing Suspend acyclovir and Kollidon CL-M in the solution of the other components under vigorous stirring......................................... Remarks – The substitution of Kollidon 30 by Kollidon 90F gives a more compact sediment....................................................q....8 Liquid Formulations (Lab scale) Acyclovir Oral Suspension (2 % = 200 mg/10 ml) 1........0 g Citric acid ..................................5 g 2........6........3......................white Relative sediment volume after 14 days ..............96 % Redispersibility after 14 days......28..................s.. Properties of the solution Colour ..60....................easy 4....... 3.................................... BASF Fine Chemicals Generic Drug Formulations 1998 . Water......0 g Kollidon 30 [1] .......................2............... – The deletion of citric acid gives a much more compact sediment..................5 g Preservative ..............5..... Formulation Acyclovir ...................0 g Kollidon CL-M [1] .

2 g g g g g g 2.... Albendazole ...... crystalline [10]...8 mm screen.... Instant granules (200 mg albendazole sachet): Suspend 5 g of the granules (= 200 mg albendazol) in a glass of water. The obtained suspension has no bitter taste................................. Fill 50 g of the granules in a 100 ml flask (= dry syrup) or 5 g in sachets (= instant granules) 3.... pass through a 0...4 Formulation of granules.......4.22 Lutrol F 68 [1] ..3 Sorbitol............ Manufacturing Granulate mixture I with solution II...................... The suspension has no bitter taste.................... dry syrups and Iyophylisates (Lab scale) Albendazole Dry Syrup or Instant Granules (200 mg) 1...88 Ethanol 96 % ....................3 Sodium citrate.................. Formulation I..................... II................................................. Administration forms Dry syrup (200 mg albendazole /10 ml): Fill the flask containing 50 g of granules with water to the 100 ml mark..............4 Citric acid ............. dry and sieve again...... BASF Fine Chemicals Generic Drug Formulations 1998 ..............

2.9 Tablet formulations (Lab Scale)

Albendazole Tablets,
(100 mg)

1. Formulation
Albendazole ............................................100
Ludipress [1] ...........................................288
Magnesium stearate [2] ...............................4
Aerosil 200 [4] .............................................8

g
g
g
g

2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low
compression force.

3. Tablet properties
Weight .................................................400 mg
Diameter ...............................................12 mm
Form ...................................................biplanar
Hardness..................................................99 N
Disintegration ..........................................2 min
Friability ...................................................0.1%

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Alginic Acid + Aluminium Hydroxide +
Magnesium Silicate Tablets
(500 mg + 100 mg + 25 mg)
1. Formulation
Alginic acid .............................................500
Aluminium hydroxide dried gel (Giulini) ......100
Magnesium trisilicate .................................25
Sodium bicarbonate.................................170
Sorbitol, crystalline [10] ............................160
Sucrose, crystalline .................................627
Ludipress [1] ...........................................900
Kollidon VA 64 [1] ......................................70
Magnesium stearate [2]..............................50
Vanillin ........................................................5

g
g
g
g
g
g
g
g
g
g

2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with high
compression force.

3. Tablet properties
Weight ...................................................2.55 g
Diameter ...............................................20 mm
Form ...................................................biplanar
Hardness ................................................120 N
Friability...................................................1.3 %

BASF Fine Chemicals Generic Drug Formulations 1998

6.7 Formulations of semi-solid drugs (Lab scale)

Aloe Vera Gel

1. Formulation
I.

Aloe vera extract 200 fold .........................0.4 g
Propylene glycol Pharma [1] ......................5.0 g
Preservative ...............................................q.s.
Water.....................................................73.6 g
II. Cremophor RH 40 [1]................................1.1 g
Perfume .....................................................q.s.
III. Lutrol F 127 [1] .......................................20.0 g

2. Manufacturing
Prepare the solutions I and II separtely and add I onto II. Cool this
mixture to < 10 °C (or heat to 70 – 80 °C) and dissolve III. Maintain the
temperature until the air bubbles escaped.

3. Properties of the gel
Appearance
Viscosity
pH
Physical stability

clear ·
about 60 Pa · s
about 5.5
no change of appearance after 4 weeks at room
temperature

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Alpha-Bisabolol Aqueous Mouth Wash
Solution (0.2 %)

1. Formulation
I.

II.

Alpha-Bisabolol, natural (BASF) .................0.2 g
Flavour .......................................................q.s
Cremophor RH 40 [1] ...............................2.5 g
Glycerol ...................................................5.0 g
Saccharin sodium .....................................0.1 g
Preservative ...............................................q.s.
Water.....................................................92.2 g

2. Manufacturing
Heat mixture I to about 60 °C and add slowly the warm solution II (60 °C).

3. Properties of the solution
Clear, colourless liquid having a low viscosity.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Alpha-Bisabolol Buccal or Topical Solution
(0.1%)

1. Formulation
I.

II.

Alpha-Bisabolol, racemic (BASF)..............0.12 g
Cremophor RH 40 [1]..............................1.00 g
Butylhydroxytoluene ...............................0.01 g
Preservative ...............................................q.s.
Water........................................................99 g

2. Manufacturing
Heat mixture I to about 60 °C, stirr well and add slowly the warm solution II. A clear solution is obtained.

3. Chemical stability (40 °C)
No loss of alpha-Bisabolol after 3 months.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Alpha-Bisabolol Ethanolic Mouth Wash
Solution (1%)

1. Formulation
I.

II.

Alpha-Bisabolol, racemic (BASF) ...............1.0 g
Flavour...................................................10.0 g
Cremophor RH 40 [1] ...............................6.0 g
Glycerol ...................................................1.0 g
Saccharin sodium.....................................0.2 g
Ethanol, 96 % .........................................81.8 g

2. Manufacturing
Heat mixture I to about 60 °C and add slowly the warm solution II.

3. Properties of the solution
Clear, colourless liquid which can be diluted with water.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Alpha-Bisabolol Mouth Wash Solution
(0.5 %)

1. Formulation
I.

II.

(-)Alpha-Bisabolol, natural (BASF)..............0.5 g
Lutrol F 127 [1] .........................................5.0 g
Flavour ......................................................q.s.
Propylene glycol Pharma [1] ....................10.0 g
Ethanol 96 % ..........................................30.0 g
Water.....................................................54.5 g

2. Manufacturing
Prepare solution I and add slowly the water.

3. Properties of the solution
The clear colourless solution had got the pH 8.

4. Remark
The neutralisation to pH 5 – 7 would be recommended.

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Alpha-Methyldopa Tablet Cores
(250 mg), DC

1. Formulation
Alpha-Methyldopa ...................................250 g
Ludipress [1] ...........................................350 g
Stearic acid [7] ..........................................15 g

2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with low
compression force.

3. Tablet properties
Weight .................................................620 mg
Diameter ...............................................11 mm
Form ..................................................biconvex
Hardness ................................................123 N
Disintegration ..........................................6 min
Friability...................................................0.2 %
Dissolution (10 min) ...................................91%
(20 min)...................................98 %

4. Physical stability (20 months, 20–25 ºC)
Weight .................................................620 mg
Hardness ................................................115 N
Disintegration ..........................................7 min
Friability...................................................0.5 %
Dissolution (10 min) ...................................91%
(20 min) .................................100 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Alpha-Methyldopa Tablet Cores
(250 mg), WG

1. Formulations
No. 1

No. 2

Alpha-Methyldopa ........................................275 g
Lactose monohydrate [8] ................................55 g
Calcium phosphate, dibasic [9] ............................–
II. Kollidon 30 [1] ................................................15 g
Isopropanol ..................................................80 ml
III. Kollidon CL [1] .................................................8 g
Magnesium stearate [2] ....................................2 g

275 g

55 g
15 g
80 ml
8g
2g

I.

2. Manufacturing (Wet granulation)
Granulate mixture I with solution II, pass through a sieve, mix the dry
granules with III and press with medium compression force.

3. Tablet properties
No. 1

No. 2

Weight ......................................................361 mg
Diameter ....................................................11 mm
Hardness .....................................................118 N
Disintegration ...............................................5 min
Friability......................................................<0.1%
Dissolution (10 min)........................................45 %
(20 min) .......................................82 %
(30 min) .......................................90 %

362 mg
11 mm
156 N
4 min
<0.1%
55 %
90 %
98 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Alpha-Methyldopa Tablets
(500 mg), DC

1. Formulations
No. 1

No. 2

Alpha-Methyldopa .......................................500 g
(Alpha Chemicals)
Avicel PH 101 [5] ............................................54 g
Kollidon VA 64 [1] ...........................................20 g
Kollidon CL [1] ...............................................20 g
Talc [10] .........................................................90 g
Aerosil 200 [4]..................................................7 g
Magnesium stearate [2] ....................................2 g
Calcium arachinate [2] .........................................–

500 g
200
30
20
8
1

g
g
g
g
g

1g

2. Manufacturing (Direct compression)
Pass magnesium stearate trough a 0.2 mm sieve and the other components through a 0.5 mm sieve, mix and press with high compression
force (Formulation No. 1) and low compression force (Formulation No. 2).

3. Tablet properties
No. 1

No. 2

Weight
..........................................693 mg
Diameter
...........................................12 mm
Form
..........................................biplanar
Hardness
..............................................80 N
Disintegration ...........................................<1 min
Friability
.............................................0.4 %
Dissolution, 4 min ........................................86 %
16 min ......................................92 %

750 mg
12 mm
biplanar
113 N
1 – 2 min
0.8 %

BASF Fine Chemicals Generic Drug Formulations 1998

Remark In the case of formulation No. 1 it was not possible to press tablet cores of a biconvex form because some capping effect was observed.4. BASF Fine Chemicals Generic Drug Formulations 1998 .

.......................... 15 g 8g 2g – 2g I...................................................0...................................5 min Friability .........9 Tablet formulations (Lab Scale) Alpha-Methyldopa Tablets (500 mg)....................................30 g Kollidon 90 F [1] ...................................................... mix with III and press with low/medium compression force..– II....biplanar Hardness ................................................200 g Corn starch [3] ..... WG 1.................................... 2 Weight .......500 g Lactose monohydrate [8] ..................... 2 Alpha-Methyldopa .....................................98 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................................790 mg Diameter ...................................... Kollidon 30 [1]...– Isopropanol ..........................................................................8 g Calcium arachinate [2] ..........................................5 g Magnesium stearate [2] .... 3..... Formulations No...................................12 mm Form .......80 N Disintegration ......... pass through a 0......s... Manufacturing (Wet granulation) Granulate the mixture I with solution II......35 ml III....................................................................................... 2........8 mm sieve....2..... 1 No.............. Kollidon CL ..– Aerosil 200 [4]........................................5 % 696 mg 12 mm biplanar 95 N 4 min 0....................... Tablet properties No...20 g Talc [10] ....– 500 g – 200 g – 10 g q.......... 1 No............

BASF Fine Chemicals Generic Drug Formulations 1998 . Remark For the production of tables cores for coating purposes the oblong form would be better.4.

...............5 g Ludipress [1] ...........................................................3 min Friability .............................................. BASF Fine Chemicals Generic Drug Formulations 1998 ....... Tablet properties Weight ....8 mm screen and press with low compression force..... Formulation Alprazolam...........................................148 g Magnesium stearate [2] ... Manufacturing (Direct compression) Mix all components.....5 mg) 1.................. 3..1% 4......<0....... sieve through a 0....1 g 2....................158 mg Diameter .....2..........9 Tablet formulations (Lab Scale) Alprazolam Tablets (0..................................................................0.8 mm Form ................106 N Disintegration .......................................... Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation........biplanar Hardness ..............................

...540 mg Diameter ..............8 mm sieve....28 II..................biplanar Hardness .........................................5 g g g g g g g g 2.......... Kollidon CL [1] .......5 Isopropanol ....................... Aluminium acetylsalicylate ............................................ mix with III and press with medium compression force.......................................4 % BASF Fine Chemicals Generic Drug Formulations 1998 ................................1 – 2 min Friability...................about 50 III............255 Mannitol ......0............. Kollidon 90 F [1] .........................................................110 N Disintegration........23 Magnesium stearate [2] ..............................................9 Tablet formulations (Lab Scale) Aluminium Acetylsalicylate Tablets (250 mg) 1............. 3.................................................. pass through a 0.. dry.................................. Manufacturing (Wet granulation) Granulate mixture I with solution II......................................................213 Corn starch [3] ......12 mm Form ................ Tablet properties Weight .........2.10 Lutrol E 6000 [1]......... Formulation I................

......29...... 4... Properties of the suspension – Homogeneous and without sedimentation during more than 24 h...........5...25.0 Kollidon 30 [1] ....4 Formulation of granules................... 3........0 Coconut flavour....0..... Aluminium hydroxide dry gel (Giulini) .................6 Orange flavour ...........................0 Basic Magnesium carbonate ...........10.......0............. dry syrups and Iyophylisates (Lab scale) Aluminium Hydroxide + Magnesium Carbonate Dry Syrup (12.............................................. II....................................... Formulation I...4 Banana flavour ....about 36.................5 Water....... crystalline [10] ...25........... pass through a sieve and dry. BASF Fine Chemicals Generic Drug Formulations 1998 ..4...........0........................... Preparation of the suspension for administration Shake 58 g of the granules with 100 ml of water..1 ...........5 % + 12.........0.....0 Kollidon CL-M [1]..........5 Saccharin sodium. – Redispersibility very easy...0 g g g g g g g g g g g 2......0 Sorbitol.. Manufacturing Granulate mixture I with solution II...25........................................5 %) 1................

Relative sediment volume after 24 h [%] 5. Influence of the amount of Kollidon Cl-M on the sedimentation of the obtained suspension 100 80 60 40 20 0 0 4 8 Kollidon CL-M in the administration form [%] BASF Fine Chemicals Generic Drug Formulations 1998 12 .

...8 mm screen............................................160 Magnesium oxide ..............................30 min Friability..............130 N Disintegration ................................................................. Manufacturing (Wet granulation) Granulate mixture I with the simethicone suspension II........ Properties of the tablets pressed with two different diameters 12 mm 20 mm Weight ..........................13 g g g g g g g g g g g 2................. Formulation I.7 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................... Sucrose .................................................................................1200 mg Form ....576 Aluminium hydroxide......................................2......... sieve through a 0..............................................97 Kollidon 90 F [1] .............................................9 Saccharin sodium..............................45 Aerosil 200 [4] .................biplanar Hardness......................1% 1295 mg biplanar 55 N 7 min 0...........................1 Talc [10] .. 3........ add III and press with high compression force.........300 III..... suspension 30 % ....................... dry. Simethicone.................................157 Magnesium carbonate ....22 II................. Menthol ..............0....49 Magnesium stearate [2]........9 Tablet formulations (Lab Scale) Aluminium hydroxide + Magnesium carbonate/oxide + Simethicone Tablets (150 mg + 250 mg + 90 mg) 1..........................

.... Properties of the suspension Colour: ........Homogeneous..... II... III............0 g Kollidon CL-M [1] ... Citric acid . Add emulsion I to the stirred suspension II and adjust the pH to about 9 with citric acid if needed......5..........................10.. s.........................0......8 Liquid Formulations (Lab scale) Aluminium Hydroxide + Magnesium Hydroxide + Simethicone Suspension (8 % + 8 % + 0...........0..... Mix Cremophor RH 40 with simethicone..5 g Saccharin sodium ...................8.....3..................... Simethicone 30 % ........................ magnesium hydroxide and Kollidon CL-M......................ad 100 ml III............... milky Relative sediment volume (1 day):....................................................0 g Sorbitol.....................0...7......0 g Magnesium hydroxide. Dissolve the flavours and saccharin in water and suspend aluminium hydroxide...............0 g Water ....... Manufacturing I...q........0 g Banana flavour ........................ heat to about 50 °C stirring well and add the warm water................1 g Water....................8 %) 1..White Aspect: ..2.4 g Coconut flavour...... crystalline [10] ....................7 g Cremophor RH 40 [1] .8 –10........ Aluminium hydroxide dry gel (Giulini) ..........................0 g II................... Formulation I....... 3.. to adust pH 9 2................................................99 % BASF Fine Chemicals Generic Drug Formulations 1998 .............8.................

.................................100 g II............................ Manufacturing (Wet granulation) Granulate mixture I with solution II....8 mm sieve............................................................1013 mg Diameter ......2............................................................ Formulation I................200 g Lactose monohydrate [8].. Tablet properties Weight.. dry............30 g Water......... crystalline (Merck) ...................................biplanar Hardness .............60 g Aerosil 200 [4] ...260 g III.......................................................... powder [6]............................................... add III and press with high compression force (20 kN).............................. Kollidon VA 64 [1] ..................6 g 2......0. pass through a 0.........2 % BASF Fine Chemicals Generic Drug Formulations 1998 ............................................................6 g Magnesium stearate [2] ........................ Aluminium hydroxide (Rorer)..100 g Polyethylene glycol 6000..16 mm Form .9 Tablet formulations (Lab Scale) Aluminium Hydroxide + Magnesium Hydroxide Chewable Tablets (200 mg + 200 mg) 1................27 min Friability....................................... 3.....................200 g Magnesium hydroxide (Rorer) ... Sucrose...131 N Disintegration ..12 g Talc [10] ........315 g Sorbitol..... crystalline................

........ 3............0 Silicon oil DC 200 (Serva) .......8 Liquid Formulations (Lab scale) Aluminium Hydroxide + Magnesium Hydroxide Suspension (4 % + 4 %) 1.............................5..4.0......... Properties of the suspension There was only a slow sedimentation during storage and the redispersibility after weeks was excellent.......76.........0 Magnesium hydroxide..........................0 Water.............. add the water and suspend the solid substances. BASF Fine Chemicals Generic Drug Formulations 1998 ..........5...........0 Cremophor RH 40 [1] .......... Manufacturing Mix Cremophor RH 40 well with the silicon oil... Formulation Aluminium hydroxide .............4....................1 Kollidon CL-M [1].......10.9 g g g g g g 2.......................

............ Tablet properties Weight ...............6.........................................640 mg Diameter ..............83 N 4...........................................0 Ludipress [1] ... BASF Fine Chemicals Generic Drug Formulations 1998 ..................................5 g g g g g g g 2..120....................biplanar Hardness..........0 Aerosil 200 [4] ....6.........................0 Magnesium stearate [2].......................0 Menthol ...... Remarks Due to the poor flowability of the powder the tabletting machine should be equipped with a special technical device providing a continuous and homogenous filling of the dies..................................12..........................16 mm Form ..........8 mm sieve and press with a compression force of 20 kN.1...................250........ Manufacturing (Direct compression) Mix all components.. pass through a 0. Formulation Aluminium hydroxide dried gel (Giulini) ......0 Magnesium trisilicate .232..........9 Tablet formulations (Lab Scale) Aluminium Hydroxide + Magnesium Silicate Chewable Tablets (120 mg + 250 mg) 1......................................0 Cyclamate sodium ..............2.. 3.................

5 g 2......82 % BASF Fine Chemicals Generic Drug Formulations 1998 ........ 3.......0 g Ludipress [1] ......5 g Magnesium stearate [2].................................250 mg Diameter .. Formulation Ambroxol hydrochloride ............ 30 min ...................8 mm sieve and press with low compression force.....0.................................2 % Dissolution......................... pass through a 0...............................................................8 mm Form .. Manufacturing (Direct compression) Mix all components.....................biplanar Hardness ....................30..............217................................................................. Tablet properties Weight ................................2....................2......7 min Friability.....9 Tablet formulations (Lab Scale) Ambroxol Tablets (30 mg) 1.........................115 N Disintegration .....

..... Manufacturing (Wet granulation) Granulate mixture I with solution II........ 2 Weight ..30 g III.. 2..........................80 N Disintegration .............................................................................................4 % 180 mg 8 mm biplanar 72 N 6 – 7 min 0...179 mg Diameter .......– Kollidon VA 64 [1]..................3 g II....................80 g Corn starch [3] ................ powder [6] ...... Tablet properties No. 3........................ 1 No............ pass through a 0.................8 mm sieve....3 g Water .......... Formulations No...............................................2.....................................8 mm Form ......9 Tablet formulations (Lab Scale) Aminophylline Tablets (90 mg) 1........................................................... hydrous powder (Knoll) ............................biplanar Hardness ..............0.....4 g Polyethylene glycol 6000.... 1 No..... 2 Aminophylline...... Magnesium stearate [2] ....................................... Kollidon VA 64 [1].4 % BASF Fine Chemicals Generic Drug Formulations 1998 ..................90 g Potato starch [3] ........ dry.............................................................5 mm sieve and press to tablets with medium compression force........ pass through a 0...3 – 4 min Friability .................................... mix with III...........1 g Talc [10] ........– 90 g – 74 g 3g 3g 27 g – – 10 g I................................

...................0....12 g 2.........................................................................biplanar Hardness .................9 Tablet formulations (Lab Scale) Aminophylline Tablets (100 mg)...........2 g Aerosil 200 [4] .............................. Manufacturing (Direct compression) Mix all components..12 mm Form ...........................6 g Magnesium stearate [2] ...124 N Disintegration.....2...............................200 g Kollidon VA 64 [1] ...................................................... Formulation Aminophylline powder (Knoll) ...... sieve and press on a rotary press to tablets with low compression force. 3..1 – 2 min Friability................. I 1.. Remarks Due to the reduced flowability the tabletting machine should be equipped with a special technical device providing a continuous and homogenous filling of the molds........................100 g Avicel PH 200 [5] ...............................................318 mg Diameter .............................. BASF Fine Chemicals Generic Drug Formulations 1998 ..................................... Tablet properties Weight ..........2 % 4..............

........254 mg Diameter ............................... II 1.......................2 Magnesium stearate [2] ..........97 N Disintegration...... Formulation Aminophylline (Knoll) ............................................ Manufacturing (Direct compression) Mix all components.10 min Friability.....150 Aerosil 200 [4] ............................2.2 % Dissolution 10 min:.....biplanar Hardness................................................................0................................ pass through sieve and press with low compression force................................ BASF Fine Chemicals Generic Drug Formulations 1998 ................2 g g g g 2.............................8 mm Form ................................................. 3...............................................100 % 4...... Colour stability After 2 weeks at room temperature no change of the colour of the tablets was observed but the long term compatibility between aminophylline and lactose should be controlled........... Tablet properties Weight ..........................................87 % 15 min: .......9 Tablet formulations (Lab Scale) Aminophylline Tablets (100 mg).............100 Ludipress [1] .............

...........................................2.............................9 Tablet formulations (Lab Scale) Amitryptylline Tablets (10 mg and 25 mg) 1......8 mm sieve...............3 % 157 mg 8 mm biplanar 92 N 3 min 0....................................0.8 mm Form ............139 mg Magnesium stearate [2] . 2 Weight ............................................................... 2: 25 mg Amitryptylline...........................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ......................................................................biplanar Hardness ... 1: 10 mg No......... Formulations No.... 1 No.........152 mg Diameter ..70 N Disintegration. Manufacturing (Direct compression) Pass all components through a 0.........1 g 25 mg 124 mg 1 mg 2.............10 mg Ludipress [1] . Tablet properties No............. 3....................................................................1 – 2 min Friability ......... mix intensively and press with low compaction force (8 kN)..............

...............................0.. Manufacturing Mix all components and fill in a flask....................5 Lemon flavour .......9.......4 Formulation of granules..0 Citric acid.. BASF Fine Chemicals Generic Drug Formulations 1998 ...... 4...... No sedimentation could be observed during more than 24 hours.2........0 Orange flavour .. crystalline .............. Properties of the suspension The pH of the suspension is about 4.5..1.......40..5.................. The redispersibility is very easy after 2 weeks...0 Sorbitol crystalline [10] ........0 Kollidon CL-M [1] .............. dry syrups and Iyophylisates (Lab scale) Amoxicillin Dry Syrup (5 % = 500 mg/10 ml) 1.................................0 Sodium citrate............... Preparation of the suspension for administration To 66 g of the powder add water to fill to a total volume of 100 ml shaking very well...............6...... 3...........4 g g g g g g g g g 2...............................1 Sodium gluconate ..................... Formulation Amoxicillin trihydrate...............................5......4......0.....5 Saccharin sodium........

Relative sediment volume after 24 h [%] 5. Influence of the amount of Kollidon CL-M on the sedimentation of the obtained suspension 100 90 80 70 60 50 0 0 4 6 2 Kollidon CL-M in the administration form [%] BASF Fine Chemicals Generic Drug Formulations 1998 8 .

.. the dry content of an ampoule is mixed with 1.495 + 0...496..........................012.........9 ml of water to give a clear injection solution.....7... Formulation Amoxicillin sodium .. BASF Fine Chemicals Generic Drug Formulations 1998 . 3.6......012... 1979.. Patent 0.. Administration Prior to administration....add 100..50 g Water for injections . fill 500-mg-portions of the dry lyophilisate into ampoules. dry syrups and Iyophylisates (Lab scale) Amoxicillin Lyophylisate for Injection (250 mg) (according to Eur............... Beecham) 1...... Manufacturing Dissolve the active ingredient in the well stirred solution of Kollidon 12 PF and after freeze-drying.25 g Kollidon 12 PF [1] .......4.4 Formulation of granules.00 ml 2......

........... Kollidon 30 [1] .............9 Tablet formulations (Lab Scale) Amoxicillin Tablets (125 mg) 1...125 Corn starch [3] ...............................biplanar Hardness............................. dry.148 II................................ Kollidon CL [1].....................................................................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ........... Amoxicillin ........................................ Formulation I................9 Water ............................................ sieve and mix with III. 3.....................................0..............................297 mg Diameter .....................15 Magnesium stearate [2] ........ Manufacturing (Wet granulation) Granulate mixture I with solution II............... Tablet properties Weight ................ Press with low compression force........................................12 mm Form .about 60 III....3 g g g g g g 2.............4 min Friability...............................................62 N Disintegration .........2.............

.............. 3.......5 % + 4.................. Remark The castor oil should not be heated to more than 50 °C because at higher temperature a strong thickening effect was observed.... Ampicillin sodium ..91.................q.......5 g Cloxacillin sodium.........1....5 g 2.........0 %) 1............8 Liquid Formulations (Lab scale) Ampicillin + Cloxacillin Oily Suspension (1........... BASF Fine Chemicals Generic Drug Formulations 1998 ...... Properties of the suspension A homogeneous suspension was obtained.....................................0 g II........... s.. Add the components I and stir during cooling to room temperature. Lutrol F 68 [1]......... Antioxidant....0 g III............. Manufacturing Heat the mixture III to 50 °C and dissolve II..... Formulation I.... Castor oil .. 4.3........5..4..............

........0....5................. Formulation Ampicillin trihydrate ............................ The redispersibility is very easy after 2 weeks..0 Sodium citrate...........0 Sorbitol crystalline [10] ............................... 3................ Manufacturing Mix all components and fill in a flask....5 Saccharin sodium...... Properties of the suspension The pH of the suspension is about 4.........6...5..4 g g g g g g g g g 2..0 Citric acid.... No sedimentation could be observed during more than 24 hours............ Preparation of the suspension for administration To 66 g of the powder add water to fill to a total volume of 100 ml shaking very well.2...........0 Orange flavour ........................... crystalline ..........5...........4 Formulation of granules............................4..1 Sodium gluconate ............. dry syrups and Iyophylisates (Lab scale) Ampicillin Dry Syrup (5 % = 500 mg/10 ml) 1..40........................ 4.........9....5 Lemon flavour ......1.............. BASF Fine Chemicals Generic Drug Formulations 1998 .............0 Kollidon CL-M [1] .......0...........

4. dry syrups and Iyophylisates (Lab scale) Viscosity [mPa·s] 5.4 Formulation of granules. Influence of the amount of Kollidon CL-M on the viscosity of the obtained suspension 80 60 40 20 0 0 2 4 6 Kollidon CL-M in the suspension [g/100 ml] BASF Fine Chemicals Generic Drug Formulations 1998 8 .

...........................12 mm Form ...........................................9 Tablet formulations (Lab Scale) Ampicillin Tablets (250 mg) 1............ Formulation Ampicillin trihydrate ................4 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................250 g Magnesium stearate [2].....84 N Disintegration ... Tablet properties Weight ........4 min Friability..............................10 g 2... pass through a sieve and press with low compression force...............................................biplanar Hardness.................0.............................500 mg Diameter ................................................... 3.................... Manufacturing (Direct compression) Mix all components..........................................................2..........250 g Ludipress [1] ....

................. 2 Weight .... Kollidon VA 64 [1] ......................170 N Disintegration ................4 % 822 mg 16 mm 154 N 11 min 0..2.... Formulations No.........10 g Aerosil 200 [4] ......................................................0.........– II..................... 2 Ampicillin trihydrate ...... Tablet properties No............. 12 g 10 g 8g I.........2 % BASF Fine Chemicals Generic Drug Formulations 1998 .........................................12 g Magnesium stearate [2]......................................... s......................9 Tablet formulations (Lab Scale) Ampicillin Tablets (500 mg) 1. III........ pass through a 0.......8 mm sieve....16 mm Hardness ................798 mg Diameter .................................................................................... 1 No........................... mix with III and press with high/medium compression force. crystalline [10] ......25 g Isopropanol or water ....... 3...........................s....8 g 500 g – 242 g 25 g q............................ Kollidon CL [1] ......... dry.500 g Corn starch [3] ........ 2...242 g Sorbitol.......................................... Manufacturing (Wet granulation) Granulate mixture I with solution II.......5 min Friability ..q............. 1 No........................

BASF Fine Chemicals Generic Drug Formulations 1998 . Water.....1...........................................63..... Formulation I....... heat to about 65 °C.................................. Manufacturing Mix the anise oil with Cremophor RH 40................. stir strongly and add slowly the hot solution II.........s....0 g Cremophor RH 40 [1] .........q....8 Liquid Formulations (Lab scale) Anise Oil Solution (1%) 1.1.............................7 g Ethanol ........... II........................0 g Preservatives....... Properties Clear or slightly opalescent....... colourless liquid...5.34............ Anise oil ........3 g 2....... 3.

.200 Sorbitol............... 3...................................... Formulation Asparagus extract........ powder ......................biplanar Hardness...........200 Kollidon VA 64 [1] ...................................10 Magnesium stearate [2] .... mix and press with low compression force.............20 Kollidon CL [1].........2.........................4 g g g g g g 2..........200 Parsley extract..........................0 % BASF Fine Chemicals Generic Drug Formulations 1998 .......636 mg Diameter .. powder ........................................................................9 min Friability ............... crystalline [10] ....................12 mm Form .....9 Tablet formulations (Lab Scale) Asparagus Extract + Parsley Extract Tablets (200 mg + 200 mg) 1................49 N Disintegration .........................................................8 mm sieve.. Tablet properties Weight .............................................. Manufacturing (Direct compression) Pass all components through a 0.................................

........25 N Disintegration .. powder ...................1 g 2...............9 Tablet formulations (Lab Scale) Aspartame Effervescent Tablets (20 mg) 1........................14.1.66 mg Diameter ....10....... Tablet properties Weight ....................2.......... Formulation Aspartame ................................<1 min Friability......................................20..3 g Sodium bicarbonate.........4 g Tartaric acid......6 mm Form ............ 3.. powder [6].....................biplanar Hardness.... pass through a 0...0 g Sorbitol...........7 g Polyethylene glycol 6000................5 mm sieve and press to tablets...18...........................................1.............. crystalline [10] .......0.................................................. Manufacturing (Direct compression) Mix .................................7 g Kollidon 25 [1] ..............................................................7 % BASF Fine Chemicals Generic Drug Formulations 1998 ................

..1% BASF Fine Chemicals Generic Drug Formulations 1998 ......................27 Ludipress [1] ..........8 mm sieve and press to tablets with low compression force.....................................12 Magnesium stearate [2] ............. Manufacturing (Direct compression) Mix all components....................1 Lutrol F 68 [1] ...........................................<1 min Friability ............................3 g g g g g 2.............biplanar Hardness.......... Formulation Aspartame ..............2......................................0.................................65 N Disintegration ............................................... Tablet properties Weight ....................................120 mg Diameter ............................................76 Kollidon CL [1].............. DC 1...................... 3...8 mm Form ...........................9 Tablet formulations (Lab Scale) Aspartame Tablets (25 mg)........................... pass through a 0.........

........................3 g Polyethylene glycol 6000......... WG 1......................................... Tablet properties Weight .......60 mg Diameter ..................................................................2.......3 g II..... pass through a 0.......60 N Disintegration ................< 0..... Aspartame .........5 mm Form ........ Manufacturing (Wet granulation) Granulate the mixture I with II....25 g Dibasic calcium phosphate [9]...... 3.............................................. Kollidon CL [1] .........................10 g III..........1% BASF Fine Chemicals Generic Drug Formulations 1998 .............3 g 2................................................... powder [6].................................... Formulation I............ mix with III and press to tablets............biplanar Hardness.........................9 Tablet formulations (Lab Scale) Aspartame Tablets (25 mg). Water.........................................8 mm sieve...................1 min Friability ....25 g Kollidon VA 64 [1] .................

....................................2..........287....85 N Disintegration..................0 Magnesium stearate [2].......... Manufacturing (Direct compression) Mix all components.........8 mm sieve and press to tablets with low compression force.........0................0 Kollidon CL [1]......................................2 Aerosil 200 [4] ...............1% BASF Fine Chemicals Generic Drug Formulations 1998 .................52.biplanar Hardness... Formulation Atenolol (Stober)...........2 – 3 min Friability ..............................................9 g g g g g 2...................0 Ludipress [1].....................<0................ pass through a 0.....436 mg Diameter .... Tablet properties Weight ...................2.................................93.......................................9 Tablet formulations (Lab Scale) Atenolol Tablets (90 mg) 1.................... 3.12 mm Form ...................................................................

..5.......2..0 Sucrose .......9.............. Properties of the the suspension White suspension showing no sedimentation during 24 hours and good redispersibility....3 g g g g g g g g g 2....... 4. Manufacturing The mixture I is granulated with the solution II...................0 mm sieve and dried at room temperature.. dry syrups and Iyophylisates (Lab scale) Azithromycin Dry Syrup (5 % = 500 mg/10 ml) 1.................................0..................... 3...........................0....0 Ethanol . crystalline........................... Formulation I................................... The bitter taste Azithromycin is almost completely masked..................... Azithromycin dihydrate ..............5 Cremophor RH 40 [1] ...0. Fill 83 g of the granules in a 100 ml flask....60.....0 Menthol............0 Sodium cyclamate ..... The obtained granules are passed through a 1.... BASF Fine Chemicals Generic Drug Formulations 1998 ..........0 Citric acid .....9.................................................. II....5 Kollidon CL-M [1] ...0 Sodium citrate.........5.. Administration Shake 83 g of the granules with drinking water and fill the flask until the 100 ml mark....4.......4 Formulation of granules.........

.........8 Liquid Formulations (Lab scale) Azithromycin Suspension (5 % = 500 mg/10 ml) 1......0 g Sucrose .....................2 g Water ........................0 g Sodium citrate......2................ Azithromycin dihydrate .....5......................ad 100 ml 2......................... The bitter taste of Azithromycin is almost completely masked.......0 g Citric acid ......0 g Kollidon CL-M [1] ..............9.. BASF Fine Chemicals Generic Drug Formulations 1998 ................5 g Chocolate flavour .. Properties of the suspensions Light-brown suspension showing no sedimentation during 24 hours and good redispersibility..0 g III......5...10.................................................. Formulations I.. Water....................... 3.........5........0.......................0.............................0 g II........... Cremophor RH 40 [1] ........... Manufacturing Add the mixture I to the solution II and fill with water to a total volume of 100 ml shaking very well................................60..

........ Formulation Azulene.............1..................0 g Cremophor RH 40 [1] ................ BASF Fine Chemicals Generic Drug Formulations 1998 ............5.....ad 100 ml 2....................... Add slowly the water (60 °C) and cool to room temperature 3....... Properties A clear solution was obtained..........0 g Water....3....... Manufacturing Mix azulene and Cremophor RH 40 and heat to about 60 °C............8 Liquid Formulations (Lab scale) Azulene solution (1%) 1.....

..... 3..........100.....8 Liquid Formulations (Lab scale) Barium Sulfate Oral Suspension (23 %) 1. BASF Fine Chemicals Generic Drug Formulations 1998 ....................... Manufacturing Dissolve the preservatives and the carboxy methylcellulose sodium in the hot water and add Kollidon 90 F and sodium bisulfite.....................................< 0. Properties of the suspension White homogeneous suspension having a viscosity of about 160 mPa · s.............................5............ Formulation Barium sulfate ...... In the obtained clear solution suspend barium sulfate.....320.........0 g 2....5..4 g Sodium bisulfite ....................0.....5 g Preservatives..................... s.....0 g Carboxymethylcellulose sodium .........0 g Kollidon 90 F [1] ........... Water ..q...................

.......0 Cremophor A 6 [1] ............. Physical stability No change of appearance were observed during 6 weeks at 45 °C.. Heat III until the active ingredient is dissolved.........0.....12....0 g g g g g g g g 2........7.....7 Formulations of semi-solid drugs (Lab scale) Basic Cream for Different Active Ingredients 1.......... Properties White cream.... mix with I/II and continue to stir during cooling to room temperature.............7 III..2-propylene glycol.................. BASF Fine Chemicals Generic Drug Formulations 1998 .........6......1. 4....................8............. This basic cream was tested with different active ingredients soluble in 1............ Propylene glycol [1] ...........5 Liquid paraffin ..2 II.......1.....0.......5 Cremophor A 25 [1] ....1 – 2............ Cetylstearyl alcohol.. Formulation I.................................................0 Active ingredient ..67.. 3.... Add the water II to the obtained solution I with rigorous stirring........ Water ............... Manufacturing Heat the mixture I and the water II separately to about 80 °C......................0 Parabene(s)...........8 – 69..

. 1 No................................................ Manufacturing (Direct compression) Mix all components for 10 minutes in a turbula mixer and press with low compression force........................ 1 No.............0 14................ 3...................................................................0 g (= trihexylphenidyl hydrochloride) Ludipress [1].....0 g Corn starch [3] ............................120 N Disintegration .....0 g 100.– Magnesium stearate [2] ........................2............5.4 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........................................................5 mm Form .. Formulations No.......... Tablet properties No......................................– 5.6 g Aerosil 200 [4].......0...................................9 Tablet formulations (Lab Scale) Benzhexol Tablets (5 mg) 1....< 0................................ 2 Weight ........................................................ 2 Benzhexol chloride ..................7 min Friability .....5 g g g g 2..06 % 121 mg 5 mm biplanar 113 N 3 min 0.........5 0..5 1..biplanar Hardness.120 mg Diameter ....................114..........

.........0 g III........ natural (BASF) ................... Carbopol® 940 (Goodrich) ......0 g Kollidon 30 [1] ........... Benzoyl peroxide ........5...2 g Propylene glycol Pharma [1] ..........0 g Water............................. Formulation I...............................................7 Formulations of semi-solid drugs (Lab scale) Benzoyl Peroxide + Alpha-Bisabolol Gel (5..3.0 g Cremophor RH 40 [1] ..0 g Water.............................6..0..... 3...... BASF Fine Chemicals Generic Drug Formulations 1998 ..............8 g II. Add this suspension to the well stirred solution I...............................0 % + 0..............1.... Manufacturing Prepare suspension II and let swell during one hour....40.0 g Triethanolamine ................................. Add III......... Alpha-Bisabolol.....1.....2 %) 1..............3...6....0 g 2.40.. Properties of the gel Colourless transparent gel..

.22 Ethanol 96 % ..41 Water . Manufacturing Heat the mixture of benzyl benzoate and Cremophor RH 40 to about 60 °C..................27 g g g g 2......... BASF Fine Chemicals Generic Drug Formulations 1998 ..........8 Liquid Formulations (Lab scale) Benzyl Benzoate Solution (10 %) 1..5...10 Cremophor RH 40 [1] .............................................. Formulation I...................... Finally add the ethanol... 3................................................ Properties of the solution Clear.. colourless liquid. Benzyl benzoate .......... stir strongly and add slowly the water.....

.......ad 100 ml 2.............................. BASF Fine Chemicals Generic Drug Formulations 1998 ...0 g Kollidon 12 PF [1] ......0......s.......... add the components I to the well stirred solution II and pass through a colloid mill.......5 g Sodium citrate..5 g Carboxymethyl cellulose sodium .0..6 g Parabene .000 units + 200 mg/ml) 1..... 3........ Procain benzylpenicilline ...2 to 0.5 % of cysteine could be added as antioxidant............8 Liquid Formulations (Lab scale) Benzylpenicilline + Dihydrostreptomycin Injectable Suspension (200.......... Remark To prevent of discolouration of Kollidon in the solution during storage 0. Formulation I..........5.... Properties A white homogeneous suspension was obtained..........20... II................q.... 4............ Manufacturing Prepare solution II..20..............................0 g Dihydrostreptomycin sulfate ....0............ Water for injectables ................

......6 mm Form ......biplanar Hardness.1 min Friability .......................... Manufacturing (Direct compression) Mix all components..40 N Disintegration ........54............................................1......7 Lactose monohydrate [8].........................................................................2.2 g g g g 2................5............................... 3................................1 Ludipress [1] ........................................ Formulation Berberine sulfate .......................................54................. pass through a 0...........9 Tablet formulations (Lab Scale) Berberine Tablets (5 mg) 1....0.......1% BASF Fine Chemicals Generic Drug Formulations 1998 ...................................1 Magnesium stearate [2].115 mg Diameter ... Tablet properties Weight........................8 mm sieve and press with low compression force.......

........9 Tablet formulations (Lab Scale) Beta Carotene + Vitamin C + Vitamin E Chewable Tablets (10 mg + 500 mg + 250 mg) 1.......................................600 mg Diameter ..... crystalline (BASF) ................4 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................2................. Formulation Beta Carotene dry powder 10 % .............280 g Vitamin E acetate dry powder SD 50 ........................................350 g Polyethylene glycol 6000......250 g Sodium ascorbate.........................................2...............................0.......... crystalline [10] .................................................................... Manufacturing (Direct compression) Mix all components................. pass through a sieve and press with high compression force..............600 g Ludipress [1] ..... Tablet properties Weight ..................122 N Disintegration (water) ......biplanar Hardness ...50 g 2....20 mm Form .....15 – 20 min Friability.......................500 g (BASF) Sorbitol..... 3............500 g Fructose . crystalline..........100 g Ascorbic acid............................ powder [6].

.2 % 4.................... powder (BASF) ................................3 % 502 mg 12 mm biplanar 59 N 7 min 0............ 1 (40 °C........8 mm sieve.................. mix and press with medium or high compression force...................... Manufacturing (Direct compression) Pass all components through o 0.....................................................................................12 mm Form .............................................– Kollidon CL [1] ....................369 g Sorbitol.0........ 3............ 1 No...........2... Formulation No..............................................9 Tablet formulations (Lab Scale) Beta Carotene + Vitamin C + Vitamin E Tablets (6 mg + 100 mg + 30 mg) 1. closed) Beta carotene/tablet 0 weeks 15 weeks 80 mg 78 mg BASF Fine Chemicals Generic Drug Formulations 1998 ...... 1 No...biplanar Hardness ......... 2 Weight .... crystalline (Merck) .60 N Disintegration (water) .......................................... Tablet properties No.................599 mg Diameter ..........65 g Ascorbic acid.................. Chemical stability of beta carotene in Formulation No............................6 g 65 g 100 g 60 g – 233 g 30 g 8g 4g 2........– Magnesium stearate [2] .....................................60 g Ludipress [1] ....7 min Friability ..........100 g Vitamin E acetate dry powder 50 % .............................– Kollidon VA 64 [1]......................... 2 Betavit ® dry powder 10 % (BASF) .......

BASF Fine Chemicals Generic Drug Formulations 1998 . The tablets of Formulation No. Remarks A colourant pigment should be added to obtain a homogeneous appearance of the tablets.5. 1 could be commercialized in Europe as dietary food because all components are allowed for this application.

......... mix and press with low compression force......1% 4.....................2.8 min Friability ....9 Tablet formulations (Lab Scale) Beta Carotene + Vitamin C + Vitamin E Tablets (7 mg + 60 mg + 25 mg) 1........................5 g 2.......... Formulation Betavit® dry powder 10 % (BASF) ...................... powder (BASF)................ Tablet properties Weight .........................................................................240 g Kollidon CL [1] .......497 mg Diameter .................... Manufacturing (Direct compression) Pass all components through a 0.............50 g Sorbitol...........................biplanar Hardness........8 mm sieve........... crystalline [10] ... BASF Fine Chemicals Generic Drug Formulations 1998 ......... These tablets could be commercialized in Europe as dietary food because all components are allowed for this application................55 N Disintegration .......< 0...... Remarks A colourant pigment should be added to obtain a homogeneous appearance of the tablets.30 g Magnesium stearate [2] ...... 3.......................................75 g Ascorbic acid.........60 g Vitamin E acetate dry powder 50 % .12 mm Form ..............................................................................

............................9 Tablet formulations (Lab Scale) Beta Carotene + Vitamin C + Vitamin E Tablets (12 mg + 250 mg + 125 mg) 1....10 g 2......141 g Vitamin E acetate dry powder SD 50 ......................................50 N Disintegration ..........119 g Polyethyleneglycol 6000............................................ crystalline (BASF) ......... pass through a sieve and press with medium compression force... 3........not tested Friability ...............250 g (BASF) Ludipress [1] or Sorbitol........... Formulation Beta Carotene dry powder 10 % ...790 mg Diameter ..............< 0....................125 g Sodium ascorbate. crystalline [10] ...12 mm Form ....................... Manufacturing (Direct compression) Mix all components.............................5 g Orange flavour (FDO) ........2...biplanar Hardness.......... crystalline (BASF)..............................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...... Tablet properties Weight ....................125 g Ascorbic acid...........15 g Sodium cyclamate ...................... powder [10] .........................

.........................................12 mm Form .....................8 mm sieve................................................... powder [6]............................................602 mg Diameter ................2 % BASF Fine Chemicals Generic Drug Formulations 1998 .........................4 % 605 mg 12 mm biplanar brown 108 N 50 sec 0...20 g Polyethylene glycol 6000..................15 g Orange flavour ...............................................70 g Ludipress [1]...........0...biplanar Colour.............................30 g 2.................... Tablet properties Compression force 18 kN 26 kN Weight ... Manufacturing (Direct compression) Pass all components through o 0.....81 N Disintegration (water) .................200 g Sodium bicarbonate.....................120 g Sodium carbonate .......................9 Tablet formulations (Lab Scale) Beta Carotene Effervescent Tablets (7 mg) 1..........................2.........................................................................................12 g Sodium cyclamate ....................... 3...113 g Citric acid...brown Hardness ............ Formulation Lucarotin ® dry powder 10 % CWD (BASF) ............20 g Aspartame .............. anhydrous .........................................................45 sec Friability .. mix and press with medium or high compression force at maximum 30 % of relative atmospheric humidity...................

........2......................................5 g g g g g – 2......................................– Kollidon CL [1] ..240.........................– 5 % Kollidon 30 Avicel PH 101 [5]........................................................... 2 Beta carotene dry powder 10 % ........0 g 150..........2.........1% 502 mg 12 mm biplanar 57 N 1 min 0% BASF Fine Chemicals Generic Drug Formulations 1998 ..................0 g Dicalcium phosphate [9]...biplanar Hardness ..59 N Disintegration ........ 2 Weight .............................. pass through a 0..........12 mm Form ..............................................0 g Ludipress [1] ..................8 mm sieve and press with a medium compression force........12 min Friability........9 Tablet formulations (Lab Scale) Beta Carotene Tablets (15 mg) 1......0 g 100.......– Talc [10] ......0 g Aerosil 200 [4]....................0 5...................................................0 2.................... granulated with .... 1 No.................................0 g – 175...0........6.............– Calcium arachinate [2] ..............................0 2..............5 20....................... Formulation No.160...... 3.................. Manufacturing (Direct compression) Mix all components............................ Tablet properties No............................ 1 No........................– Magnesium stearate [2] .....400 mg Diameter ......

2: Loss of beta carotene BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 12 Months 3% 60 N 9 min 0. 1: Loss of beta carotene Hardness Disintegration Friability Formulation No.2.16 % 6 Months 12 Months <8% 9% .9 Tablet formulations (Lab Scale) 4.15 % 4% 59 N 7 min 0. Chemical and physical stability (20–25 °C) Formulation No.

......................9 Tablet formulations (Lab Scale) Beta Carotene Tablets (20 mg) 1.........................................................................2 g g g g 2................110 % (= 22 6 Months: ..................................250 Kollidon CL [1] ............................................................. 95 % (= 19 12 Months: .............20 Aerosil 200 [4] ................. 95 % (= 19 mg) mg) mg) mg) 5.....biplanar Hardness.............................. protected from light) 0 Months: .....90 N Disintegration ............................................. 95 % (= 19 9 Months: ................... Manufacturing (Direct compression) Mix all components and press with a low compression force..............................12 mm Form .........0.. Formulation Beta carotene dry powder 10 % ...................................................518 mg Diameter ................ BASF Fine Chemicals Generic Drug Formulations 1998 ..220 Avicel PH 101 [5] ..................5 % 4..........................2... 3.......... Tablet properties Weight ...... Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application..................... Chemical stability (20–25 °C...< 1 min Friability.....................

..20..............00 Water ....00 g g g g g g 2.......15............7 Formulations of semi-solid drugs (Lab scale) Betamethasone + Neomycin Gel-Cream (0......... 3................13 Neomycin sulfate .ad 100..... Mix both solutions......... Properties of the gel-cream A milky white soft gel-cream is obtained.. BASF Fine Chemicals Generic Drug Formulations 1998 ...................0..........................1% + 0.......6 %) 1.........65 Lutrol E 400 [1] .......... Maintain cool until the air bubbles disappeared.....6..00 Miglyol ® 812 (Dynamit-Nobel) ....... Manufacturing Dissolve betamethasone valerate in the mixture of Lutrol E 400 and Miglyol 812.0...............00 Lutrol F 127 [1] .....10.................. Formulation Betamethasone valerate ... Dissolve Lutrol F 127 and neomycin sulfate in water at 5 –10°C......

....0.........0 Betamethasone ........ 3......... Add the water II to the obtained solution I with rigorous stirring................12............... Cetylstearyl alcohol..... Water..................1.......1... Remark This formulation could be used for other active ingredients too.................0 Parabene(s)................7 Formulations of semi-solid drugs (Lab scale) Betamethasone Cream (0.............0 Cremophor A 6 [1] .. Properties White cream...8..5 Liquid paraffin ............ BASF Fine Chemicals Generic Drug Formulations 1998 ............69......6......................................2 II..1%) 1...................... Formulation I...1 g g g g g g g g 2.0... 4..............7........... mix with I/II and continue to stir during cooling to room temperature........7 III...5 Cremophor A 25 [1] ............. 5........... Manufacturing Heat the mixture I and the water II separately to about 80 °C...... Heat III until the active ingredient is dissolved....................... Propylene glycol [1] ..... Physical stability No change of appearance or crystallization were observed during 6 weeks at 45 °C....

................0 Lutrol F 127 [1] .... 4.......10......0... Mix both solutions...........22.0 g g g g g 2..... Maintain the temperature until the air bubbles disappeared.........6.....47. Betamethasone valerate ....20.........1 Ethanol 96 % ...... 3.0 Water ..... Remark Perhaps a certain amount of propylene glycol could be substituted by water.........1%) 1.................... II....... Properties of the gel The obtained gel is clear and colourless.................................. Formulation I.. Manufacturing Prepare the solution I at room temperature and solution II at about 6 °C (or at > 70 °C).......... BASF Fine Chemicals Generic Drug Formulations 1998 ..........7 Formulations of semi-solid drugs (Lab scale) Betamethasone Gel (0..............0 Propylene glycol Pharma [1] .

.....5 Liquid paraffin ...........7.1....... Manufacturing Heat the mixture I and the water II separately to about 80 °C.............0 Cremophor A 6 [1] ............8..............8 III............. Add the water II to the obtained solution I with rigorous stirring..2 II..... Physical stability No change or appearance or crystallization were observed during 6 weeks at 45 °C...........7 Formulations of semi-solid drugs (Lab scale) Bifonazole Cream (1%) 1.0..................... Propylene glycol [1] ..... mix with I/II and continue to stir during cooling to room temperature....68.................6..................... BASF Fine Chemicals Generic Drug Formulations 1998 ...........................1........0 g g g g g g g g 2..... 4.......... 3...............12.... Heat III until the active ingredient is dissolved..........................0 Bifonazole .............................1...... 5.......... Properties White cream........ Formulation I......5 Cremophor A 25 [1] . Cetylstearyl alcohol..0 Parabene(s).......... Remark This formulation could be used for other active ingredients too............ Water.........

..................................2....................................................5 Aerosil 200 [4] .........0......................... BASF Fine Chemicals Generic Drug Formulations 1998 ..250 Ludipress [1] .................52 N Disintegration ................. 3................. pass through a sieve and press with medium compression force.............9 Tablet formulations (Lab Scale) Bran Tablets (250 mg)........4 g g g g g 2... These tablets could be commercialized in Europe as dietary food because all components are allowed for this application...............477 mg Diameter .............12 mm Form ................ Remark If the bran is not milled.........4 Magnesium stearate [2] ...4 % 4................ Formulation Bran wheat (milled <1 mm)...................................biplanar Hardness............. Tablet properties Weight ................................ the hardness of tablet is higher but the content uniformity is less................................. DC 1........................................................ Manufacturing (Direct compression) Mix all components.....................3 min Friability...................200 Kollidon 30 [1] ............

...........................12 g Water ...70 N Disintegration ..467 mg Diameter ..................12 mm Form ................ WG 1.....................q...........2................ Polyethylene glycol 6000...biplanar Hardness...........9 Tablet formulations (Lab Scale) Bran Tablets (250 mg)...3 min Friability...................... Magnesium stearate [2] ................... Manufacturing (Wet granulation) Granulate mixture I with solution II.................200 g II.................. mix with III and press with medium compression force.................................... Tablet properties Weight . Kollidon 90 F [1] . powder [6].......................................... 3............................................................. pass through a sieve..................250 g Dibasic calcium phosphate [9]....................4 % BASF Fine Chemicals Generic Drug Formulations 1998 ..3 g III...... Bran wheat (milled <1 mm)........................0...................................s.....4 g 2.......................... Formulation I..

................. Formulations No........2 % 202 mg 8 mm biplanar 70 N 1 – 2 min 0.........................................2..8 mm sieve...............5 g Magnesium stearate [2] .......................................................... mix and press with low/ medium compression force... 1 No. 1 No.................................................................................1 g 8g – 190 g – – 1g 2.........................................................biplanar Hardness .... 2 Bromhexine ...........204 mg Diameter ................ 3......................................................................................................8 mm Form ..................................0........2 % BASF Fine Chemicals Generic Drug Formulations 1998 .................... Manufacturing (Direct compression) Pass all components through a 0...............179 g Ludipress [1] ....................................................70 N Disintegration..8 g Dicalcium phosphate [9].......... 2 Weight .....< 1 min Friability .7 g Kollidon CL [1] ....................... Tablet properties No...9 Tablet formulations (Lab Scale) Bromhexine Tablets (8 mg) 1.........– Kollidon VA 64 [1]....

............................................................................8 mm sieve and press with high compression force..biconvex Hardness...........5 g Magnesium stearate [2]...............9 Tablet formulations (Lab Scale) Bromocriptine Tablet Cores (6 mg) 1................. Tablet properties Weight ............ 3..... Manufacturing (Direct compression) Mix all components..2...............................0...................................................................4 min Friability.95...) ....2 g 2.............................................214 mg Diameter .................6.........2..... Formulation Bromocriptine mesylate ........1 g Ludipress [1] .......88 N Disintegration ........6 % BASF Fine Chemicals Generic Drug Formulations 1998 .............205.......7 % Dissolution (10 min........ pass through a 0............................9 mm Form ................................

......................................................... Formulation I.. Manufacturing (Wet granulation) Granulate mixture I with the water II...... Water......................... Kollidon CL [1] ..................................... mix the dry granules with III and press with low compression force....................... precipitated ...............................656 mg Diameter .. Calcium carbonate..............97 III................53 g g g g g 2........1% BASF Fine Chemicals Generic Drug Formulations 1998 ....biplanar Hardness ...........................65 II....................12 mm Form ..............................500 Kollidon 30 [1] .........120 N Disintegration..10 min Friability ......................................0...... pass through a sieve................................... 3..........................9 Tablet formulations (Lab Scale) Calcium Carbonate Tablets (500 mg) 1........................................32 Ludipress [1] .................2............ Tablet properties Weight ..............

............. dry..................................................... 2..480 g Kollidon 30 [1] ... Kollidon CL [1] ..... powder [6]....biplanar Hardness ........................................................2 – 3 min Friability......... Formulation I..........5 % BASF Fine Chemicals Generic Drug Formulations 1998 .12 g Isopropanol ..................................................2560 mg Diameter ...........q................................................. Tablet properties Weight ... Kollidon 30 [1] .....................0.................190 g Sodium bicarbonate.............s........ Calcium lactate .....................2..................................................................410 g Tartaric acid ......................... mix with III and press with low compression force.......20 mm Form .q.650 g Calcium gluconate .......193 N Disintegration (water)....... Manufacturing (Wet granulation) Granulate mixture I with solution II.. III...........................48 g Flavour ............. 3......... sieve.............................................................................9 Tablet formulations (Lab Scale) Calcium Effervescent Tablets (250 mg Ca) 1..................100 g Polyethylene glycol 6000...s...........................................625 g Calcium carbonate...................................48 g II........................

..................90 III..biplanar Hardness .................. mix with III and press with high compression force........................118 N Disintegration (water)....................................................................................500 mg Diameter ..... Calcium gluconate.................12 mm Form . dry.....8 mm sieve.11 Isopropanol...... Formulation I............. Manufacturing (Wet granulation) Granulate mixture I with solution II......................................2 g g g g g g 2.. 3.......117 II............1% BASF Fine Chemicals Generic Drug Formulations 1998 ............< 0......16 min Friability ........................................................................9 Tablet formulations (Lab Scale) Calcium Gluconate Tablets (350 mg) 1................2...................... pass through a 0........ powder......................... Kollidon 30 [1] .............................. Tablet properties Weight .......... Kollidon CL [1] ..25 Magnesium stearate [2] ..........................................360 Lactose monohydrate [8] .

.........297.....200..................................................................12 mm Form ................5 g Magnesium stearate [2].............2.... Manufacturing (Direct compression) Pass all components through a 0..............................biplanar Hardness ..............2..0 g Ludipress [1].........7 min Friability ................................... 2...........0.....................q......8 mm sieve.......s...9 Tablet formulations (Lab Scale) Calcium Glycerophosphate Tablets (200 mg) 1.................... Tablet properties Weight ........131 N Disintegration ...................5 g Aerosil 200 [4] ....1% BASF Fine Chemicals Generic Drug Formulations 1998 ......................... 3............................................ Formulation Calcium glycerophosphate .............................. mix and press with high compression force......................470 mg Diameter .............

.................................................0 Water..................1% BASF Fine Chemicals Generic Drug Formulations 1998 .... Tablet properties Weight ...................... Kollidon 90 F [1] ....220 N Disintegration ............... Formulation I.. Kollidon CL [1] . Press with medium to high compression force..................................................12 mm Form ...2......0 Corn starch [3] ...........2.......... Calcium glycerophosphate ..........................................5 g g g g g g 2..................117......0 III.............................7 min Friability ....................500. sieve and mix with III....9 Tablet formulations (Lab Scale) Calcium Glycerophosphate Tablets (500 mg) 1.0........... dry.............................................................biplanar Hardness...............................0 Magnesium stearate [2]...........15........5 II......60.................. 3.........15.................650 mg Diameter ....... Manufacturing (Wet granulation) Granulate mixture I with solution II.............................

.............400 g Wheaten flour....8 mm sieve.... Formulation No......................................... 2 (Wet granulation) Granulate mixture I with solution II...................... Tablet properties No....................1 g Lactose monohydrate [8] ........4 g 400 g 100 g 1g 262 g q......... 1 (Direct compression) Pass all components through a 0............................................. Formulation No.................................................272 g Flavours.................... Kollidon 30 F [1] ........– Kollidon 90 F [1] .......2.. II......................................biplanar Hardness ............. 3..... 1 No........................ mix and press with medium to high compression force (20 kN).... dry and pass through a 0...2 % 800 mg 12 mm biplanar 180 N 8 – 9 min 0........................... 2....q.....0........– III...........................12 mm Form ...............85 N Disintegration .......9 Tablet formulations (Lab Scale) Calcium Phosphate Tablets for Cats and Dogs (400 mg) 1................................................ 1 No..........Manufacturing (Direct compression/Wet granulation) Formulation No.........1 min Friability ... add III and press with medium to high compression force (20 kN)....................................................... 2 Dicalcium phosphate [9] ..............................................................s.20 g Water ............8 mm sieve........1% BASF Fine Chemicals Generic Drug Formulations 1998 ....................... Magnesium stearate [2] ...800 mg Diameter ............................. 2 Weight ..s................... 30 g – 150 4g I...100 g Citric acid crystalline ............................

.................................91 Kollidon CL [1] ....2 g g g g 2............... Manufacturing (Direct compression) Mix all components..............................................................................2 Magnesium stearate [2] ....122 mg Diameter ......8 mm sieve and press with medium compression force.......................49 N Disintegration ......1 min Friability........2................8 mm Form .............2 % BASF Fine Chemicals Generic Drug Formulations 1998 .................... 3....................................biplanar Hardness.........25 Ludipress [1] ....................................................................................0..... Formulation Captopril...................... pass through a 0......................9 Tablet formulations (Lab Scale) Captopril Tablets (25 mg) 1...... Tablet properties Weight ..............................................................

.........................8 mm sieve and press with low compression force...................................86 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........200 g Ludipress [1] .................9 Tablet formulations (Lab Scale) Carbamazepine Tablets (200 mg) 1....2 g 2...................................................................2........................ Formulation Carbamazepine .................................. Tablet properties Weight .........75 % 30 min: ..................................................... Manufacturing (Direct compression) Mix all components....496 mg Diameter .........................................83 % 60 min: .................................................................128 N Disintegration .....biplanar Hardness ..... pass through a 0.300 g Magnesium stearate [2] ............................................................0....1 min Friability................... 3.........3 % Dissolution 10 min:..........12 mm Form ...............

...5 mg) 1..95 N Disintegration...............................................................5 Ludipress [1] ...2 – 3 min Friability....2................................0 Copper sulfate.....................24...................................biplanar Hardness................. mix and press with medium compression force..........131 mg Diameter ...2............................................................0 Magnesium stearate [2]...0...........16 Manganese sulfate ..0 g g g g g 2.............9 Tablet formulations (Lab Scale) Carbonyl Iron + Copper Sulfate + Manganese Sulfate Tablets (24 mg + 0.............3........................ Tablet properties Weight ........................................................................8 mm Form .............. 3.... Formulation Carbonyl iron OF (BASF) ..3 % BASF Fine Chemicals Generic Drug Formulations 1998 .........................16 mg + 3.................5 mm sieve..0...............100. Manufacturing (Direct compression) Pass all components through a 0..

... Carnitine .. stir well and add solution II (60 °C).... Preservative .... Manufacturing Heat the mixture I to 60 °C..4 g II...4 g III....................s...... Cool and dissolve III......8 Liquid Formulations (Lab scale) Carnitine + Coenzym Q Solution (4............... colourless liquid..1 g Cremophor RH 40 [1] ..........................0 g 2...........4.........0 % + 0................ Water................ Coenzym Q 10 ...... BASF Fine Chemicals Generic Drug Formulations 1998 ...................95.....0..........1 g Lutrol E 400 [1]..............5...1%) 1......... 3........0.............q........ Formulation I........... Properties of the solution Clear.......... 4................. Physical stability (6–8 °C) No change of clarity after one month...0......

... Manufacturing (Wet granulation) Granulate I with soluton II..... Sodium chloride ........< 0..............................biplanar Hardness .................... Tablet properties Weight ..........2..... III........................ II.... dry........................000 mg Diameter .................2............884 g Kollidon CL [1] .............s.......93 g 2................................20 mm Form ...............93 g Polyethylene glycol 6000.................................................................q...9 Tablet formulations (Lab Scale) Caroate Dispersible Cleaning Tablets (880 mg) 1.... 3...............< 30 sec Friability ......... powder . mix with the components III and press to tablets.. pass through a 0............... Formulation I...................47 g Ethanol or Isopropanol............1% BASF Fine Chemicals Generic Drug Formulations 1998 ............130 N Disintegration (water)............................ Caroate...884 g Kollidon VA 64 [1] .......................................8 mm sieve............................................

........................2 min Friability....000 mg Diameter ................49 g Ethanol or Isopropanol............. Sodium chloride ...............................................20 mm Form ........9 Tablet formulations (Lab Scale) Caroate Effervescent Cleaning Tablets (650 mg) 1.................................................. Formulation I...................140 N Disintegration (water) .............................0. II.......... 3...325 g Sodium bicarbonate .................... Caroate......650 g Tartaric acid ... Tablet properties Weight .........s.q..........................407 g Polyethylene glycol 6000..2.....488 g Kollidon VA 64 [1] ...........................81 g 2.....2........................................ pass through a 0........ powder .........3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........biplanar Hardness ....................................... dry................. mix with the components III and press to tablets......................................8 mm sieve........... III............. Manufacturing (Wet granulation) Granulate I with soluton II...........................

....... Cremophor EL [1] .............................................55 N Disintegration ..........15 g Isopropanol ....................................575 ml III....................... Dry the obtained tablets.... Merck) Bolus alba (Merck) ........................................38 g Water + isopropanol (10 + 3).............150 g II........... 3.................481 mg Diameter ................... Activated charcoal ............28 g Acacia gum...... Manufacturing (Wet granulation) Granulate mixture I with solution II......... dry until the relative powder humidity of 90 % is reached.250 g (Carbo medicinalis................................. add solution III and pass again through a sieve...........300 ml 2. Formulation I.........9 Tablet formulations (Lab Scale) Charcoal Tablets (250 mg) 1..................... Tablet properties Weight ......biplanar Hardness......................................................... pass through a 1 mm sieve.....................12 mm Form ........................................ Dry the granules and press with low compression force...2..........................................1 min BASF Fine Chemicals Generic Drug Formulations 1998 . Kollidon 25 [1] ...............

........3................. Water ..s..........0 g Kollidon 25 [1] .................. cool................. Properties Clear colourless solution having a low viscosity..q...0 g Preservative ...0 g 2.. Formulation Chloramphenicol ................5... dissolve Kollidon 25........... BASF Fine Chemicals Generic Drug Formulations 1998 ......... Manufacturing Dissolve the preservative in hot water....15................ Remark To prevent of discolouration of Kollidon in the solution during storage 0....5 % of cysteine could be added as antioxidant.....add 100.........2 to 0... 4.... 3...............8 Liquid Formulations (Lab scale) Chloramphenicol Ophthalmic Solution (3 %) 1..... add chloramphenicol and stir until a clear solution is obtained..

.......0 g II....2.....8 Liquid Formulations (Lab scale) Chloramphenicol Palmitate Oral or Topical Emulsion (2....5 % = 250 mg/10 ml) 1... Fill up with III to 100 ml..... Properties White......0 g III.... Water.........ad 100 ml 2........................0 g Cremophor RH 40 [1] ......... Sucrose......................5 g Lutrol E 400 [1].. homogeneous emulsion without foam formation.. 3................5...... BASF Fine Chemicals Generic Drug Formulations 1998 ... Cool to 40 °C and add this solution slowly to the well stirred solution II..................40...........40......................... Chloramphenicol palmitate...................... crystalline .......0 g Water.. Manufacturing Mix components I at 70°C to obtain a clear solution.............4......4........ Formulation I......

.5 g Lutrol E400 [1] .......................45 g 2............. Physical Stability After 3 weeks at room temperature and at 45 °C no change of appearance and viscosity was observed....... milky emulsion 4...........s...... Manufacturing Mix components I at 70°C to obtain a clear solution and cool to about 40 °C....4 g Sucrose.............. Formulation I.............................q.....0 % = 500 mg/10 ml) 1............. crystalline .... II. Properties White........5................................................40 g Preservative ................ Water.... BASF Fine Chemicals Generic Drug Formulations 1998 .... 3..6 g Cremophor RH 40 [1] ......... Add the warm solution II slowly to the well stirred solution I.............................8 Liquid Formulations (Lab scale) Chloramphenicol Palmitate Oral or Topical Emulsion (5....... Chloramphenicol palmitate.

.46 g g g g 2.............. 4.30 Lutrol F 127 [1] ...... BASF Fine Chemicals Generic Drug Formulations 1998 .............. 40 °C) No change of the appearance........22 Water..............7 Formulations of semi-solid drugs (Lab scale) Chlorhexidine Gel (2 %) 1......... Maintain the temperature until the air bubbles escaped...2-Propylene glycol Pharma [1] ............ 3.... Physical stability (4 months................................ Manufacturing Dissolve chlorhexidin diacetate in propylene glycol at > 70 °C.................... Properties of the gel A clear colourless gel is obtained. Formulation Chlorhexidin diacetate .2 1.. stir well and add slowly Lutrol F 127 and water.................6..

...... 5........ 5...0 Magnesium stearate [2] .. 5......................... Kollidon VA 64 [1] ................ 63 N Disintegration... 5....0 Eucalyptol.. Formulation Chlorhexidine (Sigma) .............................................8 mm sieve and press with medium compression force..0 Aspartame.......... Manufacturing Mix all components... potassium ............................... 0.......0 Sorbitol........ 0......... Tablet properties Weight...3 % BASF Fine Chemicals Generic Drug Formulations 1998 ............... crystalline ..... crystalline [10] .............................9 Tablet formulations (Lab Scale) Chlorhexidine Lozenges (5 mg) 1.......0 Saccharin.......................................... 175 mg Diameter .0 Menthol........ biplanar Hardness................................................. 1................1 Aerosil 200 [4] ........................................................... 2............ 150....... 3.......... crystalline .................................... 8 mm Form ..... 1.......... sodium ........................................... > 10 min Friability ...............0 g g g g g g g g g 2................2........ pass through a 0.....

...... Kollidon 30 [1] ..............................................202 N Disintegration ........................ Kollidon CL [1].....................................................................................................................100 g II......................8 min Friability ................... 3... Tablet properties Weight ......... Chloroquine diphosphate ........2 g Talc [10] ....................................2....................................................... dry... Ditab [9] .................83 g III..........10 g Aerosil 200 [4] .........biplanar Hardness................................... pass through a 0..3 g 2...... add the mixture III and press with low compression force.......250 g Dicalcium phosphate...........................8 mm sieve..............< 0.........8 mm Form ..361 mg Diameter ...................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...............10 g Isopropanol........................ Manufacturing (Wet granulation) Granulate mixture I with solution II.............9 Tablet formulations (Lab Scale) Chloroquine Tablets (250 mg) 1... Formulation I................

.............................................................< 0...................70 N Disintegration ... 3.............100 g Ludipress [1] ....................................... Tablet properties Weight ..............1% BASF Fine Chemicals Generic Drug Formulations 1998 ....................................350 mg Diameter ................................... Formulation Choline theophyllinate ..................4 min Friability .........................................244 g Magnesium stearate [2] .......5 mm sieve mix and press with very low compression force........biplanar Hardness.. Manufacturing (Direct compression) Pass all components through a 0.......................................9 Tablet formulations (Lab Scale) Choline Theophyllinate Tablets (100 mg) 1..8 mm Form .............................2.............................6 g 2......

.........................................8 mm screen and press with low compression force.71. pass through a 0..8 mm Form ..................... Formulation Chymotrypsine .....................2.....67 N Disintegration .....biplanar Hardness....5 g Ludipress [1] .....................................< 0..6 min Friability ............5 g Magnesium stearate [2]..1....................... Tablet properties Weight ...................100 mg Diameter .........................27....................................9 Tablet formulations (Lab Scale) Chymotrypsine Tablets (27 mg) 1...........................................0 g 2..................................................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ........... 3........... Manufacturing (Direct compression) Mix all components.......................

.............8 mm screen and press with low compression force......................................... Tablet properties Weight ................................biplanar Hardness..............2 % Dissolution (15 min) ........................................... Manufacturing (Direct compression) Pass the mixture through a 0........................................200 g Ludipress [1] .....295 g Magnesium stearate [2] .......................................1 min Friability..5 g 2........................92 N Disintegration ....................................... 3..............................................................510 mg Diameter ...........88 % BASF Fine Chemicals Generic Drug Formulations 1998 ....12 mm Form .........2.0.......................9 Tablet formulations (Lab Scale) Cimetidine Tablets (200 mg) 1.................... Formulation Cimetidine................................

........................14 Water.......................... Kollidon 30 [1] ............. 3..........108 N Disintegration ............................... Magnesium stearate [2] ..................122 II...........................0...................8 mm sieve............................................ Tablet properties Weight ..............288 Corn starch [3] ................ Manufacturing (Wet granulation) Granulate mixture I with solution II...biplanar Hardness .....9 Tablet formulations (Lab Scale) Cimetidine Tablets (280 mg) 1............................12 mm Form ........................ Formulation I......................................................2 g g g g g 2....... add III and press to tablets with low compression force............... pass through a 0.................................3 min Friability...................427 mg Diameter ............................................72 III....2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...2................ Cimetidine.....................

................................ Kollidon VA 64 [1] ..................................................................... add III and press to tablets with low compression force................5 % Dissolution (10 min) .......... Tablet properties Weight ........400 Corn starch [3] ......100 % BASF Fine Chemicals Generic Drug Formulations 1998 ...biplanar Hardness...............170 II..........................................................62 % (20 min) ........ pass through a 0......................................601 mg Diameter ............................................ Magnesium stearate [2] . Manufacturing (Wet granulation) Granulate mixture I with solution II........................................ Cimetidine.....2.... Formulation I.......8 mm sieve.............................................................................................4 min Friability...20 Water ...................................3 g g g g g 2..........91% (30 min) .....9 Tablet formulations (Lab Scale) Cimetidine Tablets (400 mg) 1.................................12 mm Form .0...........................................91 N Disintegration ..... 3.............100 III...........

....9 Tablet formulations (Lab Scale) Clenbuterol Tablets (20 µg) 1............3 min 4.....100 mg Diameter ...................biplanar Hardness......................02 g Ludipress [1] .........................75 N Disintegration .... BASF Fine Chemicals Generic Drug Formulations 1998 ........................................99....... Formulation Clenbuterol hydrochloride ..............0.............. Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of clenbuterol hydrochloride with a small part of the Ludipress before mixing with the other components of the tabletting mixture............2.........8 mm Form ......................00 g Magnesium stearate [2]...................1....... Manufacturing (Direct compression) Mix all components in a turbula mixer and press to tablets with a compression force of 20 kN.......................................... Tablet properties Weight ........... 3....00 g 2..................................................

0 Magnesium stearate [2]...< 1 min Friability ..............................0 Kollidon VA 64 [1] .... Formulation Clobazam..........5 g g g g g 2...........165 mg Diameter ................................1.........0 Dicalcium phosphate DI-TAB [9] ..........................0 Kollidon CL [1]......135......7......................44 N Disintegration ....................8 mm Form ...................................... pass through a 0...............biplanar Hardness....2.......................8 mm sieve and press with medium compression force (15 kN)............< 0....................9 Tablet formulations (Lab Scale) Clobazam Tablets (10 mg) 1.....................1% BASF Fine Chemicals Generic Drug Formulations 1998 .............................. Manufacturing (Direct compression) Mix all components........................ 3.................................................. Tablet properties Weight ..........7.....................10.....................

...............................................13 % Dissolution (60 min) ........................0.......................8 mm Form ............... Manufacturing (Direct compression) Mix all components.............1 mg 2............biplanar Hardness..................................9 Tablet formulations (Lab Scale) Clomifen Citrate Tablets (50 mg) 1.................... Tablet properties Weight ........................2........... 3.................................................................................100 mg Magnesium stearate [2].......................................154 mg Diameter ..............50 mg Ludipress [1].100 % BASF Fine Chemicals Generic Drug Formulations 1998 ......................82 N Disintegration ................. sieve and press with low compression force............6 min Friability .......... Formulation Clomifen citrate ....................

..... Manufacturing Dissolve Closantel in solution II and add solution III.0 – 20.0..... 20 min) 3... Formulation I..5 – 3.... Remarks The function of Kollidon 12 PF or Kollidon 17 PF is to reduce strongly the local side effects (e....... formation of oedemas) and to increase the retention time in the tissue.. Properies of the solution Clear yellow solution 4.0 –12..............ca.0 g Propylene glycol Pharma [1] ..ca...........9. II....0 g Sodium hydroxide..... 50 % in water .....12........g.... Closantel ....0 g Kollidon 12 PF or Kollidon 17 PF [1] .....................8 Liquid Formulations (Lab scale) Closantel Veterinary Injectable Solution (12 – 20 g/100 ml) 1.2.5. 20 g 2..01 – 0. The sterilisation can be done by heating (120 °C... BASF Fine Chemicals Generic Drug Formulations 1998 . Sodium bisulfite ... 60 g III.......04 g Water for injectables ..............

...................30......... II... stir strongly and add slowly the hot solution II.............. s..... Clotrimazol.... Manufacturing Dissolve Clotrimazol in Cremophor RH 40 at about 60 °C.... 3..................33 g 2. Ethanol 96 % . colourless...... BASF Fine Chemicals Generic Drug Formulations 1998 ...................................0 g Cremophor RH 40 .34 g Water............... Properties Clear...... viscous liquid..............q....0 g Preservative . Formulation I.3.........8 Liquid Formulations (Lab scale) Clotrimazol Topical Solution (3 %) 1....................................................................5......

..............................................5 Liquid paraffin ....0.68.........1.8...8 III. 5............................. Properties White cream.........0 Parabene(s)......7............12...................1... Remark This formulation could be used for other active ingredients too........................................2 II............. Add the water II to the obtained solution I with rigorous stirring.............6................. Physical stability No change of appearance or crystallization were observed during 6 weeks at 45 °C... Water. Propylene glycol [1] ........... Heat III until the active ingredient is dissolved...... Cetylstearyl alcohol...................0 Clotrimazole ... 3...0 Cremophor A 6 [1] .....5 Cremophor A 25 [1] ...........0 g g g g g g g g 2... BASF Fine Chemicals Generic Drug Formulations 1998 .... 4. Formulation I... Manufacturing Heat the mixture I and the water II separately to about 80 °C....................1.....................7 Formulations of semi-solid drugs (Lab scale) Clotrimazole Cream (1%) 1....... mix with I/II and continue to stir during cooling to room temperature.

.......s.....................................1000 g (Kollidon CL-M........................biplanar Hardness ...............65 g 2......................q............................................................ micronized .........2......... Tablet properties Weight ...........125 g Flavour mixture..... pass through a sieve. Manufacturing (Wet granulation) Granulate mixture I with solution II..........25 g II............. crystalline.... Magnesium stearate [2] ..............................................1 min Friability.............. 3..... Crospovidone...........................................................................9 Tablet formulations (Lab Scale) Crospovidone Effervescent Tablets (1000 mg) 1.. BASF Fine Chemicals Generic Drug Formulations 1998 ............................... Remark The dosage may be increased to 2000 mg crospovidone by increasing the tablet weight to 3200 mg......................150 g Aerosil 200 [4] ............ Formulation I.......................1590 mg Diameter .. Sucrose............................... III................. BASF) Citric acid......100 g Saccharin sodium.............................................1 g Water....................111 N Disintegration .............. mix the dry granules with III and press with medium compression force..........20 mm Form ..........0..................5 g Sodium bicarbonate.......................4 % 4..

...... 3................ Manufacturing (Wet granulation) Granulate mixture I with solution II......1 – 2 min Friability ....... Formulation I............................................250 Saccharin sodium.................2........2-3 Water.....................20 mm Form ............................ Remark The dosage may be increased to 2000 mg Crospovidone by increasing the tablet weight to 2600 mg...................1280 mg Diameter ..............................50 II..........................................6 % 4......5 g g g g g g g 2.... pass through a sieve. Tablet properties Weight ......5 Flavours ....... Magnesium stearate [2] .............. Crospovidone M (BASF) ..............380 III.........................................0.......................................................103 N Disintegration........9 Tablet formulations (Lab Scale) Crospovidone Water Dispersible Tablets (1000 mg) 1................. crystalline ..............................1000 Aerosil 200 [4] ............................................................. BASF Fine Chemicals Generic Drug Formulations 1998 ................................ mix the dry granules with III and press with low compression force......................... Sucrose..biplanar Hardness .....

...biplanar Hardness.......................... BASF Fine Chemicals Generic Drug Formulations 1998 .. Manufacturing (Direct compression) Pass all ingredients through a 0.............202 mg Diameter .................... Formulation Cyproheptadine ...................................................................................... Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation.........................46 N Disintegration ............ 3 min Friability............4 g Ludipress [1] ........................194 g Magnesium stearate [2] ....2 g 2...................5 % 4........................... Mix and press with very low compression force (4 kN)....... 3..........................0......8 mm sieve..............................2..................9 Tablet formulations (Lab Scale) Cyproheptadine Tablet (4 mg) 1.....................8 mm Form ....................... Tablet properties Weight ..............

...................... Cool to room temperature stirring continously when the air bubbles disappeared.6............ 4...... Physical stability (3 months........................... Formulation Dexpanthenol (BASF)................7 Formulations of semi-solid drugs (Lab scale) Dexpanthenol Gel-Cream (5 %) 1. 3....... BASF Fine Chemicals Generic Drug Formulations 1998 .............15 Lutrol F 127 [1] ...................... 40 °C) No change of the appearance and viscosity............... Properties of the gel Soft turbid gel-cream.....52 g g g g g 2.........................................10 Lutrol E 400 [1].. Manufacturing Dissolve dexpanthenol and Lutrol E 400 in water...... add liquid paraffin and stir heating to 60 – 70°C.......... Add slowly Lutrol F 127 and stir until it is dissolved..18 Water................5 Liquid paraffin .......

................................... 3.......... stirr well and add very slowly the hot solution II................... Diazepam..8 Liquid Formulations (Lab scale) Diazepam Injectable Solution (2.00 g Water for injectables ... Formulation I............. II..................... BASF Fine Chemicals Generic Drug Formulations 1998 ...0..s...ad 100 ml Preservative ....................5..........................5 mg/ml) 1........ 2....... Properties of the solution A clear colourless solution of very low viscosity was obtained........4............4....00 g Lecithin ....q.......25 g Solutol HS 15 [1] .. Manufacturing Heat mixture I to 60 – 70 °C............

...........................5 – 2......................... 3...........................................8 mm sieve and press with medium compactation force.............................................9 Tablet formulations (Lab Scale) Diazepam Tablet (10 mg) 1........0 g 2................110 – 490 mg ......> 100 N Disintegration ...............1% Dissolution (10 min) .100 % BASF Fine Chemicals Generic Drug Formulations 1998 . pass through a 0............................ Manufacturing (Direct compression) Mix all components......< 5 min Friability .................10 g Ludipress ...................... Formulation Diazepam..............................................................................100 – 480 g Magnesium stearate .......according to the formulation Form ....biplanar Hardness .....< 0...............0.. Tablet properties Weight .......................................2.

........................... Maintain the temperature until the air bubbles disappeared.... Manufacturing Dissolve Lutrol F 127 in water at 4 – 6 °C (or at > 70 °C) and mix with the solution of diclofenac sodium in propylene glycol.............. Formulation Diclofenac sodium .......... 3......... BASF Fine Chemicals Generic Drug Formulations 1998 .........................22 Water.....6....7 Formulations of semi-solid drugs (Lab scale) Diclofenac Gel (1%) 1.........57 g g g g 2.1 Propylene glycol Pharma [1] ......... Properties Colourless clear gel.................................................20 Lutrol F 127 [1] ..

..............1 Propylene glycol Pharma [1] ....................10 Lutrol F 127 [1] ... Manufacturing Dissolve diclofenac sodium in propylene glycol....6.. Properties White..15 Miglyol ® 812 (Dynamit-Nobel) ........................7 Formulations of semi-solid drugs (Lab scale) Diclofenac Gel-Cream (1%) 1.......... Dissolve Lutrol F 127 in this well stirred mixture at 4 – 6 °C (or at > 70 °C). turbid gel-cream...... BASF Fine Chemicals Generic Drug Formulations 1998 .. Formulation Diclofenac sodium ..20 Water.................. Maintain the temperature until the air bubbles escaped................ 3................................ add the mixture of water and Miglyol 812.....54 g g g g g 2...............................

50...2 µm)........0 g Kollidon 17 PF [1] ...............8 Liquid Formulations (Lab scale) Diclofenac Injectable Solution (75 mg/3 ml) 1........... BASF Fine Chemicals Generic Drug Formulations 1998 ..........................5.... add diclofenac sodium and stir until a clear solution is obtained............5...............5 g Propylene glycol Pharma [1] ...... The sterilisation could be made by aseptic filtration (0....0 g Water for injectables...... Manufacturing Dissolve Kollidon 17 PF in the mixture of propylene glycol.. benzyl alcohol and water........................12..to 300 ml 2.7.......0 g Benzyl alcohol .......... Formulation Diclofenac sodium .................

.........8 Liquid Formulations (Lab scale) Diclofenac Oral Solution (1......0 g Water .5 1........5.................................5 g g g g g 2.............5 40.........– Sucrose.0 g No. 2 1...0 56.....1...56.. 1 Diclofenac sodium..... Manufacturing Dissolve diclofenac sodium in the aqueous solution of the auxiliaries............ BASF Fine Chemicals Generic Drug Formulations 1998 ...................... crystalline ...40.....5 0..2.. Physical stability There was no crystallisation after the storage of 2 weeks at 6 °C....................5 %) 1. 3................5 g Cremophor RH 40 [1] ............. Formulations No......5 g Kollidon 30 [1]...........................................

.... add III and press with low compression force......10 g Magnesium stearate [2] ...........132 g Kollidon 30 [1] .........................q...72 N Disintegration ............... Diclofenac sodium (Chemag).8 mm sieve..................209 mg Diameter .................................................6 g II........................ Formulation I...................... 3............. Ethanol 96 % .........4 % BASF Fine Chemicals Generic Drug Formulations 1998 ..7 min Friability.............................. III..9 Tablet formulations (Lab Scale) Diclofenac Tablet Cores (50 mg) 1....2 g 2.biconvex Hardness........50 g Calcium phosphate................... dibasic [9]............................................. Manufacturing (Wet granulation) Granulate mixture I with solvent II.........................................................2.....0................... pass through a 0...................................................s...................................... Kollidon CL [1]......8 mm Form .................... Tablet properties Weight ....

....................9 Tablet formulations (Lab Scale) Diclofenac Tablets (50 mg) 1.....................0 g 2......biplanar Hardness.....0 g Kollidon CL [1] ..15....99 % BASF Fine Chemicals Generic Drug Formulations 1998 .150.1% Dissolution (10 min) .58 % (15 min) ................................0 g Ludipress [1] ......<0.......................................................................0 g Magnesium stearate [2]...10......... 3.....77 % (30 min)................................16 min Friability . Formulation Diclofenac sodium ...................................................5 g Polyethylene glycol 6000.......... pass through a 0.72 N Disintegration ...................................................................226 mg Diameter ................................... Manufacturing (Direct compression) Mix all components..................................................................................1..... powder [6] ........2. Tablet properties Weight ..........................8 mm sieve and press with low compression force...................................8 mm Form ............50.....

................................1 g Magnesium stearate [2] ..............biplanar Hardness ........ Manufacturing (Direct compression) Mix all components........................................ powder [6].......8 mm Form ..................2................................9 Tablet formulations (Lab Scale) Diltiazem Tablets (50 mg) 1...................................... Tablet properties Weight .......................................1 g 2............... Formulation Diltiazem ................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...5 g Aerosil 200 [4] .........................60 g Ludipress [1] ............................ pass through a sieve and press with low compression force....................................> 100 N Disintegration .........141 g Polyethylene glycol 6000..215 mg Diameter ...................................6 min Friability .......... 3.............................................................0.........

...................................................................2 g g g g g g g g g 2......16 Aerosil 200 [4] ...1% BASF Fine Chemicals Generic Drug Formulations 1998 ............................2....9 mm Form ....................40 Corn starch [3] . Tablet properties Weight .................8 mm sieve........ Dimenhydrinate . mix with III and press with low compression force... Manufacturing (Wet granulation) Granulate mixture I with solution II......210 mg Diameter ....................................... Formulation I.............................................................................40 Kollidon 90 F [1] .................< 1 min Friability..........................14 Talc [10] ...............................................6 II.. dry.................................................................biconvex Hardness ..........................................................9 Tablet formulations (Lab Scale) Dimenhydrinate Tablet Cores (100 mg) 1......................... 3...100 Lactose monohydrate [8] .. pass through a 0......30 III.......... Isopropanol............................27 N Disintegration ..............................................2 Calcium arachinate [2] .................................. Kollidon CL [1]........................

............................300 mg Diameter .. Tablet properties Weight .................10 min Friability............144 N Disintegration ..........................................2.......................................................................9 Tablet formulations (Lab Scale) Dimenhydrinate Tablets (50 mg) 1...........................................50 g Ludipress [1] ........................................... sieve and press with low compression force..5 g 2..5 % BASF Fine Chemicals Generic Drug Formulations 1998 ........8 mm Form ......... 3....................................0.....245 g Magnesium stearate [2] ........... Formulation Dimenhydrinate ...............................biplanar Hardness ................................ Manufacturing (Direct compression) Mix all components.................

...............................0 bar Type of spraying .......................................................– Water.....continuous Inlet air temperature ......... Formulations No......................– Silicone emulsion ..... II.................................... Coating procedure (Accela Cota 2499) Tablet core loading ...100 g Kollicoat MAE 30 DP [1].............. 3................................................................3.....................5 g Propylene glycol Pharma [1]..................................12 rpm Spray nozzle......9 mg Quantity of film-forming agent/cm 2 ..............approx.............5 Coating formulations (Lab Scale) Enteric Film Coating 1......................... 30 °C Spraying time ....................................... Manufacturing of the suspension Prepare the suspensions I and II separately.....................5 g Talc [10] ........................... Sicovit Titanium dioxide [1] ................................. mix both and homogenize in a disk mill or in a colloid mill....2............5 kg Core size ....................................approx................. 60 min Spraying rate............0........5 g Kollidon 25 or Kollidon 30 [1] .....1..............20 g Sicovit Iron oxide Red 30 [1] ...350 g No..................................... 1 I........... 30 g/min BASF Fine Chemicals Generic Drug Formulations 1998 .9 mm biconvex Quantity of suspension applied..6 mg Speed of the coating pan ...................approx..........................................890 g Quantity of solids/cm2 ......500 g Triethyl citrate (Merck)....................8 mm Spraying pressure ........50 °C Outlet air temperature ... 2 10 90 10 12 6 2 420 200 g g g g g g g g – 400 g 2......................................15 g Water .........

...................................................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...9 Tablet formulations (Lab Scale) Ephedrine Tablets (100 mg) 1..............524 mg Diameter ...............397.....100.......7 min Friability ....... Formulation l-Ephedrine hydrochloride (Knoll) ............................biplanar Hardness ......5 g 2........................................................> 150 N Disintegration ................................2......... Manufacturing (Direct compression) Mix all components.0..................... Tablet properties Weight .12 mm Form ..................................8 mm sieve and press with medium compression force...............0 g Ludipress [1]....................2...............5 g Magnesium stearate [2]......... 3.......... pass through a 0...

.....20 III. Manufacturing Heat solution I to about 70 °C....39 g g g g g 2........................20 II.................20 Propylene glycol Pharma [1] . 3...................... Erythromycin base....................... Properties of the gel A clear soft gel is obtained........1 Lutrol E 400 [1].......................... Formulation I......6............... dissolve II.......... mix with III and cool when the air bubbles escaped. Lutrol F 127 [1] .........7 Formulations of semi-solid drugs (Lab scale) Erythromycin Gel (1%) 1............................... Water........ BASF Fine Chemicals Generic Drug Formulations 1998 ...

pass through a 0..620 mg Diameter .................................... crystalline [10] .............................................................................8 mm sieve and press with medium/high compression force..10 g g g g g 2....... Manufacturing (Direct compression) Mix all components........................ 3.........................................0..............................................................8 % BASF Fine Chemicals Generic Drug Formulations 1998 ................ DC 1........................................2... Formulation Ethambutol ..................200 Kollidon VA 64 [1] .......12 mm Form ..............................................................10 min Friability...........400 Sorbitol..... Tablet properties Weight ..biplanar Hardness.....................................10 Magnesium stearate [2].......82 N Disintegration..9 Tablet formulations (Lab Scale) Ethambutol Tablets (400 mg)................20 Kollidon CL [1].......

...q...................................9 Tablet formulations (Lab Scale) Ethambutol Tablets (400 mg)..........biplanar Hardness..12 mm Form .......................s. IV........................10 g 2........................2............................................622 mg Diameter .................. dry........ Tablet properties Weight ...................................................... Formulation I......... Manufacturing (Wet granulation) Granulate mannitol II with solution III.............. WG 1......7 g Water............9 min Friability........97 N Disintegration ..........200 g III..4 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................... 3...........................................400 g Kollidon CL [1] ............................................. Ethambutol .......... Mannitol....................0........................................................ pass through a 0.................... mix with the components I and IV and press with high compression force....40 g II........................... Magnesium stearate [2]........8 mm sieve......... Kollidon 30 [1] ......

.. Tablet properties Weight ................................ Ethambutol (Helm) .......................30 g Isopropanol .............................................2.....oblong Hardness...........................................78 N Disintegration ..... 3.......800 g Dicalcium phosphate......................................1.............. Formulation I....9 Tablet formulations (Lab Scale) Ethambutol Tablets (800 mg) 1................2 min Friability ........ DI-TAB [9] ....................................................50 g Magnesium stearate [2].............200 g II....... Kollidon 30 [1] ... Kollidon CL [1] ............................15 g 2.............q.....................................112 mg Diameter .1% BASF Fine Chemicals Generic Drug Formulations 1998 .....8 mm sieve.... add III and press with high compression force.............................. III.............. Manufacturing (Wet granulation) Granulate mixture I with solution II. pass through a 0.....1.........................20 mm Form .. dry.......................s...............

.....................101 g Theophylline....7 – 8 min Friability....................102 N Disintegration...2.............biplanar Hardness .............. anhydrous 0............................. BASF Fine Chemicals Generic Drug Formulations 1998 . DC 1......... 3... pass through a 0.................................... powder (Knoll) ....................23 g Ludipress [1] .............2 g 2...................... Remark To enhance the flowability of the tabletting mixture the amount of Aerosil 200 could be increased.......2 % 4......2/0.............................................................................175 mg Diameter ...........1 g Aerosil 200 [4] .......................... Formulation Etophylline...........8 mm Form .....................53 g Magnesium stearate [2] .........8 mm sieve and press to tablets with low compression force............ Manufacturing (Direct compression) Mix all components....0........ Tablet properties Weight .7 (Knoll) .....................9 Tablet formulations (Lab Scale) Etophylline + Theophylline Tablets (100 mg + 22 mg)..............................

................................ pass through a 0...........................7 (Knoll) ...8 mm Form ......100 g Theophylline...........3 g II...50 g Kollidon VA 64 [1] ..........................92 N Disintegration ..23 g Corn starch or potato starch .. Kollidon VA 64 [1] ..183 mg Diameter ........... WG 1.. Etophylline..3 – 4 min Friability.........3 % BASF Fine Chemicals Generic Drug Formulations 1998 .................................................5 mm sieve and press with medium compression force............ 3...4 g Water.............................. powder (Knoll) ....................................... Formulation I...................................35 g III........ Manufacturing (Wet granulation) Granulate mixture I with solution II................................... anhydrous 0.. dry................5 g 2......................9 Tablet formulations (Lab Scale) Etophylline + Theophylline Tablets (100 mg + 22 mg)........... Tablet properties Weight ......2..............................8 mm sieve.................... mix with III...........2/0......................0........................1 g Talc [10] ...... Magnesium stearate [2] ...................................................biplanar Hardness..... pass through a 0.....

.......... Water.......ad 100 ml 2........s................8 Liquid Formulations (Lab scale) Eucalyptol Solution (8 %) 1.......................... Properties of the solution Clear or slightly opalescent................. Eucalyptol ............0 g Cremophor RH 40 [1] . stir well and add slowly the warm solution II......... colourless liquid..... Formulation I....0 g Preservative ......... 3.................................... BASF Fine Chemicals Generic Drug Formulations 1998 ........ Manufacturing Mix eucalyptol and Cremophor at 65 °C.....4......q..8...5. II....

....– Aerosil 200 [4]........................... pass through a 0... 1 No........................................................74 N Disintegration (gastric juice)............................................................1% Dissolution (10 min)............. 1 No..............................biplanar Hardness ...... 2 Weight ....2......................................3 min Friability.....................................................9 Tablet formulations (Lab Scale) Famotidine Tablets (40 mg) 1...................... 2 Famotidine..8 mm Form ...63 % (30 min) ....................3 % not tested not tested BASF Fine Chemicals Generic Drug Formulations 1998 .....................................8 mm sieve and press with low compression force.............................3 g Stearic acid [7] .................................95 % 148 mg 8 mm biplanar 49 N 1 min 0.......... Tablet properties No.................................................................<0.....................149 mg Diameter . 3.105 g Magnesium stearate [2] .................. Formulations No.................. Manufacturing (Direct compression) Mix all components........4 g 40 g 104 g – 2g 4g 2...40 g Ludipress [1] ..............................................

........ Manufacturing (Direct compression) Mix all components..................295 g Magnesium stearate [2] ...biplanar Hardness.....................................................................................5 g 2........................................................ Formulation Ferrous fumarate ........................ Tablet properties Weight ..........200 g Ludipress [1] .................2 % BASF Fine Chemicals Generic Drug Formulations 1998 . 3...................................... pass through a 0................12 mm Form ................................................0..92 N Disintegration .........................9 Tablet formulations (Lab Scale) Ferrous Fumarate Tablets (200 mg) 1....509 mg Diameter ....................................8 mm sieve and press with low compression force.2..1 min Friability................

anhydrous ...... Formulation Ferrous sulfate....................................3.........................................4 % BASF Fine Chemicals Generic Drug Formulations 1998 ...65................2..0 g g g g g g g 2..........5 Copper sulfate............3 – 4 min Friability....... mix and press with high compression force............0...........8 mm Form ...................................................................................28 N Disintegration ................ Tablet properties Weight ....................... Manufacturing (Direct compression) Pass all components through a 0........................0 Manganese sulfate ............70............0 Magnesium stearate [2]..........149 mg Diameter .....0..............0 Kollidon 30 [1] ..2..9 Tablet formulations (Lab Scale) Ferrous Sulfate + Manganese Sulfate + Copper Sulfate Tablets (65 mg + 3........................................3.....0 Aerosil 200 [4] .biplanar Hardness.....5 mm sieve.................................................................16 Ludipress [1] ..... 3..................5 mg + 0......................10......16 mg) 1..............................

.. 3..........................0..8 mm sieve and press to tablets with medium compression force......3 g g g g g g 2...................................... Manufacturing (Direct compression) Mix all components....................................................185 Kollidon VA 64 [1] ........................203 Ludipress [1] .......................................................................413 mg Diameter .... Formulation Ferrous sulfate..............................4 Aerosil 200 [4] ........................................ anhydrous ........ pass through a 0..................................................8 mm Form . Tablet properties Weight ..2..............15 Magnesium stearate [2] ...........2 % BASF Fine Chemicals Generic Drug Formulations 1998 .................13 min Friability..............................................4 Talc [10] .............................biplanar Hardness ..110 N Disintegration......................................9 Tablet formulations (Lab Scale) Ferrous Sulfate Tablets (200 mg) 1....................

. Manufacturing Mix the active ingredients with Cremophor RH 40 and heat to 50 – 60 °C.........6........7 g g g g g 2.........5......3 Water.......0 Cremophor RH 40 [1] ................ Add the ethanol and slowly the warm water to the well stirred solution............... 4........5.................0 Ethanol 96 % ..45..0 Camphora.......................... 3..................... BASF Fine Chemicals Generic Drug Formulations 1998 ........... Formulation Fir needle oil (Frey & Lau) ........8 Liquid Formulations (Lab scale) Fir Needle Oil Solution (3 %) 1......3......... Remark The needed amount of Cremophor RH 40 depends on the type of fir needle oil...........40.................. Properties of the solution Clear or slightly opalescent liquid.....

...............1....8 mm Form .......................2.........5............... Manufacturing (Direct compression) Mix all components........................................................ pass through a 0..............0 g Magnesium stearate [2]..............................5 g 2...................9 Tablet formulations (Lab Scale) Folic Acid Tablets (5 mg) 1...........0 g Ludipress [1] .......................................................... 3........................205 N Disintegration .. Tablet properties Weight . BASF Fine Chemicals Generic Drug Formulations 1998 ...7 min Friability ........213 mg Diameter .................................< 0.1% 4......195..8 mm sieve and press to tablets with medium compression force.......................... Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation.................biplanar Hardness.................................... Formulation Folic acid ......

.......... Remark To accelerate the disintegration the amount of Kollidon 90 F should be reduced and Kollidon CL should be applied in intra................125...........................0 g Dicalcium phosphate................. Tablet properties Weight ......................................0 g II.................. Kollidon CL [1] .63.............. BASF Fine Chemicals Generic Drug Formulations 1998 ............. add the mixture III and press with low compression force.......2.......2 g Aerosil 200 [4] .......55 N Disintegration ....................0 % 4.6.....25 min Friability .3 g Magnesium stearate [2]... dry.................. Formulation I.. Kollidon 90 F [1] .............30 ml III... Manufacturing (Wet granulation) Granulate mixture I with solution II.............................. pass through a 0.................................................................8 mm sieve.......200 mg Diameter ..........1.. 3.....................5 g Isopropanol ...... Fucidine ...........0 g 2...............and extragranular form.....................................9 mm Form .....................biconvex Hardness..... DI-TAB [9] ............................2.....................................3............................9 Tablet formulations (Lab Scale) Fucidine Tablet Cores (125 mg) 1......

....................1... 3......00 g Tartaric acid ........2 to 0... BASF Fine Chemicals Generic Drug Formulations 1998 ..25 g Kollidon 12 PF [1] ..... Remark To prevent of discolouration of Kollidon in the solution during storage 0...........8 Liquid Formulations (Lab scale) Furaltadone Injectable Solution (50 mg/ml) 1... 20 min)........... Manufacturing Dissolve the solid substances in water at about 50 °C... The sterilisation can be made by aseptic filtration or by heating (120 °C.........5 % of cysteine could be added as antioxidant..............25................ad 100 ml 2................................00 g Water of injectables .5.. Formulation Furaltadone.5...........

........................................................205 mg Diameter ......................biplanar Hardness..........................................8 mm Form ........81 N Disintegration ...2..............1% BASF Fine Chemicals Generic Drug Formulations 1998 .................................... Manufacturing (Direct compression) Mix all components......................9 Tablet formulations (Lab Scale) Furosemide Tablets (40 mg) 1....................... 3.............. pass through a 0....... Tablet properties Weight ..........8 mm sieve and press with low compression force..............2 g 2......................................................................................0........2 min Friability .... Formulation Furosemide .........................................158 g Magnesium stearate [2] .........40 g Ludipress [1] ...

.................................................. Formulation Furosemide ....................... pass through a 0......................3 – 4 min Friability............................0...............618 mg Diameter ....12 mm Form ....... Manufacturing (Direct compression) Mix all components.....6 g g g g 2.....................159 N Disintegration ........2 % BASF Fine Chemicals Generic Drug Formulations 1998 .............9 Tablet formulations (Lab Scale) Furosemide Tablets (200 mg) 1.........8 mm sieve and press with low compression force... 3............................................. Tablet properties Weight .......................................................................................biplanar Hardness ...............200 Ludipress [1] ...........388 Magnesium stearate [2] .6 Aerosil 200 [4] ....................2.....................................................................

....................23 min Friability.......................9 Tablet formulations (Lab Scale) Garlic Tablets Cores (100 mg) 1.. Manufacturing (Wet granulation) Granulate mixture I with solution II................................... dibasic [9] .............. pass through a 0.......100 Magnesium stearate [2] ............9 mm Form ................................................. Calcium phosphate..94 II....0......... BASF Fine Chemicals Generic Drug Formulations 1998 ......................................... Dried garlic powder .... Kollidon 30 [1] .................biconvex Hardness...2....... Formulation I.......25 III...............9 Water....................... Tablet properties Weight ......................8 mm sieve. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application.................................98 N Disintegration .....................3 % 4............312 mg Diameter . add III and press with low compression force........................................ 3..............95 Lactose monohydrate [8] ........................................................................2 g g g g g g 2.....

...................................................... 3.........7 mm Form .. Tablet properties No............ 1 No.......... Formulation No..............................biplanar Hardness ........................................ 2 Weight ......0 g 2.......................< 0....0 g 1.125 mg Diameter ........– Ludipress [1] ........................................8 mm sieve and press with low compression force (about 10 kN)....80 N Disintegration .....................................50 % (30 min) . Manufacturing (Direct compression) Mix all components..........120.....1% – – – BASF Fine Chemicals Generic Drug Formulations 1998 .........5 g – 5.....................2..................... pass through a 0....................9 Tablet formulations (Lab Scale) Glibenclamide Tablets (5 mg) 1....................75 % 201 mg 8 mm biplanar 107 N 3 – 4 min < 0...............2 % Dissolution (10 min)..............................0 g Magnesium stearate [2] .......0........................................................................... 1 No...........................0 g Glibenclamide ...................69 % (60 min) .........0 g 194.............. 2 Glibenclamide micronized (Guidotti)........5.....2-3 min Friability ....

1% Compression force 10 kN 20 kN 107 N 3 – 4 min < 0.4. 2) Property Hardness Disintegration Friability 5 kN 47 N 2 – 3 min < 0.1% BASF Fine Chemicals Generic Drug Formulations 1998 158 N 3 – 4 min < 0.1% 25 kN 191 N 5 min < 0. Influence of the compression force on the physical tablet properties (Formulation No.1% .

......................... crystalline [10] ........... 3.........................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ..............17 g Water.........................q.......115 g II..................................... Manufacturing (Wet granulation) Granulate mixture I with solution II............719 mg Diameter ..12 mm Form ....................0........................................biplanar Hardness .....................s........................................ Glutaminic acid ............... Formulation I...................138 N Disintegration ....... Press with low compression force to tablets................8 mm sieve and mix with III........................2 g 2............573 g Sorbitol....................................... Kollidon 30 [1] ..... Tablet properties Weight..............6 min Friability.............. dry.......................9 Tablet formulations (Lab Scale) Glutaminic Acid Tablets (550 mg) 1.........11 g Magnesium stearate [2] ........ Kollidon CL [1] .......... III... pass through a 0................................................2..

Manufacturing Mix gramicidin and Cremophor RH 40..... Properties Clear solution.......... BASF Fine Chemicals Generic Drug Formulations 1998 ..1..........q................................ Gramicidin..........0.......98........... heat to about 65 °C.. II.... Formulation I................ s..1 g Ethanol 96 % ...0 g Preservatives..............8 g 2.......... stir and add slowly the heat solution II...8 Liquid Formulations (Lab scale) Gramicidin Ophthalmic Solution (1..3 mg/10 ml) 1.......................5.. Water....13 mg Cremophor RH 40 [1]....................................... 3..........................

.125 g Ludipress [1] ................................... BASF Fine Chemicals Generic Drug Formulations 1998 ....................... powder [6] .......................................................................... Remark The flowability of the tabletting mixture should be increased by higher amounts of Ludipress or/and Aerosil 200. Formulation Griseofulvin.......................biplanar Hardness...........88 % 60 min ..............0.19 g 2........367 mg Diameter ...250 g Polyethylene glycol 6000..............................................9 Tablet formulations (Lab Scale) Griseofulvin Tablets (125 mg) 1............................................79 N Disintegration ........1 min Friability........................................ micronized (Aldrich) ........ mix and press with low compression force applying a vibrating hopper.12 mm Form ..........92 % 4...........2.......... Tablet properties Weight ....................... 20 min .........5 mm sieve. Manufacturing (Direct compression) Pass all components through a 0.........................3 % Dissolution................................. 3...............10 g Aerosil 200 [4] .....................78 % 40 min ....................

........... Kollidon CL [1] ...........................................2 min Friability........5 g g g g g g g 2....................500 Kollidon VA 64 [1] ..............500 III. Tablet properties Weight ................5 Aerosil 200 [4] .........62 N Disintegration ...........................9 Tablet formulations (Lab Scale) Griseofulvin Tablets (500 mg) 1............................. pass the obtained coprecipitate through a 0..............2............. evaporate to dryness............................................... Manufacturing (Wet granulation) Dissolve mixture I in the solvent II................................... 3............751 mg Diameter ..........................................................................7..................0........5 % BASF Fine Chemicals Generic Drug Formulations 1998 ........75 Lactose monohydrate [8] .... Formulation I....................... Dimethyl formamide ..........................................biplanar Hardness.............100 II..........5 mm sieve..................................75 Magnesium stearate [2] .... mix with III and press with low compression force.. Griseofulvin .......12 mm Form ...............

....... Heat to room temperature when the air bubbles escaped........u..ad 100 g 2.......... Add slowly Lutrol F 127 and stir until it is dissolved........................15 g Liquid paraffin ....... add Lutrol E 400 and liquid paraffin.........................................10 g Lutrol F 127 [1] ..................186 mg Lutrol E 400 [1].................................................7 Formulations of semi-solid drugs (Lab scale) Heparin Gel-Cream (300 i............. Formulation Heparin sodium .6........... BASF Fine Chemicals Generic Drug Formulations 1998 ....23 g Water .......... Manufacturing Dissolve heparin sodium in water......./g) 1......... stir and cool to 6 °C.

....................75 N Disintegration...........489 mg Diameter ... pass through a 0.... II.........14 g Lutrol F 68 [1] ............................................. Formulation I........................ mix with III and press with high compression force. powder ...8 mm sieve.......about 120 g III.....s....12 mm Form ............................................................................... Manufacturing (Wet granulation) Granulate the extract I with solution II.... 3.456 g Kollidon VA 64 [1] .2 – 3 min Friability...............5 g Isopropanol .......2 % BASF Fine Chemicals Generic Drug Formulations 1998 .......... 2..................................... Kollidon CL [1]..........14 g Magnesium stearate [2]....9 Tablet formulations (Lab Scale) Horsetail Extract Tablets (450 mg) 1.......................................................................... Tablet properties Weight ............... Horsetail extract..biplanar Hardness..................................q.................... dry...................................2.........................0...........

....< 1 min Dissolution of hydrochlorothiazide.2.....2 g g g g g 2.........9 mm Form ... mix and press.......biconvex Hardness............................................ Manufacturing (Direct compression) Pass all components through a 0....2 Magnesium stearate [2] ........369 mg Diameter . 3.............................................300 Kollidon CL [1].....88 N Disintegration .................................................................................................. Tablet properties Weight ..........................................................................50 Potassium chloride ........................15 Aerosil 200 [4] ....9 Tablet formulations (Lab Scale) Hydrochlorothiazide + Potassium Chloride Tablet Cores (50 mg + 300 mg) 1...........89 % 10 min BASF Fine Chemicals Generic Drug Formulations 1998 ..................................... Formulation Hydrochlorothiazide..................8 mm sieve..............................................

..............................................................................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ............................................2.3 min Friability .. Tablet properties Weight ......................9 Tablet formulations (Lab Scale) Hydrochlorothiazide Tablets (50 mg)................ 3...............2 g 2...................biplanar Hardness.8 mm sieve and press with low compression force...328 mg Diameter .......70 N Disintegration ...............8 mm Form ......0.......................................................... Formulation Hydrochlorothiazide...280 g Magnesium stearate [2] . pass through a 0............................................................................... DC 1........ Manufacturing (Direct compression) Mix all components........50 g Ludipress [1] .........

.. 3...422 g Kollidon 90 F [1] ................... Kollidon CL [1]........ Tablet properties Weight ...............................9 Tablet formulations (Lab Scale) Hydrochlorothiazide Tablets (50 mg)............. pass through a 0.......biplanar Hardness...........55 N Disintegration .... add III and press with low compression force......................................8 mm sieve.............100 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................................................................< 0...15 g Magnesium stearate [2] ..................................12 mm Form ......1% Dissolution (30 min)........................ WG 1.............92 % (60 min) ...50 g Lactose monohydrate [8] ..................................< 1 min Friability ...........................2 g 2.....38 ml III............................................2......................................... Hydrochlorothiazide (Chemag)....................... 2-Propanol ..........495 mg Diameter .................. Formulation I.... Manufacturing (Wet granulation) Granulate mixture I with solution II.................................................8 g II....................

........0 g Cremophor A 25 [1]........0 g – – q.... 1: Suspend I in the mixture II at 70 °C................... Preservative ......................... 2.....0 g 20. dilute with the solution IV..... 3.......7................ 2 Hydrocortisone acetate . Formulations No.........26.....5.............. heat to 70 °C and add slowly to the hot mixture I/II...0 g III... Add solution V and continue to stir until the gel is cool...8 g Water.......... and add slowly to the hot mixture I/II...........49.......... 64. II...q...............................0...........0 g V.... Manufacturing Formulation No. heat to 70 °C..............5 g IV.....10.– Cremophor RH 40 [1] .........................0 g Lutrol E 400 [1]....................................... 1 No........ Carpopol 940 (Goodrich) ................ Continue to stir until the gel is cool.........................................................5 g Water .....7 Formulations of semi-solid drugs (Lab scale) Hydrocortisone Aqueous Gels (1%) 1........... Prepare solution II..0 g – 15. Prepare solution IV. BASF Fine Chemicals Generic Drug Formulations 1998 . Water ..s...............1. Properties Clear colourless gels......... Formulation No. 2: Suspend I in the mixture II at 70 °C..............0 g – – I...........2 g 1..........s............0... Triethanolamine ...............6....

BASF Fine Chemicals Generic Drug Formulations 1998 .......7 Formulations of semi-solid drugs (Lab scale) Hydrocortisone Cream (1%) 1.0 g g g g g g g g 2.......2 II......0 Hydrocortisone.......................... 3.................................0..... Heat III until the active ingredient is dissolved.... mix with I/II and continue to stir during cooling to room temperature...................12....8.....................68.. Remark This formulation could be used for other active ingredients too.....5 Liquid paraffin ...1.. Propylene glycol [1] .. Manufacturing Heat the mixture I and the water II separately to about 80 °C..1........... Cetylstearyl alcohol.........1.................... Water......5 Cremophor A 25 [1] ....8 III...6................... 4.............................................. Physical stability No change of appearance or crystallization were observed during 6 weeks at 45 °C. Formulation I..... Properties White cream....7.........0 Cremophor A 6 [1] ........................ 5.. Add the water II to the obtained solution I with rigorous stirring.....0 Parabene(s)...........................

..6.......60........ Formulation I....................9 Water .........................5 Water..... Properties Clear...........0 Triethanolamine ..5 %) 1........24... II.............. colourless gel....... Hydrocortisone acetate............................7................... 3..6..0 Carbopol 940 (Goodrich) ............................6 Ethanol 96 % ..........5 Cremophor RH 40 [1] ..............7 Formulations of semi-solid drugs (Lab scale) Hydrocortisone Ethanolic Gel (0..... BASF Fine Chemicals Generic Drug Formulations 1998 .5 g g g g g g g 2.0......................0...........................0............. Manufacturing Prepare solution II and mix slowly with solution I..........

..........7 Formulations of semi-solid drugs (Lab scale) Ibuprofen Gel-Cream (5 %) 1............44 IV........................................ Die Creme wird bis zum Erkalten gerührt und das verdampfte Wasser ersetzt............................25 Wasser.......5 Propylene glycol Pharma [1] ........... Water..... Ibuprofen (Knoll-Boots) ............. Formulation I........... Manufacturing Prepare solution I and coll to about 8°C.... Die Creme kann mit 0.......12 Isopropanol ........ Maintain cool until the air bubbles escaped......................50 Teile Teile Teile Teile Teile In das auf dem Wasserbad auf etwa 70 °C erwärmte Gemisch von Polysorbat 60............1 Prozent Sorbinsäure konserviert werden......................................6..........5 Cetylstearylalkohol ... Cetylstearylalkohol und Weißem Vaselin wird die auf gleiche Temperatur erwärmte Mischung der übrigen Bestandteile in Anteilen eingearbeitet............12 III............................. BASF Fine Chemicals Generic Drug Formulations 1998 . Das für die Herstellung verwendete Wasser soll vor Gebrauch frisch aufgekocht werden.. Dissolve II and add III and IV............12 II...................10 Glycerol 85% ..15 g g g g g g 2...... *Nichtionische hydrophile Creme (DAB 1996) Polysorbat 60 .....10 Weißes Vaselin.......................... Nonionic hydrophilic Cream (DAB 1996)*............ Lutrol F 127 [1] .......................................................

. 2... Water ... Remark The function of isopropyl myristate is the reduction of the adhesive properties of Lutrol F 127.... BASF Fine Chemicals Generic Drug Formulations 1998 .. The gel of formulation No................ s.............. Isopropyl myristate ........... Properties of the gel A colourles clear gel was obtained.................... 1...43 g 5g 10 g 10 g 15 g 1g q.q....... Manufacturing Heat solution I to 70 – 80 °C..... 3.. 2 is less adhesive than formulation No...................................... 1 No....22 g III.....................7 Formulations of semi-solid drugs (Lab scale) Ibuprofen Gels (5 %) 1................ 59 g I............ 2 Ibuprofen (Knoll-Boots)..... Lutrol F 127 [1]........ 4................ s....5 g Ethanol 96 % ...........20 g II..........6....................................... dissolve II..10 g Propylene glycol Pharma [1]........................ add III and cool.....– Preservative ......... Formulations No..........................

............ Formulation I...................... Ibuprofen (Knoll-Boots) .........5...............2 g Cremophor RH 40 [1] ..............q.78 g 2...... Manufacturing Suspend Ibuprofen in the hot Cremophor RH 40 (about 60 °C) and add slowly the hot solution II...............8 Liquid Formulations (Lab scale) Ibuprofen Solution (2 %) 1.. BASF Fine Chemicals Generic Drug Formulations 1998 ... Physical stability The solution remained clear more than one week at 6 °C..................20 g Preservatives.. Water..... II............... 3............................. s........

8 Liquid Formulations (Lab scale) Ibuprofen Suspension (4 % = 400 mg/10 ml)...white Aspect ................. I 1.......................... Suspension properties Color .............................94 % (after 4 weeks) Redispersibility.................. Manufacturing Dissolve sucrose.........................100 % (after 1 day) Rel..............5................very easy (after 4 weeks) BASF Fine Chemicals Generic Drug Formulations 1998 ....ad 100 ml 2. 3........ Kollidon 90 F and sodium citrate in about 40 ml of water.........................................................Homogeneous Viscosity...................8 g Kollidon 90 F [1] ....2 g Water............ suspend Kollidon CL-M and ibuprofen in this solution by stirring and add the rest of water......... sediment volume ........... sediment volume ..........................................................................................................25 g Kollidon CL-M [1] ................................4 g Sucrose ................................ Formulation Ibuprofen (Knoll-Boots) .............................................................low Rel.......2 g Sodium citrate...

Relative sediment volume. 4 weeks [%] 4. Influence of the amount of Kollidon CL-M on the sedimentation 100 90 80 70 60 50 40 30 20 10 0 2 4 BASF Fine Chemicals Generic Drug Formulations 1998 6 Kollidon CL-M [%] 8 10 .

.10......... Ibuprofen (Knoll-Boots) .0 g Cremophor RH 40 [1] ..................... Formulation I................ II 1... II......... The viscosity is low.... 3.............. Water.0 g Lutrol F 68 [1]....5................8 Liquid Formulations (Lab scale) Ibuprofen Suspension (4 % = 400 mg/10 ml)....................................................... Add the solution II slowly to the ibuprofeneCremophor RH 40 mixture I whilst stirring........5...0 g Preservative ....q...s........................4.... BASF Fine Chemicals Generic Drug Formulations 1998 ....... Properties of the suspension The redispersibility of the suspension is very easy after 14 days at room temperature..... Manufacturing Dissolve Lutrol F 68 and the preservative in water II and ibuprofene in Cremophor RH 40 (I).........81 g 2.

........................... 1 No..........................................18 g Magnesium stearate [2] .......................99 % 752 mg 16 mm 112 N 2 – 3 min 0...........................................................................27 g Ludipress [1] ..................3 % Dissolution..................6 g Avicel PH 102 [5] ......... 3.......< 1 min Friability ..................................... add the other components and press with low compression force.– Kollidon CL [1] .............................................................9 Tablet formulations (Lab Scale) Ibuprofen Tablets (400 mg)...... 1: Mix ibuprofen with Aerosil 200........................12 mm Hardness ............. 2 Ibuprofen 50 (Knoll-Boots) .................... Manufacturing (Direct compression) No...........................3 g – 400 g 4g – – 342 g 8g 8g 2................... mix with the other components and press with medium compression force....400 g Ibuprofen (Francis) .. 1 No................ 2: Pass ibuprofen and magnesium stearate through a 200 µm sieve....................... DC 1...93 N Disintegration.98 % 15 min ..........79 g Kollidon VA 64 [1]........................... No....... 10 min ........2........ Formulations No...................................................533 mg Diameter .................4 % 82 % 91% BASF Fine Chemicals Generic Drug Formulations 1998 ..................0........................................ 2 Weight ..........................– Aerosil 200 [4]................... Tablet properties No.

2 (20–25ºC) 6 Months Hardness Disintegration Friability Dissolution.4 % – 91% 120 N – 0.4.2 % 89 % 88 % . Physical stability of formulation No. 10 min 20 min BASF Fine Chemicals Generic Drug Formulations 1998 – – – 85 % 87 % 8 Months 12 Months 121 N 2 – 3 min 0.

.............................90 N Disintegration ...... Kollidon 30 [1] ...0......s................16 g Aerosil 200 [4].............. 1 (3 months.............81% BASF Fine Chemicals Generic Drug Formulations 1998 .......... pass through a 0............................... add III and press with low compression force................ 3.......... 8g 2............ 400 g 38 g I............8 g – 289 g 15 g q.......................12 mm Form .........4 % Dissolution (30 min) ........... Tablet properties No.......s.2 min Friability ..................2.....................................8 g Magnesium stearate [2] ........3 % – 4......9 Tablet formulations (Lab Scale) Ibuprofen Tablets (400 mg)...... Formulations No...............q.....– II............................. 1 No............. Ibuprofen (Knoll-Boots) .......... Manufacturing (Wet granulation) Granulate mannitol or dicalcium-phosphate with solution II.....12 g Water ........................................... WG 1..........774 mg Diameter ................... 1 No........................................85 % 741 mg 12 mm biplanar 177 N 1-2 min 0...... Dissolution stability of formulation No.................................................................... 2 Mannitol ................. III..................400 g Kollidon CL [1] ..........................................8 mm sieve.................. 20–25 ºC) Dissolution (30 min)... 2 Weight .......................biplanar Hardness ........................330 g Dicalcium phosphate [9] ..............................................................................

.................. Avicel PH 102 [5] .......... 10 min...........................................................................11 min Friability....2............290 mg Diameter ..... 3.......................8 mm sieve.........................................2 g g g g g g g g g g 2.......1..............0 Croscarmelose [5] ..............20....................................... Manufacturing (Wet granulation) Granulate mixture I with solution II............................. Tablet properties Weight ..2......3.............. Ibuprofen .0...95 % 20 min.52.0 Avicel PH 101 [5] ......................... dry...................0 Potato starch [3] ....................0 Aerosil 200 [4] ................0 Water.0 III...........................................2 % Dissolution.........0 II..10 mm Form ........................................................................150..18....... BASF Fine Chemicals Generic Drug Formulations 1998 ..............................................20..............100 % 4............... pass through a 0............... Formulation I....7 Magnesium stearate [2]................biplanar Hardness .0........................ mix with III and press with medium compression force (17 kN)........................... Kollidon 30 [1] ................0 Lactose monohydrate [8] ..........108 N Disintegration..........9 Tablet formulations (Lab Scale) Ibuprofen Tablets for Children (150 mg) 1...76........... Remark Croscarmelose could be substituted by Kollidon CL.................

......................... Physical stability (4 weeks.............. 3...................6....7 Formulations of semi-solid drugs (Lab scale) Indomethacin Gel (1%)................ I 1. Formulation Indomethacin .. 4............. BASF Fine Chemicals Generic Drug Formulations 1998 . add slowly the water (60 – 70°C) stirring well the mixture and dissolve Lutrol F 127.74 g g g g 2... Manufacturing Dissolve indomethacin in Cremophor RH 40 at 60 – 70°C.. Cool to room temperature........... 40 °C) No change of appearance.15 Water..................................1 Cremophor RH 40 [1]....10 Lutrol F 127 [1] .................................. Properties of the gel A clear soft gel was obtained.....

............6........ 2: No change during 12 weeks at 40 °C........................20............ 1: No change during 1 year at room temperature..................... Formulation No... dissolve II well stirring about 30 minutes. Manufacturing Heat solution I to about 70°C.....– Lutrol E 400 [1] . Lutrol F 127 [1].. Water ...... 3.... 2 1.. 1 I.......38................0 g g g g g g 2...............0 39.....0 g II....................... mix with III and cool...0 g Ethanol 96 %..0 – 15..................0 g No........7 Formulations of semi-solid drugs (Lab scale) Indomethacin Gel (1%).... Physical stability Formulation No..... II 1.0 22.21..0 g III... BASF Fine Chemicals Generic Drug Formulations 1998 ................ It forms a clear yellow gel...... Indomethacin .....1...... 23 °C and 6 °C.......0 23....................20.......0 g Propylene glycol Pharma [1] ........... Formulations No..........

with linear plots of the 1st order rate constant vs.: Acta Pharm. No.. 2. pH in both Pluronic and aqueous solutions. Chemical stability Lutrol F 127 (= Pluronic® F 127) stabilizes indomethacin against hydrolisis as shown in the following publication summary: Hydrolysis of Indomethacin in Pluronic F 127 Gels Tomida H.) were considerably slower in Pluronic F 127 (BASF) gels than in buffer alone. The degradation of indomethacin followed 1st order kinetics. Kuwada N. Kiryu S. 25. the rates of hydrolysis of indomethacin (Sigma-Chem..4. 87 – 96 (1988) „In drug stability studies. allowing prediction of the time required for degradation of indomethacin.“ BASF Fine Chemicals Generic Drug Formulations 1998 . Suec.

... Formulation Indomethacin . Manufacturing Mix the components for about 10 min and fill in hard gelatin capsules to obtain 160 mg indomethacin in each capsule.q.............. 2.................s............ Indomethacin dissolved [%] 3.........320 g Aerosil 200 [4] ...................... dry syrups and Iyophylisates (Lab scale) Indomethacin Powder for Hard Gelatin Capsules (160 mg) 1.............4 Formulation of granules..... Dissolution 100 80 with Kollidon CL 60 40 20 without Kollidon CL 0 0 15 30 45 60 75 Minutes 90 105 120 BASF Fine Chemicals Generic Drug Formulations 1998 ......4............160 g Kollidon CL [1].....................

........................................................ Properties of the suppositories Weight: ........................ Formulation I........3......5...8............ Indomethacin ..... Manufacturing Prepare solution II.........................3 mg Water..........14................................ mix with the melted mixture I and fill into the moulds of suppositories.........................3 mg Lutrol E 4000 [1] ......................0 g Lutrol E 6000 [1] ...........................141..... II...............................6....slightly yellowish BASF Fine Chemicals Generic Drug Formulations 1998 . 3.0 g EDTA .0 g Butylhydroxytoluene ..............1....6 g Colour:........16..........0 g 2....7 Formulations of semi-solid drugs (Lab scale) Indomethacin Suppositories (50 mg) 1................

................. Formulation Indomethacin ................ Tablet properties Weight ...................9 Tablet formulations (Lab Scale) Indomethacin Tablets (50 mg)...................................................2 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................................................3 min Friability............ Manufacturing (Direct compression) Mix all components.......303 mg Diameter ................... 3.......................................biplanar Hardness ...........................................227 Kollidon CL [1] .......176 N Disintegration ................20 Magnesium stearate [2] .8 mm sieve and press with medium compression force................8 mm Form ............................................... DC 1........3 g g g g 2..........2............................................... pass through a 0.......0..........50 Ludipress [1] ...............

....................... Formulation I...... Indomethacin .............10 Water................................72 N Disintegration ..1% BASF Fine Chemicals Generic Drug Formulations 1998 .................. add III and press with low compression force.............................................1% 0.................. Kollidon 30 [1] ..........................12 Aerosil 200 [4] ........................................ Kollidon CL [1].......................88 % 4....2 g g g g g g g 2.......<1 min Friability ...................... 3..9 Tablet formulations (Lab Scale) Indomethacin Tablets (50 mg).. 10 min. pass through a 0..... Physical stability (20–25°C) Storage time Hardness Disintegration Friability 6 Months 12 Months 70 N 55 N <1 min <1 min 0..........................12 mm Form .............................0.................2.....372 mg Diameter ..................................................... Manufacturing (Wet granulation) Granulate mixture I with solution II.............................................8 mm sieve..........1% Dissolution...................................... WG 1.......................................biplanar Hardness.............. Tablet properties Weight ...............2 Magnesium stearate [2] ..................75 % 20 min .....50 Lactose monohydrate [8] ..............................30 III...............300 II................

..............................500 mg Diameter .....397 g Magnesium stearate [2] . Manufacturing (Direct compression) Mix all components.......5 min Friability.......................................9 Tablet formulations (Lab Scale) Indomethacin Tablets (100 mg) 1..........61 N Disintegration .......................8 mm sieve and press with low compression force.........2..................................................12 mm Form ..biplanar Hardness......100 g Ludipress [1] ............................. pass through a 0......... Formulation Indomethacin ........................3 g 2..............4 % BASF Fine Chemicals Generic Drug Formulations 1998 .......... 3............................................................................................................ Tablet properties Weight ....................0...................

0 % BASF Fine Chemicals Generic Drug Formulations 1998 ................55 N Disintegration ..................9 Tablet formulations (Lab Scale) Inosin Tablet Cores (200 mg) 1....................................................... dry.......................... Formulation I.................60 ml III........................................................................ Russia) ...9 mm Form .............8 mm sieve................... pass through a 0..................... 3...........200 g Lactose monohydrate [8] ......3 – 4 min Friability ....... Inosin (Ribaxin......... add the components III and press with low compression force.....................270 mg Diameter ................................................biconvex Hardness...........................3 g 2.. Isopropanol .........10 g Magnesium stearate [2] ..............51 g Kollidon 90 F [1] ............................ Tablets properties Weight ............................................ Kollidon CL [1]... Manufacturing (Wet granulation) Granulate mixture I with the solvent II............2...........6 g II......

.............................................1 g Kollidon 30 [1] ...........................< 1 min Friability .................152. pass through a 0............................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...4 g Kollidon CL [1] ...................8 mm Form ............................5 g Lactose monohydrate [8] .........9 Tablet formulations (Lab Scale) Isosorbide Dinitrate Tablets (5 mg) 1....45 N Disintegration ........................5..0 g Magnesium stearate [2]............. Manufacturing (Direct compression) Mix all components...1...............9..................................................... Formulation Isosorbide dinitrate + Lactose (4+6).184 mg Diameter ........ Tablet properties Weight ..........biplanar Hardness.............................2...........12...........................0 g 2..................0..8 mm sieve and press with low compression force......... 3.........................

...150 mg Diameter ...................8 mm sieve.........8 mm Form .............................................124 g Magnesium stearate [2] .............................................. mix intensively and press with low compression force (10 kN)....... 3..........................................65 N Disintegration .........about 1 min Friability............................................1 g 2........2....................................................... Formulation Khellin ..................... Manufacturing (Direct compression) Pass all components through a 0.................25 g Ludipress [1] ................0.....25 % BASF Fine Chemicals Generic Drug Formulations 1998 ................................... Tablet properties Weight .................biplanar Hardness...................9 Tablet formulations (Lab Scale) Khellin Tablets (25 mg) 1.

.......................................80 N Disintegration ................. 3..0........................................................ pass through a 0...............9 Tablet formulations (Lab Scale) Levamisole Tablets (150 mg) 1..............300 g Magnesium stearate [2] .................... Tablet properties Weight ....3 – 4 min Friability......2..............................................12 mm Form .....................4 g 2......2 % BASF Fine Chemicals Generic Drug Formulations 1998 .... Manufacturing (Direct compression) Mix all components.............................................................8 mm sieve and press with low compression force.................................458 mg Diameter ..150 g Ludipress [1] ........biplanar Hardness................................... Formulation Levamisole hydrochloride ....

....2..not controlled 101 mg 6 mm biplanar 45 N 4 min < 0........................05 mg) 1......... Remarks If the content uniformity of formulation No....................... Levothyroxine sodium ................................ anhydrous...00 g Ludipress [1] ......99..................... Manufacturing (Direct compression) Prepare premix I.. II..................1 – 2 min Friability................ The effectiveness was not controlled in this formulation............1..8 mm sieve.biplanar Hardness ........................ 1 I.......05 10............................. add II and pass the mixture through a 0................... 2 0... 2 is the stabilization of the active ingredient..... The function of citric acid in formulation No...6 mm Form ............................. 2 Weight ...................................0..................1% Content uniformity .05 g Citric acid..........1% 4...........00 1.. 1 No......... Tablet properties No...52 N Disintegration............................00 89..0..........9 Tablet formulations (Lab Scale) Levothyroxine Tablets (0.......................................– Magnesium stearate .....00 g No...........103 mg Diameter .00 g g g g 2............. 3.... 1 does not meet the requirements it would be recommended to add a small part of Ludipress (= part II) to the premix I....... BASF Fine Chemicals Generic Drug Formulations 1998 ......... Mix and press with low compression force........ Formulations No..............

........................... 20–25°C) No change was observed.....56 Propylene glycol Pharma [1] ............ Properties of the gel A clear colourless gel was obtained........ BASF Fine Chemicals Generic Drug Formulations 1998 .. Physical stability (3 months.......20 Lutrol F 127 [1] ...................... Formulation I.......... 4.. 3........... Maintain the temperature until the air bubbles escaped..... Lidocain hydrochloride..2 Water....6.. Manufacturing Prepare solution I at room temperature..22 g g g g 2........ II........................... heat to 70 °C or cool to 6 °C and add slowly II to the well stirred solution until it is dissolved.....7 Formulations of semi-solid drugs (Lab scale) Lidocain Gel (2 %) 1.......

Formulation I....5 Water.................................................. 20–25°C) No change was observed...7 Formulations of semi-solid drugs (Lab scale) Lidocain Gel-Cream (5 %) 1......................20 g g g g g 2................ 3.......... Physical stability (3 months.................. Liquid paraffin ..6..............10 III..15 II......... Maintain cool until the air bubbles escaped......... Manufacturing Prepare solution I at room temperature and mix with II........... Lutrol F 127 [1] ... BASF Fine Chemicals Generic Drug Formulations 1998 ........ Lidocain hydrochloride....... Heat to 70 °C or cool to 6 °C and add slowly III to the well stirred solution until it is dissolved....................50 Propylene glycol Pharma [1] ..

..................10 g Ludipress [1] .......................8 mm sieve..biplanar Hardness..................................... Tablet properties Weight .....................0......2 % BASF Fine Chemicals Generic Drug Formulations 1998 .........152 mg Diameter ........................................8 mm Form ............................1 g 2..................................94 N Disintegration................... Manufacturing (Direct compression) Pass all components through a 0.................................. 3................................. mix intensively and press with low compactation force (10 kN)...........................................2 – 3 min Friability........2.................9 Tablet formulations (Lab Scale) Lisinopril Tablets (10 mg) 1....................... Formulation Lisinopril ......................139 g Magnesium stearate [2] .....

3....... dry.....50 II.................................. Kollidon 90 F [1] .................................................................. Tablet properties Weight..........1% Taste .3 g g g g g g g g g g 2........................ mix with III and press with low compression force..............2.............................................................9 Tablet formulations (Lab Scale) Magaldrate Chewable Tablets (500 mg) 1............................................................................................72 N Disintegration (water) ...6 Saccharin sodium..............400 Orange flavour (FDO) ........ pass through a 0......60 min Friability ......................................................biplanar Hardness.........................................500 Lactose monohydrate [8] ........................1 Water ............16 mm Form .20 Banana flavour (FDO).........< 0..........6 Cocos flavour (FDO) ............................................ Aerosil 200 [4] ............................. Manufacturing (Wet granulation) Granulate mixture I with solution II..........180 III.....good BASF Fine Chemicals Generic Drug Formulations 1998 ....................................1000 mg Diameter ....................5 Magnesium stearate [2] .........8 mm sieve................................... Magaldrate USP .. Formulation I.................................

......................................................................................700 Lactose monohydrate [8] .........................................435 Kollidon 90 F [1] ..................1. 3..1% BASF Fine Chemicals Generic Drug Formulations 1998 .... Formulation Magaldrate.....................25 sec Friability ...........................200 mg Diameter ......9 Tablet formulations (Lab Scale) Magaldrate Dispersible Tablets (700 mg) 1...........................................................5 g g g g g 2.....10 Kollidon CL [1] .. mix and press with low compression force (4 – 6 kN)........biplanar Hardness ...........................125 N Disintegration (water)......... Tablet properties Weight ....................16 mm Form ....0.......8 mm sieve........................................................50 Magnesium stearate [2] .............................. Manufacturing (Direct compression) Pass all components through a 0...........................2.......

.0..2 g Water ...........10..................0 g Coconut flavour .about 70 ml 2..........1...... Manufacturing Granulate mixture I with solution II and pass through a 0........................................ Administration • Instant granules in sachets: Suspend 2 g (= 1 sachet) in a glass of water (= 800 mg Magaldrate) • Dry syrup: Fill the flask with drinking water until the mark of 100 ml and shake well... 3.......4.......0 g Sorbitol.0 g Orange flavour ...............0 g Banana flavour .............. 10 ml of the suspension correspond to 800 mg Magaldrate...0 g Saccharine sodium ....................................................................4 Formulation of granules..100.................. Fill 2 g in sachets or 20 g in a 100 ml flask................. Magaldrate USP ......1......0 g Kollidon CL-M [1]......................8 mm sieve to obtain free-flowing granules............ dry syrups and Iyophylisates (Lab scale) Magaldrate Instant Powder or Dry Syrup (800 mg) 1......10..50.. II..............0 g Kollidon 90 F [1] ......80.......... BASF Fine Chemicals Generic Drug Formulations 1998 ...... Formulation I....... crystalline [10] ...........

10....1..5...........8 Liquid Formulations (Lab scale) Magaldrate Suspension (10 %) 1........... – Very easy to redisperse by shaking after the storage of more than 2 weeks... Water..................0 g Kollidon CL-M [1] ..........................0...............q..........0..........08 g Saccharine sodium .................05 g Banana flavour ........ BASF Fine Chemicals Generic Drug Formulations 1998 ........... – pH value about 9...ad 100 ml 2.......... 3................................................ Properties of the suspension – White homogeneous suspension practically without sedimentation during 24 hours....... Manufacturing Dissolve or suspend all the solids in water under aseptic conditions........8...0.......................0 g Coconut flavour ..................02 g Preservatives.....................................2............ Formulation Magaldrate USP ......................................s.....0 g Kollidon 90 F [1] .............0 g Orange flavour ..

Number of shakings needed to homogenize 4. Influence of the Kollidon 90 F concentration on the redispersibility after 7 days 25 20 15 10 5 0 0 2 1 Kollidon 90 F [%] BASF Fine Chemicals Generic Drug Formulations 1998 3 .

..................238 g Magnesium stearate [2] ..................................< 0............................4 g 2.............................168 N Disintegration .............499 mg Diameter .......262 g Ludipress [1] .......2.....................1% BASF Fine Chemicals Generic Drug Formulations 1998 .8 mm sieve and press with medium compression force.........................biplanar Hardness ............ Tablet properties Weight ..... Formulation Magnesium carbonate USP..........................................9 Tablet formulations (Lab Scale) Magnesium Carbonate Tablets (260 mg) 1............................ pass through a 0............ Manufacturing (Direct compression) Mix all components............................................1 min Friability ..........................................................12 mm Form . 3.....

.............................................biplanar Hardness.........2 min Friability...............73 N Disintegration ......196 g Magnesium stearate [2] .. Manufacturing (Direct compression) Mix all components.............. Tablet properties Weight ..................... Formulation Mebendazol .........................................8 mm sieve and press with low compression force..................... pass through a 0...2........................................9 Tablet formulations (Lab Scale) Mebendazol Tablets (100 mg) 1........................................................0.........................12 mm Form .........4 g 2...............................................5 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........294 mg Diameter ............................................... 3...100 g Ludipress [1] ...

......2 Lutrol F 127 [1]........................ When the Lutrol F 127 is completely dissolved suspend Mebendazole in the solution............. Properties of the suspension After one day of storage at room temperature no sedimentation could be observed.............................. Manufacturing Dissolve the parabens in water at 80 °C......02 Water ....0..... BASF Fine Chemicals Generic Drug Formulations 1998 ................. After cooling to room temperature add Lutrol F 127 whilst stirring.............5.........8 Liquid Formulations (Lab scale) Mebendazole Suspension (2 % = 200 mg/10 ml) 1..........18 Propylparaben.................... After some weeks of storage at room temperature some sedimentation occurred but the redispersibility was very easy..............3 Methylparaben..........0.... Formulation Mebendazole .......... 3........ad 100 g g g g g 2............................

............s...........0.............404 mg Diameter ...........................5 g 2.........................................q.... sieve.85 g Magnesium stearate [2] .9 Tablet formulations (Lab Scale) Mefenamic Acid Tablets (250 mg) 1. Manufacturing (Wet granulation) Granulate mixture I with solution II.......... Tablet properties Weight ...........................................biplanar Hardness..........................40 g II........................ 3............ Formulation I.......................................2 min Friability................................12 g Avicel PH 101 [5] ............................................ dry.........2............... III......................................................8 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................70 N Disintegration ...............5 g Isopropanol ..... Kollidon CL [1]................................. add mixture III and press with medium compression force..250 g Corn starch [3] .....................................12 mm Form .......... Kollidon 90 F [1] .................... Mefenamic acid ...................

..................................13 Kollidon CL [1] .........................30 Avicel PH 101 [5] ............................................... DC 1...................................................................................................................551 mg Diameter ..................1 g g g g g g g g 2....... 3.........1 Calcium arachinate [2] ................12 mm Form .....................................76 Kollidon VA 64 [1] . Tablet properties Weight .. Formulation Meprobamate....2............................9 % BASF Fine Chemicals Generic Drug Formulations 1998 .........................................8 mm sieve.............................0..............................................< 1 min Friability..................biplanar Hardness..........................9 Tablet formulations (Lab Scale) Meprobamate + Phenobarbital Tablets (400 mg + 30 mg)............................. mix and press with low compression force..21 Talc [10] ........400 Phenobarbital.........................87 N Disintegration ................................ Manufacturing (Direct compression) Pass all components through a 0..................................8 Aerosil 200 [4] ..

...................................< 1 min Friability..................................................................... WG 1........................131 N Disintegration .................................................2.......... pass through a 0......................1 g Calcium arachinate [2] .................................................................50 g Avicel PH 101 [5] .................s............................biplanar Hardness .... mix with III and press with low compression force..........559 mg Diameter ... Kollidon CL [1] ..............8 g Aerosil 200 [4] .................................................... III...........12 mm Form .........................8 mm sieve... Manufacturing (Wet granulation) Granulate mixture I with solution II...............................................0..400 g Phenobarbital........................ dry.......4 % BASF Fine Chemicals Generic Drug Formulations 1998 ........ 3......... Formulation I........21 g Corn starch [3] ..30 g II.............................. Kollidon VA 64 [1] ..........................13 g Isopropanol .................... Meprobamate.........q............. Tablet properties Weight ..................................9 Tablet formulations (Lab Scale) Meprobamate + Phenobarbital Tablets (400 mg + 30 mg).......60 g Talc [10] ............1 g 2...............................

.................................................................................................. Formulation Meprobamate..................................400 Avicel PH 101 [5] ..........90 N Disintegration .3 g g g g g g g 2...12 mm Form .6 % BASF Fine Chemicals Generic Drug Formulations 1998 ......80 Corn starch [3] ..............20 Kollidon CL [1] ................. pass through a 0........ 3................7 Magnesium stearate [2] ..............................0.......................9 Tablet formulations (Lab Scale) Meprobamate Tablets (400 mg)................ DC 1.....................30 Kollidon VA 64 [1] .........560 mg Diameter ........< 10 min Friability .................................................................................... Manufacturing (Direct compression) Mix all components.......................8 mm sieve and press with high compression force (20 KN)..............................2.........biplanar Hardness...................................... Tablet properties Weight ...............................................................................20 Talc [10] .....

....................0 g Kollidon VA 64 [1]..............0 g Corn starch [3] .. 3........ Talc [10] ..................................................– Lutrol E 400 [1] ......................... 1 No........ Kollidon 25 [1] ........................................................0 g II....0..0 g Aerosil 200 [4] .1% BASF Fine Chemicals Generic Drug Formulations 1998 .....................2.................s................................5 % 500 mg 12 mm biplanar 88 N 3 – 4 min < 0........9 Tablet formulations (Lab Scale) Meprobamate Tablets (400 mg)..............15...5 g Isopropanol........................................95 N Disintegration .............. 2 Meprobamate...3 g 400........ 2......... add III and press.................400......................... pass through a 0...5 min Friability ................................2 g Calcium arachinate [2] .520 mg Diameter . Tablet properties No...... Formulations No.............8 mm sieve...... 2...................... 1 No..3 g I......................0.0 g – q......0 g 100...0 g – 15...................100........ III................................................................ WG 1....0.s..............q.................. Manufacturing (Wet granulation) Granulate the mixture I with solution II.....................biplanar Hardness .........0 g 0..........2....................................2 g 0..... 2 Weight ..........................4..............12 mm Form .

........................................................5 min Friability ...................................10 g Aerosil 200 [4]..........................12 mm Form .................................. 2 Weight ..................0....... 1 No................................9 Tablet formulations (Lab Scale) Metamizol Tablets (500 mg) 1....100 g Avicel PH 101 [5]..– 500 g – 100 g 15 g 25 g – 1g 8g 1g 2...10 g Magnesium stearate [2].........................625 mg Diameter .......................................................................................................................................... pass through a 0.....................................5 g Talc [10] .......................................500 g (= Dipyrone) Ludipress [1] ..............– Calcium arachinate [2] ....................................... Manufacturing (Direct compression) Mix all components.......... 1 No....– Kollidon CL [1] ............ Tablet properties No..................................................5 mm sieve and press with low compression force...........................120 N Disintegration ................... 2 Metamizol sodium ...............................3 % 654 mg 12 mm biplanar 62 N 2 min 1% BASF Fine Chemicals Generic Drug Formulations 1998 .....2.................................– Kollidon 30 [1]....................biplanar Hardness............ Formulations No............... 3........

...3 % 4......................> 200 N Disintegration ...............90 g III..........0.15 g II...........................650 mg Diameter ........8 mm sieve and press with medium compression force... pass through a 0.500 g Dicalcium phosphate [9]......................12 mm Form .................................................. Formulation I.......2.. Kollidon CL [1] ............. mix with III... Metformin hydrochloride ......6 min Friability.................................................................5 g Polyethylene glycol 6000.............................................. powder [6] ............biplanar Hardness .......... BASF Fine Chemicals Generic Drug Formulations 1998 ............................................. Kollidon 90 F [1] .................................100 g Kollidon 90 F [1] .............................................. 3... Manufacturing (Wet granulation) Granulate the mixture I with solution II..8 g Isopropanol.... Remark Due to the high hardness the amount of Kollidon 90 F could be reduced..............................9 Tablet formulations (Lab Scale) Metformin Tablets (500 mg) 1.................. Tablet properties Weight .................15 g 2.............

..............55 N Disintegration...........8 mm sieve and press with low compression force....................................................................... 3..............100 g Ludipress [1] .........9 Tablet formulations (Lab Scale) Methyl Cysteine Tablets (100 mg) 1..........2 – 3 min Friability............2............................3 % 4.................. Formulation Methyl cysteine hydrochloride ................................. pass through a 0..0........................................................................................ Tablet properties Weight .8 mm Form ..................................................3 mg Menthol ............2 % BASF Fine Chemicals Generic Drug Formulations 1998 .... Physical stability (12 months..307 mg Diameter ..............................................biplanar Hardness................................................ 20–25 ºC) Weight ...307 mg Hardness....2 – 3 min Friability.......200 g Magnesium stearate [2]................0....................4 mg 2.......85 N Disintegration...................... Manufacturing (Direct compression) Mix all components.............................................................................

......................................... 3............................................19 g g g g g g g 2........ Formulation I.......... 4...............6 Propylene glycol Pharma [1] ......................... The clear gel can be diluted with water. Methyl salicylate .............20 Cremophor RH 40 [1] ..............5 Lutrol E 400 [1].....7 Formulations of semi-solid drugs (Lab scale) Methyl Salicylate + Menthol Gel (11% + 5 %) 1...............11 Menthol ..32 III.. Remark Reducing the concentration of the active ingredients the amount of Lutrol F 127 could be reduced too and the consistency of the gel will be normal... Manufacturing Dissolve II in solution I and mix with III................... Water..................................6.......7 II.................. Lutrol F 127 [1] .......... BASF Fine Chemicals Generic Drug Formulations 1998 ............. Properties of the gel Due to the high concentration of the active ingredients and of Lutrol F 127 the consistency of the colourless clear gel is extremely hard.......

......0 g Ludipress [1] ...............................5 g Magnesium stearate [2]....1% Dissolution (15 min) .. Formulation Metoclopramide hydrochloride .......3 min Friability ......0...........3 min Friability .........................100 % 4......................5 g 2..................1% Dissolution (15 min) .....................35 N Disintegration (gastric juice) .............100 mg Hardness....biplanar Hardness................... Manufacturing (Direct compression) Mix all components.........9 Tablet formulations (Lab Scale) Metoclopramide Tablets (10 mg) 1....................... 20–25 ºC) Weight .......................... pass through a 0............................0......6 mm Form ....................................................................100 % BASF Fine Chemicals Generic Drug Formulations 1998 ... Tablet properties Weight ..............8 mm sieve and press with medium compression force..................................89................................. Physical stability (18 months.......0......................... 3..........................100 mg Diameter .....2..................................10..............................35 N Disintegration (gastric juice) ....................................................

............16 mm Form .....9 Tablet formulations (Lab Scale) Metronidazole Effervescent Vaginal Tablets (500 mg) 1......... Formulation I.................................................................. pass through a 0...150 ml III..........10 g Isopropanol ......................... Manufacturing (Wet granulation) Granulate I with solution II.... Tablet properties Weight.................................................................. Tartaric acid..................................500 g Polyethylene glycol 6000...... powder [6].600 g Kollidon 30 [1] .......................................................8 % BASF Fine Chemicals Generic Drug Formulations 1998 ..............................30 g II.....................4 min Friability...... Kollidon 30 [1] ..........2..... mix with III and press...........................................1700 mg Diameter ......... crystalline............ Metronidazole ...............8 mm sieve...........................50 g 2...............................500 g Sodium bicarbonate .............113 N Disintegration ..... 3...1.............biplanar Hardness ...

.............2 to 0.............. 3............... Properties of the solution A clear solution was obtained.4 with III and heat until metronidazol is dissolved................... Remark To prevent of discolouration of Kollidon in the solution during storage 0..........0 g Lutrol E 400 [1]....... adjust pH 4..q...........8 Liquid Formulations (Lab scale) Metronidazol Injectable Solution (500 mg/10 ml) 1.. 4........... II...........5.....0 g Propylene glycol Pharma [1] ...........25. Hydrochloric acid 0.......1 N ...25......... Metronidazol .........0 g Kollidon 12 PF [1] ... Formulation I. Manufacturing Suspend I in the solution II.25..........5...20.. It can be diluted with water without precipitation. 2....5 % of cysteine could be added as antioxidant.............................0 g III.0 g Water for injectables ...s.... BASF Fine Chemicals Generic Drug Formulations 1998 .

.9 Tablet formulations (Lab Scale) Metronidazole Tablet Cores (400 mg) 1.........................1% BASF Fine Chemicals Generic Drug Formulations 1998 ..................15 g Aerosil 200 [4] .400 g Avicel PH 102 [5] ..........................................2......< 0............................ Formulation Metronidazole .......150 g Kollidon VA 64 [1] .....8 mm sieve and press with high compression force (25 – 30 kN)........................................... pass through a 0...........................................................87 N Disintegration.biconvex Hardness................50 g 2.......12 mm Form . powder [6].................................................................... 3.................................................................645 mg Diameter ...........5 g Polyethylene glycol 6000.............................. Manufacturing (Direct compression) Mix all components................1 – 2 min Friability ......... Tablet properties Weight ..............25 g Kollidon CL [1].................................

....... 3..... Tablet properties Weight ............................................... pass through a 0...................................5 Magnesium stearate [2] ...................................2....133 N Disintegration....8 mm sieve and press with high compression force (25 – 30 kN).........................................200 Kollidon 30 [1] ...10 Aerosil 200 [4] ................................................................................................................................ Formulation Metronidazole ...........................................200 Avicel PH 101 [5] ...........< 0.......................1 – 2 min Friability ....9 Tablet formulations (Lab Scale) Metronidazole Tablets (200 mg) 1............6 Kollidon CL [1]......................... Manufacturing (Direct compression) Mix all components............1% BASF Fine Chemicals Generic Drug Formulations 1998 ..........................426 mg Diameter .................................12 mm Form ...................biplanar Hardness ..5 g g g g g g 2.............

............ Metronidazole...........20 Talc [10] .16 mm Form ........................................................10 Ethanol 96 %....8 mm sieve..500 Sorbitol......9 Tablet formulations (Lab Scale) Metronidazole Tablets (500 mg) 1........................ca......... crystalline [10] ..............4 Aerosil 200 [4] ................... Manufacturing (Wet granulation) Granulate mixture I with solution II.....................0..................220 II. Formulation I........................... Tablet properties Weight ...................................................755 mg Diameter .....6 min Friability ............0..........................biplanar Hardness ................................................ dry............5 Calcium arachinate [2] .......................... mix with III and press with medium compression force..178 N Disintegration ...............5 mg mg mg mg mg mg mg mg 2...6 % BASF Fine Chemicals Generic Drug Formulations 1998 .2........ 75 III....... pass through a 0.................................................................. Kollidon CL [1]......................................................... Kollidon 90 F [1] ..0................. 3.................

............................. Properties of the gel A clear colourless gel was obtained. Maintain the temperature until the air bubbles disappeared........ Metronidazol .......21............37.....1.......0 Lutrol E 400 [1]... II..................7 Formulations of semi-solid drugs (Lab scale) Metronidazol Vaginal Gel (1.......... BASF Fine Chemicals Generic Drug Formulations 1998 ...2 Lutrol F 127 [1] ..8 g g g g 2.......2 %) 1............................. 3............ Formulation I...............40...... Manufacturing Heat mixture I to 70 – 80 °C and slowly add the water heated to about 70 °C........6.......0 Water .

6.7 Formulations of semi-solid drugs (Lab scale)

Miconazole Cream
(2 %)

1. Formulation
I.

Cetylstearyl alcohol...................................7.0
Cremophor A 6 [1] ....................................1.5
Cremophor A 25 [1] ..................................1.5
Liquid paraffin ........................................12.0
Parabene(s)..............................................0.1
II. Water .....................................................67.8
III. Propylene glycol [1] ..................................8.0
Micronazole nitrate ...................................2.0

g
g
g
g
g
g
g
g

2. Manufacturing
Heat the mixture I and the water II separately to about 80 °C. Add the
water II to the obtained solution I with rigorous stirring. Heat III until the
active ingredient is dissolved, mix with I/II and continue to stir during
cooling to room temperature.

3. Properties
White cream.

4. Physical stability
No change of appearance or crystallization were observed during 6 weeks
at 45 °C.

5. Remark
This formulation could be used for other active ingredients too.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Miconazole Injectable Solution
(1%)

1. Formulation
I.
II.

Miconazole ..............................................1.0 g
Cremophor EL [1] ...................................12.0 g
Parabenes .................................................q.s.
Water for injectables ..........................ad 100 ml

2. Manufacturing
Heat mixture I to about 65 °C, stir well and add slowly the hot solution II.
After the ampoules have been heat-sterilized, they should be shaken for
a short time, while they are still hot, to eliminate any separation of the
phases that may have occurred. Sterilization can also be performed by
membrane filtration under pressure.

3. Properties of the solution
Clear colourless liquid having a low viscosity.

4. Remark
In Germany Cremophor EL must be declared on the labels of the
injectables.

BASF Fine Chemicals Generic Drug Formulations 1998

6.7 Formulations of semi-solid drugs (Lab scale)

Miconazole Mouth Gel
(2 %)

1. Formulation
I.

Miconazole nitrate (Sigma) ........................2.0
Orange flavour..........................................0.1
II. Lutrol F 127 [1] .......................................20.0
Cremophor RH 40 [1] ..............................10.0
Propylene glycol Pharma [1] ....................10.0
III. Kollidon 90 F [1] .......................................5.0
Saccharine sodium ...................................0.3
Water.....................................................52.6

g
g
g
g
g
g
g
g

2. Manufacturing
Dissolve I in the molten mixture II. Heat solution III to 90 °C and mix
slowly with I/II. Let cool to room temperature when the air bubbles
escaped.

3. Properties of the gel
A colourless, clear and soft gel was obtained having a orange like taste
and a slightly bitter after taste.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Mint Mouth Wash Solutions

1. Formulations

I.

II.

No. 1

No. 2

Mint oil .........................................................2.0 g
Menthol ......................................................0.04 g
Eucalyptus oil..............................................0.09 g
alpha-Bisabolol (BASF) ........................................–
Thymian oil .................................................0.06 g
Cremophor RH 40 [1] ....................................4.0 g
Saccharin sodium........................................0.45 g
Sodium citrate.............................................0.20 g
Citric acid ...................................................0.50 g
Sodium fluoride...................................................–
Glycerol ..............................................................–
Lutrol F 127 [1]..............................................5.0 g
Salicylic acid ...............................................0.06 g
Benzoic acid ...............................................0.10 g
Sorbitol, crystalline [10] ................................17.5 g
Ethanol 96 % ...............................................21.6 g
Sicovit colorant [1]..........................................q. s.
Water .........................................................48.4 g


1.0 g
1.0 g
1.0 g

4.0 g
0.45 g
0.20 g
0.50 g
0.02 g
5.0 g
5.0 g



6.7 g
q. s.
80.1 g

2. Manufacturing
Mix the components I and heat to about 60 °C. Prepare solution II, heat
to about 60 °C and add it slowly to the well stirred mixture I.

3. Properties of the solutions
Clear, coloured liquids having a fresh mint taste.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Mint Oil Solution
(3.5 %)

1. Formulation
Peppermint oil ..........................................3.5
Cremophor RH 40 [1] ..............................13.8
Ethanol 96 % ..........................................52.0
Water.....................................................30.7

g
g
g
g

2. Manufacturing
Mix the peppermint oil with Cremophor RH 40, stir well and add slowly
ethanol and water.

3. Properties of solution
Clear, colourless liquid of low viscosity.

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Multivitamin + Calcium + Iron Tablets
(1 RDA of Vitamins)

1. Formulation
Vitamin A acetate dry powder ...................5.0 g
500,000 i. u./g (BASF)
Vitamin D dry powder ..............................2.0 g
100,000 i. u./g (BASF)
Thiamine mononitrate (BASF) ....................1.2 g
Riboflavin (BASF)......................................1.8 g
Nicotinamide ..........................................12.0 g
Vitamin E acetate dry powder SD 50 ........4.0 g
(BASF)
Ascorbic acid, powder (BASF) .................50.0 g
Ferrous fumarate ....................................60.0 g
Dibasic calcium phosphate [9], .............200.0 g
granulated with 5 % Kollidon 30 [1]
Calcium carbonate................................125.0 g
Avicel PH 101 [5] ....................................45.0 g
Aerosil 200 [4] ..........................................1.5 g

2. Manufacturing (Direct compression)
Mix all components, pass through a sieve and press to tablets.

3. Tablet properties
Weight .................................................500 mg
Diameter ...............................................11 mm
Form ...................................................biplanar
Hardness..................................................75 N
Disintegration (water)...........................2 – 3 min
Friability...................................................0.3 %

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Multivitamin + Calcium Syrup
(1 RDA of Vitamins/20 ml)

1. Formulation
I.

Vitamin A palmitate ..............................10.0 mg
1.7 Mio. i. u./g (BASF)
Vitamin D 40 Mio. i.u./g........................0.05 mg
Vitamin E acetate (BASF) ....................100.0 mg
Butylhydroxytoluene ..............................2.0 mg
Cremophor RH 40 [1] ...............................4.5 g
II. Water .....................................................10.0 g
III. Saccharose ............................................45.0 g
Methyl parabene ................................200.0 mg
Citric acid............................................80.0 mg
IV. Glycerol ...................................................9.6 g
Calcium gluconate ..................................70 mg
Water.....................................................25.0 g
V. Thiamine hydrochloride (BASF) .............15.0 mg
Riboflavin 5’-phosphate sodium............15.0 mg
Nicotinamide .......................................55.0 mg
Pyridoxine hydrochloride (BASF) ...........15.0 mg
Ascorbic acid, crystalline (BASF).........300.0 mg
Sorbic acid ........................................100.0 mg
Propylene glycol Pharma [1] ......................5.0 g
Total amount ...........................................100 g

2. Manufacturing
Heat I and II separately to about 60 °C and mix slowly well stirring to
obtain a clear solution. Dissolve III in the hot solution IV to obtain a clear
solution. Mix the cool solutions I/II, III/IV and V and adjust the pH value
to 4.0 – 4.1. Pass during 10 min nitrogen through the solution and fill in
flasks under nitrogen.

BASF Fine Chemicals Generic Drug Formulations 1998

3. Chemical stability (20–25 °C; HPLC methods)
The following stability data were obtained with the same syrup but without calcium gluconate:

Vitamin
Vitamin
Vitamin
Vitamin

A
B1
B2
C

BASF Fine Chemicals Generic Drug Formulations 1998

(9 months)

(12 months)

86 %
88 %
96 %
78 %

73 %
83 %
92 %
77 %

2.9 Tablet formulations (Lab Scale)

Multivitamin + Carbonyl Iron Tablets
(1 – 2 RDA of Vitamins)

1. Formulation
Vitamin A acetate dry powder
500,000 i. u./g (BASF) .............................10.0 g
Thiamine mononitrate (BASF) ....................2.2 g
Riboflavin (BASF)......................................2.2 g
Nicotinamide ..........................................16.5 g
Calcium D-pantothenate (BASF) ..............11.5 g
Pyridoxine hydrochloride (BASF)................2.2 g
Cyanocobalamin, dry powder 0.1% ..........6.0 g
Ascorbic acid, powder (BASF) .................85.0 g
Vitamin E acetate dry powder SD 50 .......31.0 g
(BASF).............................................................
Ludipress [1].........................................311.0 g
Carbonyl iron powder OF (BASF) .............10.0 g
Magnesium stearate [2].............................3.0 g
Orange flavour..........................................7.2 g
Saccharin sodium.....................................2.5 g

2. Manufacturing (Direct compression)
Mix all ingredients, pass through a 0.8 mm sieve, mix and press with
high compression force (20 kN).

3. Tablet properties
Weight .................................................500 mg
Diameter ...............................................12 mm
Form ...................................................biplanar
Hardness..................................................69 N
Disintegration.........................................12 min
Friability...................................................0.2 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Multivitamin + Minerals Tablets with Beta
Carotene
(2 RDA of Vitamins)
1. Formulation
No. 1

No. 2

Beta carotene dry powder 10 % ..................150.0 g
Thiamine mononitrate (BASF) .........................2.5 g
Riboflavin (BASF)...........................................2.9 g
Pyridoxine hydrochloride (BASF) ....................2.0 g
Nicotinamide...............................................22.0 g
Calcium D-pantothenate (BASF) ...................12.0 g
Ascorbic acid for direct compression ..........110.0 g
(Roche)
Calcium phosphate, dibasic [9] ..................550.0 g
Ferrous fumarate .........................................82.0 g
Magnesium oxide ......................................166.0 g
Cupric sulfate................................................2.5 g
Manganese sulfate ......................................13.8 g
Potassium chloride ......................................57.2 g
Zinc sulfate .................................................37.0 g
Avicel PH 102 [5] .........................................57.0 g
Kollidon CL [1] ............................................50.0 g
Stearic acid [7] ..............................................5.7 g
Magnesium stearate [2] .................................5.0 g

50.0 g
3.0 g
3.0 g
3.0 g
22.0 g
12.0 g
100.0 g
550.0
80.0
160.0
2.0
14.0
50.0
37.0
60.0
50.0
6.0
5.0

g
g
g
g
g
g
g
g
g
g
g

2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high
compression force.

BASF Fine Chemicals Generic Drug Formulations 1998

..............................................................1300 mg Diameter . Tablet properties No..........................................................................biplanar Hardness ............. 1 No........ 2 Weight ...16 mm Form ...3....... 2 (20–25°C) Storage time Beta Carotene B1 B2 B5 B6 6 Months 12 Months 100 % 92 % 98 % 96 % 98 % 92 % 100 % 97 % 99 % 96 % 5................94 N Disintegration (water).................................< 1 min Friability .............. Chemical stability of formulation No......................1% 1205 mg 16 mm biplanar 88 N < 1 min < 0............1% 4............ BASF Fine Chemicals Generic Drug Formulations 1998 C 95 % 94 % .................. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application.................

........30...............................................6....................................................3..1% dry powder ../g (BASF) Thiamine mononitrate (BASF) ...000 i..1......2 g Riboflavin (BASF)........0 g Vitamin E acetate .....20......................... BASF Fine Chemicals Generic Drug Formulations 1998 .5....5 g (BASF) Ascorbic acid.....................7.....1...0 g Passion fruit flavour...............1.1....................0 g Vitamin D 3 acetate dry powder 100...8 mm sieve and press with medium to high compression force (20 kN).......0 g Aerosil 200 [4] ....0 g dry powder SD 50 (BASF) Sorbitol..0 g 2... crystalline.......................6...0 g Raspberry flavour.......60..........0 g Orange flavour........... dry powde ..8 g Cyanocobalamin 0......31........20........0 g 500.......0 g Kollidon VA 64 [1] ... dry powder ........................... Manufacturing (Direct compression) Mix all ingredients............... u....200............. powder (BASF) .9 Tablet formulations (Lab Scale) Multivitamin Chewable Tablets for Children 1..... crystalline [10] .0 g Pyridoxine hydrochloride (BASF)....000 i...... dry powder..2... u...200........./g (BASF) . pass through a 0...2.................0 g Sucrose................... Formulation Vitamin A acetate dry powder...............0 g Cyclamate sodium.2 g Nicotinamide .......

............................12 mm Form ..............biplanar Hardness ...............................................0...........100 N Disintegration ....................................... Tablet properties Weight ........................................7 min Friability........2 % BASF Fine Chemicals Generic Drug Formulations 1998 ..............................................................................................575 mg Diameter .3.........

........0............................013 g Vitamin E acetate (BASF) . Properties Clear or slightly opalescent yellow liquid of low viscosity and pH 4..........0.......................0..........02 g Propylene glycol Pharma [1] ........0 g Water ......8 g 1....... stir strongly and add slowly solution II (60 °C)...... BASF Fine Chemicals Generic Drug Formulations 1998 .... Hydrochloric acid ...... u............./g .....0........5.........0 g (or Cremophor RH 40) [1] II........15..2 g Sodium bisulfite........100 g 2..................................2 g Water....../g (BASF) Vitamin D 3 40 Mio......4 g Riboflavin 5-phosphate sodium ..5 g III.q.................. Adjust the pH with IV to about 4.......... Vitamin A palmitate... Thiamine hydrochloride (BASF)....................... Parabenes ..0..... To the obtained clear solution add solution III.......................0 g IV.5 g Cremophor EL ............ Formulation I....0..... i................................2 g Nicotinamide ... u............... Total amount ..............................20.......s.................. Manufacturing Heat mixture I to about 60 °C....10............8 Liquid Formulations (Lab scale) Multivitamin Drops 1..7 Mio.....2 g Pyridoxine hydrochloride (BASF).0.................. 3.............. i.....0....52..........0..........................................

...........40.........................................................0.................1..2.............................................. Kollidon VA 64 [1] .......4.....30 g Nicotinamide ...........U...........25 g Calcium D-pantothenate (BASF) .........10 g Cyanocobalamin gelatin .................... Formulation I.....0...............25...00 g Isopropanol .0... BASF Fine Chemicals Generic Drug Formulations 1998 ................4 Formulation of granules.............2...66 g coated 0.......... Thiamin hydrochloride (BASF).... Manufacturing Granulate mixture I with solution II........0..00 g Citric acid .............1..... powder (BASF) .......130............................/g CWD (BASF) ...8 mm sieve................... Fill 3 – 4 g in sachets..............0......./g CWD (BASF) ............000 I..........00 g III..00 g Saccharine sodium ...00 g Fructose ............00 g 2...50....000 I......80 g Vitamin E acetate dry powder 50 %..00 g Sucrose ....................20......10 g Pyridoxine hydrochloride (BASF)...............................20...U.....50 g Ascorbic acid..50 g Vitamin D 3 dry powder 100.....26 g Riboflavin (BASF) . pass through a 0... dry syrups and Iyophylisates (Lab scale) Multivitamin Effervescent Granules (1 RDA of Vitamins) 1...35...00 g Kollidon CL-M [1]... Vitamin A acetate dry powder 325.............................80...........1% (BASF) Sodium bicarbonate ....................10 g II........00 g Flavours ..0......1.....................00 g Cyclamate sodium .................................. dry well and mix with III..15.....

3. Administration 3 – 4 g of the granules (= 1 sachet) correspond to about 1 RDA of the vitamins BASF Fine Chemicals Generic Drug Formulations 1998 . Properties of the granules Colour: Flowability: Dispersibility: Yellow granules Very good 4 g disperse homogeneously in water after about 40 seconds. 4.

.....................................1 min Friability......................................11 g Tartaric acid powder ..............................1% (BASF) ......2.............................16 mm Form ....... Manufacturing (Wet granulation) Granulate mixture I with solution II prepared at 70 ºC...............s....9 % BASF Fine Chemicals Generic Drug Formulations 1998 ............................ Formulation I........................................biplanar Hardness ............................85 g Vitamin E acetate dry powder 50 % .....................107 N Disintegration (water) ...... 2...................23 g Cyanocobalamin..............600 g Flavours ...............300 g Corn starch [3] ....................... add III..........................2 g Riboflavin (BASF)....... powder (BASF)...............100 g II... pass through a 0..22 g Calcium D-pantothenate (BASF) . Food (1 – 2 RDA of Vitamins) 1..50 g III...........................40 g Sodium bicarbonate ..............................2 g Pyridoxine hydrochloride (BASF)........................... dry and sieve..................... Thiamine mononitrate (BASF) ............9 Tablet formulations (Lab Scale) Multivitamin Effervescent Tablets with Beta Carotene............................................................................q.................4 mm sieve and press with high compression force at maximum 30 % of relative atmospheric humidity....6 g Ascorbic acid.................................................3 g Water........ powder 0.......2 g Nicotinamide ....1630 mg Diameter .........80 g Saccharin sodium....................................................... Tablet properties Weight ................ Beta carotene dry powder 10 % CWD Food grade (BASF) ...................0... 3......400 g Lactose monohydrate [8] ............ Corn starch [3] .

4. Remark All components of this formulation are allowed in Europe for food application. BASF Fine Chemicals Generic Drug Formulations 1998 .

.........17 mg Tartaric acid...........100 mg 2.60 mg Polyethylene glycol 6000. Formulation I...... mix with III and press with high compression force at maximum 30 % of relative atmospheric humidity.............. Thiamine mononitrate (BASF) .......................4 mg Pyridoxine hydrochloride (BASF) ...............300 mg Kollidon 30 [1] ... Kollidon 30 [1] ............................................. Riboflavin (BASF) ..... powder ..............................360 mg Sodium bicarbonate.................300 mg Sucrose................................................20 mm Form .2............................................11 mg Nicotinamide ....2500 mg Diameter ...biplanar Hardness ....../g dry powder CWD (BASF) Vitamin E acetate dry powder 50 % ............66 mg Calcium D-pantothenate (BASF) ...... dry at 60 ºC with vacuum.... powder (BASF) .............................. Manufacturing (Wet granulation) Granulate the mixture I with solution II...1% dry powder ...9 Tablet formulations (Lab Scale) Multivitamin Effervescent Tablets I 1........12 mg 250000 i...............................80 mg Kollidon CL [1] ..... powder [6] .........................about 80 mg III..................... Tablet properties Weight .550 mg Cyanocobalamin 0................13 mg Riboflavin (BASF) ................ powder .........................................................20 mg Vitamin A palmitate ........................................... u.......................................6 mg Ascorbic acid...35 mg II........................ 3................................. crystalline.......140 N BASF Fine Chemicals Generic Drug Formulations 1998 ...5 mg Isopropanol ...............................550 mg Sucrose....................

.................................. Chemical and physical stability (20–25 ºC) 6 Months 12 Months Ascorbic acid Cyanocobalamin Vitamin A All other vitamins 100 % 91% 80 % > 94 % 92 % 92 % 69 % > 94 % Hardness 140 N BASF Fine Chemicals Generic Drug Formulations 1998 ...Disintegration (water) ..........1% 4.....1 – 2 min Friability...............................

.5 g 60............5 g Pyridoxine hydrochloride (BASF) ............................ powder ......../g CWD (BASF) .........5 g Cyclamate sodium. powder [6]............................ BASF Fine Chemicals Generic Drug Formulations 1998 ....– Tartaric acid.0 g 50....... u.0 g 500.......0 g 30...0 g Fructose .........1% dry powder .......0 g 200...........200.....................600.. powder ..........2..5 g 5......30...100.30....0 g 70.......5 g Ribolfavin (BASF).70.................................0 g Saccharin sodium ...0 g 200.......200...0 g Ascorbic acid.....20.........................................5 g Nicotinamide ..0....... sieve through a 0.....8 mm screen and press with high compression force at maximum 30 % relative atmospheric humidity...0 g 30....5 g 40....110..................0 g Citric acid.....................9 Tablet formulations (Lab Scale) Multivitamin Effervescent Tablets II (3 – 4 RDA of Vitamins) 1...6...0 g 0.0 g Vitamin E acetate dry powder 50 % ...0 g Sucrose..................0 g 2.60......................... Manufacturing (Direct compression) Mix all components.............0 g Polyethylene glycol 6000................0 g Ludipress [1] ....500.......................5 g 6.40..5.......... powder (BASF)....0 g – 500....0 g Calcium D-pantothenate (BASF).0 g Cyanocobalamin 0......................5....0 g 500.......................200.....0 g 100. Formulations No........0 g Flavours (Firmenich) .............0 g 20.... crystalline ....0 g Sodium bicarbonate .0 g 5..........................0 g 200.. 1 No.400.....0 g Vitamin A palmitate dry powder 325000 i..... 2 Thiamine mononitrate (BASF) ............

..........................................................................2200 mg Diameter ......................... 2 Weight ...............................4 % 4..1...3..................98 N Disintegration (water)................................................................20 mm Form .....................................................biplanar Hardness ........93 % Vitamin B 6 ..> 95 % BASF Fine Chemicals Generic Drug Formulations 1998 ........... 1 No......................................................0 % 2495mg 20 mm biplanar 197 N 2 min 0.........................88 % Vitamin A .................................. Tablet properties No... HPLC) Vitamin B 1 .........89 % Vitamin B 12 ....................................79 % All other vitamins................................................1 – 2 min Friability . 1 (after 12 months at 20–25 ºC................................. Chemical stability of formulation No...........................

.. i.5..........5 Mio..... Preservative .................1 g Butylhydroxytoluene ..0............ Water for injectables .........2.6 g EDTA sodium ...................5 g 2.......0.... stir well and add very slowly the hot solution II............. Prepare solution III and add to the cool mixture I/II..4....0....................... i..................1.........6 g 0.....6................1 g 0...............................................................1......................... u......0 g q............5 g 0.......s.........6 g 10 mg ad 10 ml Total amount....0 g 22.100 ml 100 ml I...................5 g Benzyl alcohol.....0.....1 g 0.....................1 g 0..ad 90 ml III.......1 g Thiamine hydrochloride......../g (BASF) Vitamin D 3 (Cholecaciferol) ...................ad 10 ml 4./g Vitamin E acetate (BASF) .........8 Liquid Formulations (Lab scale) Multivitamin Injectable for Veterinary Application 1............ Nicotinamide ............ u..5 g 1... ad 90 ml 1..................0 g Solutol HS 15 [1] ..6 g Riboflavin phosphate sodium .........................................1 g Pyridoxine hydrochloride.5 g 2........s.................10 mg Water ....... Manufacturing Heat mixture I to about 65 °C......5 g Dexpanthenol....... 1 Emulsion No.....0.........0 g II..27 mg 40 Mio.................. 2 Solution Vitamin A propionate ............................. 27 mg 2........ Formulations No.......... BASF Fine Chemicals Generic Drug Formulations 1998 .....................................q.............................

Solution (formulation No.1. Properties Emulsion (formulation No.5.3. 1) A yellow milky emulsion was obtained having a viscosity below 5 mPa · s and a pH of 4. BASF Fine Chemicals Generic Drug Formulations 1998 . 2) A clear yellow solution was obtained having a viscosity of about 7 mPa · s and a pH of 4.

......000 g Kollidon CL-M [1].....................1%............150 g Vitamin E acetate dry powder ...4. BASF Fine Chemicals Generic Drug Formulations 1998 ......................000 g Ethanol or Isopropanol .22 g Calcium D-pantothenate (BASF) ................................200 g Thiamine mononitrate (BASF) . II.110 g Pyridoxine hydrochloride (BASF)...................2....U....5............150 g Cyanocobalamin 0.........000 g Kollidon VA 64 [1] .8 mm sieve and granulate with solution II in the fluidized bed... Vitamin A+D dry powder 250..... If the technology of a fluidized bed is not available..........................20.......................... finely ground ...66 g gelatin coated (BASF) Ascorbic acid powder (BASF) ...../g CWD (BASF) ....26 g Riboflavin (BASF)....1.4 Formulation of granules......000 + 50......................................... Formulation I.....approx... Administration Suspend 6 –12 g (= 1 sachet) in a glass of water corresponding to 2 – 4 RDA of vitamins.000 I.... 7 l 2........33 g Nicotinamide ...............000 g Orange flavour....... E and B 12 should be added after the granulation of the other components.... dry syrups and Iyophylisates (Lab scale) Multivitamin Instant Granules (2 – 4 RDA of Vitamins) 1....... the dry powders of vitamin A........................ 3.........................210 g SD 50 (BASF) Sucrose..........1.... Fill 6 –12 g of the granules in sachets. Manufacturing Pass mixture through a 0.......

........ Stability (after 12 months........ HPLC) Vitamin C.... Properties of the suspension The multivitamin suspension is prepared prior to application by shaking the granules with water.> 95 % BASF Fine Chemicals Generic Drug Formulations 1998 ........ yellow suspension thus obtained shows no sedimentation over a period of some hours..... 5........... The uniform..............4.......91% Calcium pantothenate ...................... 20–25 °C........... The redispersibility is very easy...........not tested All other vitamins ........

....060 mg Butylhydroxytoluene............355 mg Riboflavin (BASF) ..........300 mg Ferrous sulfate (7 H2 O) ...................100 g V Lutrol F 127 [1] ..........725 g III.....35 mg (BASF) Nicotinamide ..............about 1000 g 2...100 g Total amount: .......438 mg Manganese chloride (4 H 2 O) ................................. Manufacturing Heat mixture I to about 60 °C to obtain a clear solution.............. Vitamin A palmitate .......................7 Formulations of semi-solid drugs (Lab scale) Multivitamin Oral Gel (vet....................110 mg 1................................................ Water.......................35 mg Dexpanthenol (BASF) .... add slowly the water II to the well stirred solution I.......... cool to about 6 °C..... Kollidon 90 F [1] ...... add V and stirr until all Lutrol F 127 is dissolved........................................353 mg Folic acid ................ i......7 Mio........ Maintain the cool temperature until the air bubbles escaped..........1........35 mg Pyridoxin hydrochloride (BASF) ............................... Formulation I............ BASF Fine Chemicals Generic Drug Formulations 1998 ..................20 g II.............................. Thiamine hydrochloride (BASF) ........50 g Lutrol F 127 [1] .638 mg Potassium iodide .............353 mg EDTA sodium.......6......................................../g (BASF) Vitamin E acetate (BASF)....................... dissolve III and IV in this mixed solution at room temperature......177 mg Cyanocobalamin gelatin coated 1% ..............u.............) 1......................115 mg IV........................................500 mg Cremophor RH 40 [1] ......

......3.................................3 Consistency.............opalescent pH-value............ Properties of the gel Colour .semi-solid BASF Fine Chemicals Generic Drug Formulations 1998 ....yellow-orange Clarity ..........................................4....................................................................

6.... Lutrol F 127 [1] ................................. Thiamine hydrochloride (BASF) ....................3 mg Pyridoxin hydrochloride (BASF) .... Total amount: .....................3 mg Riboflavin (BASF) .0 g III...........u..7 Formulations of semi-solid drugs (Lab scale) Multivitamin Oral Gel with Linoleic Acid and Linolenic Acid 1................................................. Maintain the cool temperature until the air bubbles escaped......150 µg Cremophor RH 40 [1].................50 mg Ascorbic acid..20.10 µg Calcium D-pantothenate (BASF) ........5............ Formulation Evening Primrose Oil (Epopure®.............. Water...0 g II...... Prima Rosa/SA) .........5.............7 Mio...................14..15 mg Cyanocobalamin..... crystalline (BASF) .............0 g IV......... Properties A clear yellow gel was obtained.........19 mg Vitamin D 3 40 Mio i....55.../g (BASF) Vitamin E acetate (BASF)...0 g Lutrol F 127 [1] ..10 mg Nicotinamide ...............30 mg 1..... Cool the obtained solution to about 5 °C and dissolve the rest of Lutrol F 127 (= IV).... crystalline .... BASF Fine Chemicals Generic Drug Formulations 1998 ........................ 3........................................................................ i..1......................0 ml Vitamin A palmitate ..../g ................. Dissolve at 20 – 25 °C the components III in this clear solution I/II............about 100 g 2........ Add the warm water II (65 °C) slowly to the well stirred mixture I. Manufacturing Prepare mixture I and heat to about 65 °C..........u....0 g I..

BASF Fine Chemicals Generic Drug Formulations 1998 .45 g gamma-linolenic acid. Remark 5 ml of Evening Primrose Oil Epopure contains 3.4.5 g linoleic acid and 0.

.................................300.......0 mg Nicotinamide ..................0 g Methyl parabene ...................... Vitamin D 40 Mio................ Glycerol .........5 g II........55................................5............0 mg Riboflavin 5’-phosphate sodium........8 Liquid Formulations (Lab scale) Multivitamin Syrup.0 g Total amount ....... Saccharose ...............05 mg Vitamin E acetate (BASF) .......0 mg IV..................................2.....0 mg Cremophor RH 40 [1] .................................7 Mio....15.................80...... i...........6 g Water.0 mg Propylene glycol Pharma [1] .....................................25......../g (BASF) ..0 mg Sorbic acid ....10............. BASF Fine Chemicals Generic Drug Formulations 1998 ...... Thiamine hydrochloride (BASF) ........0 mg Pyridoxine hydrochloride (BASF) ......45................ i... Water .....0 – 4...... Manufacturing Heat I and II separately to about 60 °C and mix slowly well stirring to obtain a clear solution.....4.0 mg Citric acid.... Pass during 10 min nitrogen through the solution and fill in flasks under nitrogen...0 mg 1..............10........................................15...........2. Vitamin A palmitate ... Formulation I..100 g 2..9.. Mix the cool solutions I/II........0 mg Butylhydroxytoluene ......u................0 g III......... III/IV and V and adjust the pH value to 4..0 g V. crystalline (BASF)....100.......100............ I (1 – 2 RDA/20 ml) 1......... Dissolve III in the hot solution IV to obtain a clear solution......................................................5..... u..15..0........../g...200.......................0 mg Ascorbic acid.

HPLC methods) Vitamin Vitamin Vitamin Vitamin A B1 B2 C BASF Fine Chemicals Generic Drug Formulations 1998 (9 months) (12 months) 86 % 88 % 96 % 78 % 73 % 83 % 92 % 77 % . Chemical stability (20–25 °C.3.

................................. Sugar syrup USP..............ad 100 ml 2........00 g III............. Manufacturing Heat mixture I to about 65 °C.. 4..................1......0...0 mg Cremophor RH 40 [1]......5....................0.....u..... II 1........0.. Thiamine hydrochloride (BASF) .....17... crystalline (BASF) ..3......... Parabenes ......0 mg 1... Properties of the syrup Clear................17......25 g Water ./g (BASF) Vitamin D 3 40 Mio i.....00 g II....... Vitamin A palmitate ..8 Liquid Formulations (Lab scale) Multivitamin Syrup........02 g Pyridoxine hydrochloride (BASF).....02 g Ascorbic acid....... BASF Fine Chemicals Generic Drug Formulations 1998 .........05 g Riboflavin phosphate sodium ............10 g Water ..0... u..............0. Physical stability (20–25 °C protected from light) No change of the appearance after 3 months..0......... 3...... yellow viscous liquid.... Formulation I.7 Mio i.............................................. Mix with solution III and add the syrup IV.....................1 mg Butylhydroxytoluene ............./g ... stir well and add very slowly the warm solution II (65 °C).................5 g IV..

...2.2 g Nicotinamide .........0 g Microcrystalline cellulose.......... Manufacturing (Direct compression) Mix all components.9 Tablet formulations (Lab Scale) Multivitamin Tablets I (1 – 2 RDA of Vitamins) 1.......................................0 3......./g (BASF) ..2..7.......0 g 500....0 g – 300.......... Formulation No......85.....................5 g g g g 2......................2 g 16...0 g 2.... u..................0 g Vitamin E acetate dry powder SD 50 ..000 i.......0 g Orange flavour .............5 g 2.........0 g 21........2.0 g 31.... pass through a 0........2 g Cyanocobalamin 0...0 g Ascorbic acid.....10....16.0 g 85.....................31......................2 g 2. mix and press with medium compression force (15 kN).....321......3....................2 g Saccharin sodium .....– (Rettenmaier) Kollidon VA 64 [1].. powder (BASF)......– Magnesium stearate [2] ............... BASF Fine Chemicals Generic Drug Formulations 1998 ............5 g 11..11.......0 g (BASF) Ludipress [1] ..................................2 g 6....................................0 7...5 g Calcium D-pantothenate (BASF) ........................5 g 10...2..1% dry powder. 1 No...2 g Ribolfavin (BASF)....... Vitacel ® ..........................2.....6.....8 mm sieve....... 2 Vitamin A acetate dry powder .....5 g Pyridoxine hydrochloride (BASF) ............... Thiamine mononitrate (BASF) ...........2 2...

................ Tablet properties No............................ 1 No..............................90 % Vitamin B 12 All other vitamins..94 % Vitamin B 6 Calcium D-pantothenate .............1% 4.............................................................5 min Friability ..........................68 N Disintegration (water) ..............................................................88 % ... 2 Weight ...biplanar Hardness .....................................2 % 501 mg 12 mm biplanar 195 N 6 min < 0........92 % .............3...............................................> 95 % BASF Fine Chemicals Generic Drug Formulations 1998 ................ Chemical stability of formulation No.....................................................500 mg Diameter . 1 (after 12 months at 20–25 ºC) Vitamin A ..................................................0............................12 mm Form .............................

............... Manufacturing (Wet granulation) Granulate mixture I with solution II....................20........ Kollidon 30 [1] or Kollidon VA 64 [1] ...............11.............0 Nicotinamide .......0 Isopropanol ..................................100 N Disintegration (water).............................................................................0 Vitamin E acetate dry powder SD 50 (BASF) ................2 Riboflavin (BASF) ....0 g g g g g g g g g g g g g g g g 2........1% BASF Fine Chemicals Generic Drug Formulations 1998 .........................2 Calcium D-pantothenate (BASF) . Vitamin A acetate + Vitamin D 3 dry powder 500.............7..........................1 – 2 min Friability ........................6. 80 III.................0 Pyridoxine hydrochloride (BASF).......................................0 Ascorbic acid..............65............../g (BASF)..ca...................................... mix with the components III and press with medium compression force..................2 Mannitol ..12 mm Form ......................300.....................................000 + 50...........0 Magnesium stearate [2]........................... crystalline (BASF) ..............................................0 Cyanocobalamin gelatin coated 0..........2... u................2............11.........0 II..................................................................0 Saccharin sodium.................................biplanar Hardness.80................................................. pass through a 0......... Tablet properties Weight ................3............2..................... Formulation I...... Thiamine hydrochloride (BASF) .2.0 Avicel PH 101 [5] ....................................................................................................................................560 mg Diameter .................1% (BASF) ................................< 0.............2......9 Tablet formulations (Lab Scale) Multivitamin Tablets II (1 – 2 RDA of Vitamins) 1............................20..................31.0 Orange flavour....................................................... dry............ 3......8 mm sieve...................................................................000 i..............

500 i. u. Chemical stability of vitamins A and C (20–25°C. u.500 i./g = 92 % Vitamin C 85 mg = 106 % 82 mg = 102 % 77 mg = 96 % BASF Fine Chemicals Generic Drug Formulations 1998 . closed) 0 Months 3 Months 6 Months Vitamin A 15./g = 100 % 15.4./g = 100 % 14. u.300 i.

............................................ B 6 and folic acid ..11 mm Form ..2 g Ludipress [1] .......69........................................3.... Manufacturing (Direct compression) Pass all components through a 0.....conform to DAB BASF Fine Chemicals Generic Drug Formulations 1998 .............. Formulation Vitamin mixture (BASF.... 3................................9 Tablet formulations (Lab Scale) Multivitamin Tablet Cores with Beta-Carotene (1 – 2 RDA of Vitamins) 1.............................13 min Friability ...................8 mm sieve....................................... Tablet properties Weight ..............................97 N Disintegration (water)........... mix and press with high compression force....0 % Content uniformity of Vitamin B1......270... see “Remark”)....3 g 2...................459 mg Diameter .............. B 2............biconvex Hardness.................1 g Magnesium stearate [2]....2....................

...........................28.................000 i.........50 % Calcium D-pantothenate ..........11./g Beta carotene dry powder BetaVit 10 % ....15 % Cyanocobalamin gelatin coated 1% .........1.....1...............50 % Thiamine mononitrate................91% Folic acid ..........11.................20 % Vitamin D 3 dry powder 100...96 % Nicotinamide....... u...............86 % D-Biotin..............000 i............/g ....................27 % 500.........1..4........40 % Phytomenadione dry powder 5 % GFP.. 1% trituration ................1...2...............................1......91% Pyridoxine hydrochloride ...09 % Ascorbic acid...............................0..... u...0........... Remark The used vitamin mixture had the following composition: Vitamin A acetate dry powder ....76 % Vitamin E acetate dry powder 50 DC..............0.............19 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........38..............24 % Riboflavin ...0......

.........0 g Magnesium stearate [2].....5 g (BASF) Folic acid ..............................................................20.....0......0.....0 g Pyridoxine hydrochloride (BASF)............0 g 2....0..............5 g Riboflavin (BASF)........ Manufacturing (Direct compression) Pass all components through a 0.....9 Tablet formulations (Lab Scale) Multivitamin Tablets for Dogs 1....4.05 g Choline bitartrate ............1......0..........0 g Calcium D-pantothenate (BASF)..............5.7 g Nicotinamide ............7 min Friability ..biplanar Hardness. Formulation Vitamin A + D 3 dry powder ....................... u........ 3.....................5 g Cyanocobalamin gelatin coated 1% ..........................20......................................... mix and press with low compression force...............250 mg Diameter ...2.......000 + 50..0 g Vitamin E acetate dry powder SD 50 ........................0 g 500.......................0 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................................................0 g (BASF) Ludipress [1] ........8 mm Form ......0.......................000 i......................../g (BASF) Thiamine mononitrate (BASF) ......................2...........196....................................... Tablet properties Weight ...............................8 mm sieve.........77 N Disintegration (water) .......

.................0 g – 70......– Pharma (BASF) Thiamine mononitrate (BASF) .... Manufacturing (Direct compression) Mix all components..................2 g 6.. Formulations No......0 7................0 g Vitamin E acetate dry powder SD 50 ...................0 g (BASF) Ludipress [1] ..........2............9 Tablet formulations (Lab Scale) Multivitamin Tablets with Beta Carotene (1 – 2 RDA of Vitamins) 1..............0 g Nicotinamide .......0 g Cyanocobalamin 0....0 g Kollidon VA 64 [1]..............................5 g 11.....10...0 7..............................0 g Ascorbic acid.............0 2......2 g 2....... Beta Carotene dry powder 10 % ................5 g 2...........0 g Orange flavour ........0 g 85..........2...2.........321.– Magnesium stearate [2] ..................5 g g g g g 2................... 2 Beta Carotene dry powder 10 % Betavit ® .2............1% dry powder........... 1 No..........8 mm sieve..31.......0 g (BASF) ..........0 3.......16...........3................85.............0 g Riboflavin (BASF). mix and press with medium compression force..0 g Pyridoxine hydrochloride (BASF) ..........2 g 6....0 g 210........2................0 g Saccharin sodium ....0 g 32.................7..... BASF Fine Chemicals Generic Drug Formulations 1998 ..............6........... pass through a 0...11.. powder (BASF)...............0 g Calcium D-pantothenate (BASF) ..............0 g 2....

............................... BASF Fine Chemicals Generic Drug Formulations 1998 ................ Chemical stability of vitamins in formulation No....5 min .... 2 .. 1 could be commercialized in Europe as dietary food because all components are allowed for this application.........< 0..................................................15 % 4......3.......... HPLC) Storage time Beta Carotene B1 B2 6 Months 12 Months 100 % 100 % 100 % 90 % 98 % 87 % B5 B6 100 % 98 % 100 % 97 % C 96 % 94 % 5......508 mg ........ Tablet properties Weight Diameter Form Hardness Disintegration Friability No............12 mm ............................................ 1 No......1% 449 mg 12 mm biplanar 47 N 10 min 0................. 1 (20–25°C.72 N (water) ......biplanar ....................... Remark Formulation No.........

keep it during 5 min under nitrogen bubbles... Sodium ascorbate crystalline ................/g ................44 mg II.....................................4.................................. filter through a 0..............40 mg 1.............................. Vitamin A palmitate .....u....252 mg Sodium hydroxide............... pass nitrogen through the solution and fill in ampules under nitrogen.2...... solution 1 molar .......0....0 ml Water for injectables ...110 mg Riboflavin phosphate sodium. 0.............. Adjust the pH to about 7..............................9.......0 g Lutrol E 400 [1]................ i...............2....2 mg Butylhydroxytoluene .2 µm membrane and fill in ampules under nitrogen............................... BASF Fine Chemicals Generic Drug Formulations 1998 .0 ml Chamber 2: I........... Formulations Chamber 1: I.5.. Chamber 2: Dissolve the mixture I in the buffer solution II.4 ml Hydrochloric acid...........200 mg Vitamin D 2 40 Mio.......... i.............................8 mg Propylene glycol Pharma [1] .......................................... Sterilize at 120 °C during 10 min............1 molar ......../g (BASF) Vitamin E acetate (BASF)...0 g II..................440 mg Pyridoxine hydrochloride (BASF) ...........7 Mio..................0...2 g Dexpanthenol (BASF) ....1....6 ml 2...........u...........2...............6 mg Butylhydroxyanisol .....66 mg Nicotinamide ............... Thiamine hydrochloride (BASF) ....2.................... Parabenes ..................................... Manufacturing Chamber 1: Heat mixture I to 60 °C.......8.......0 g III...30. add slowly the water of the same temperature and mix with solution III... The pH-value is about 4... Water.70.18 mg Citric acid............8 Liquid Formulations (Lab scale) Multivitamin Two Chamber Ampules 1.4 mg Solutol HS 15 [1] ....300 mg Folic acid .

....3...............................................................................................................................90 % Nicotinamide:..................... Chemical stability (Vitamin contents after 12 months at 20–25°C............................................................100 % Vitamin B 6: .................93 % Vitamin B 2: ..................... HPLC) Vitamin A: ..............97 % Vitamin C: ............................not determined Folic acid:............................................91% Vitamin B 1: ..............75 % Dexpanthenol: ...94 % BASF Fine Chemicals Generic Drug Formulations 1998 .....

.............15 Water ........9 Tablet formulations (Lab Scale) Nalidixic Acid Tablets (500 mg) 1.................59 % (60 min)................................................................104 N Disintegration (water) ......73 % BASF Fine Chemicals Generic Drug Formulations 1998 ...500 Kollidon 30 [1] ......... II.........8 mm-sieve........................................ Formulation I......1 min Friability....... Manufacturing (Wet granulation) Granulate I with the solution II........... add the mixture III...........................................................................125 III...........................25 Magnesium stearate [2] ..... Tablet properties Weight ...........................0.................... mix during 10 minutes....12 mm Form ........ dry and pass through a 0....... 3..biplanar Hardness ..............5 g g g g g 2............ Nalidixic acid ........ Kollidon CL [1] .....................................2......................................................... pass again through a 0......................................................8 mmsieve and press with low compression force (10 kN).........4 % Dissolution (30 min).....545 mg Diameter ............

1 g AcDiSol [5] . Tablettose [8].............................................................................................. add III and press with low compression force....................... Formulation I...............................................2..............441 mg Diameter .......................................2 min Friability..............8 mm sieve.................. Kollidon 90 F [1] .10 g 2.......250 g Kollidon 90 F [1] ......................4 g Water................................. Tablet properties Weight ..... Naproxen (Midas) ............0..................................................................................9 Tablet formulations (Lab Scale) Naproxen Tablets (250 mg) 1..47 N Disintegration ............................................ dry...1 g Polyethylene glycol 6000.........12 mm Form .................................. 3................................................................biplanar Hardness........... Manufacturing (Wet granulation) Granulate mixture I with solution II......... powder [6] ..................150 g Stearic acid [7] ...................41 g III.10 g Magnesium stearate [2] ..............4 g Cremophor RH 40 [1] ............6 g II......................... pass through a 0.........5 % BASF Fine Chemicals Generic Drug Formulations 1998 .....

..........3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................... pass through a 0................... Manufacturing (Wet granulation) Granulate mixture I with solution II.....biplanar Hardness............0 g III.......... 1 No.... pH 7.........0 g 2......... 1 No................9 % 94...........25...0 g I...5 g 10...........100 N Disintegration ....................9 Tablet formulations (Lab Scale) Naproxen Tablets (450 mg) 1...............3 % 86.................................0 g 90...........4 (10 min) ....................................0. Kollidon 30 [1] ... 2 Naproxen (Syntex) ......457...........................................– 457..................5 % (30 min).8 mm sieve................85......................... Magnesium stearate (Merck) ................................0 g II......................................... Formulations No.............................................5 g Kollidon CL [1].5 g Kollidon CL [1] ....2...................0 g Water ............3 % Dissolution....... add III and press to tablets with low compression force......... 3.2..90...........10...2 % 511 mg 12 mm biplanar 95 N 3 min 0.....4 min Friability .... Tablet properties No........ 2.. 2 Weight ..................................95..............12 mm Form ...496 mg Diameter .............................5 g – 25.....

Formulation Neomycin sulfate .......... add the propylene glycol and dissolve neomycin sulfate............ Yellowish at 45 °C................5....6...5 Lutrol F 127 [1] .....0...........0 Water... Manufacturing Dissolve the parabenes and Lutrol F 127 in water heated to about 80 °C...0 Parabenes ........ BASF Fine Chemicals Generic Drug Formulations 1998 ...74.. Maintain the cool temperature until the air bubbles escaped.0.......... 3.............................7 Formulations of semi-solid drugs (Lab scale) Neomycin Gel (0.........05 Propylene glycol Pharma [1] .. Properties of the gel A clear semisoft gel was obtained................. dissolve Lutrol F 127............... Physical stability (6 weeks) No change at 6 °C and 23 °C........... cool to 5-10 °C................. add propylene glycol and dissolve neomycin sulfate... Alternative: Dissolve parabenes in hot water.... Cool to room temperature when the air bubbles escaped..... 4....5 g g g g g 2...20......05 %) 1....

.............. pass through a 0.....600 mg Diameter .............................................8 % BASF Fine Chemicals Generic Drug Formulations 1998 .........2.....................biplanar Hardness.........76 N Disintegration...............9 Tablet formulations (Lab Scale) Neomycin Tablets (250 mg) 1........................14 min Friability.. 3.....250 Ludipress [1] ...............................................0................... Formulation Neomycin sulfate ...........8 mm-sieve and press to tablets with low compression force..................................................................12 mm Form ......................................334 Magnesium stearate [2] ........................ Tablet properties Weight ..............................................6 Aerosil 200 [4] ......... Manufacturing (Direct compression) Mix all componnents..............10 g g g g 2.............................

...........5 mm sieve..........0 g Ludipress [1] ......................................................2............1........200.............9 Tablet formulations (Lab Scale) Nicotinic Acid (= Niacin) Tablets (200 mg) 1................... Manufacturing (Direct compression) Pass all componts through a 0..............0 g Polyethylene glycol 6000................................................0 g 2............................... mix and press with very low compression force....................................................0 g Magnesium stearate [2] .....0 g Kollidon CL [1] .419 mg Diameter .......................................... 3...............5 g Aerosil 200 [4] ................3...............1 min Friability ...........0........biplanar Hardness.......200................... Tablet properties Weight .. Formulation Nicotinic acid (Lonza)....................5..144 N Disintegration ......................................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........12 mm Form ...................................10................ powder [6]..............

....223 mg Diameter .......................132 N Disintegration ......................................... add IV and press with low to medium compression force..25.............. Tablet properties Weight ...............0 Kollidon CL [1]..0 II.....................20......0 IV........ Microcrystalline Cellulose [5]........... 1982) 1...< 0...................430..... Patent 0078........ Magnesium stearate .....................2............105............10..... Manufacturing (Wet granulation) Dissolve mixture I in II.1% Dissolution (20 min).............9 Tablet formulations (Lab Scale) Nifedipine Tablet Cores (10 mg) (According to Ph........0..................biconvex Hardness ................about 10 min Friability ... Formulation I................................................................... sieve...............4 g g g g g g g 2..........Eur....................................................... Nifedipine................. 3............... Granulate mixture III with solution I/II........ dry the obtained coprecipitate...........90 % BASF Fine Chemicals Generic Drug Formulations 1998 ......................0 Corn starch [3] .......8 mm Form ..40.............. Methylene chloride.180....0 III................................0 Kollidon 25 [1] ..............

............................................ mix and press with low compression force......................0.........................................................26........................ Formulation Nitrendipine.....................6 mm Form .....63 N Disintegration ..................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...... Tablet properties Weight ..........0 Ludipress [1] .0......0 Kollidon CL [1] ..............5 g g g g 2....................5 mm sieve.....9 Tablet formulations (Lab Scale) Nitrendipine Tablets (25 mg) 1..biplanar Hardness.................................2................53................................. 3.................. Manufacturing (Direct compression) Pass all components through a 0.82 mg Diameter ................................................................< 1 min Friability....................1.........5 Magnesium stearate [2]............

..... sieve................8 g Talc [10] ....................................5 g Corn starch [3] ......3 g Magnesium stearate [2] ..... III...2........................... mix with III and press...... Ahmed.................biconvex Disintegration ............. Formulation I....M.....Hosny.......................100 g Corn starch [3] ................. 1631 – 38.................. Kollidon 30 [1] ........................s.......10 g Water.............................. dry........................S.....................A.........180 mg Diameter .......5 min Dissolution (60 min)............ Ind................................................... Pharm 20(9).................... Nitrofurantoin ......................38 g II............. A.8 mm Form . 3.... 1994) 1...78 % (120 min) ...................... Tablet properties Weight ...........1 g 2....93 % BASF Fine Chemicals Generic Drug Formulations 1998 .. Kollidon CL [1] ........................................................... Manufacturing (Wet granulation) Granulate mixture I with solution II.........................20 g Lactose [8] .................q.................................................................9 Tablet formulations (Lab Scale) Nitrofurantoin Tablet Cores (100 mg) (According to E..................... Drug Dev............

.......200 Magnesium stearate [2] .................................................... Tablet properties Weight ..................100 Ludipress [1] ..............2 Aerosil 200 [4] ................1 – 2 min Friability................2.......................................3 g g g g 2.0................................... Formulation Nitrofurantoin ...................................................307 mg Diameter .....12 mm Form ........ pass through a 0.85 N Disintegration............5 % BASF Fine Chemicals Generic Drug Formulations 1998 ..................8 mm sieve and press with low compression force.. 3..........biplanar Hardness................................................................... Manufacturing (Direct compression) Mix all components...........................................................................9 Tablet formulations (Lab Scale) Nitrofurantoin Tablets (100 mg) 1.........

..............0........1 to 0.......... Remarks To prevent of discolouration of Kollidon in the solution during storage 0.......................... Flavours should be added to adjust the required taste..... Merck) Water...........clear solution Taste ..............5 % of cysteine could be added as antioxidant......46...............1 Saccharin sodium........................................ Formulation DL-Norephedrine hydrochloride.......................50................. add the sorbitol. 3.............0.........0............3....... BASF Fine Chemicals Generic Drug Formulations 1998 . Manufacturing Dissolve the parabenes in the hot water.....5........5 Kollidon 90 F [1] ...........................0 Sorbitol solution ...... Properties of the syrup Appearance ...8 Liquid Formulations (Lab scale) Norephedrine Syrup (40 mg/10 g) 1....0 g g g g g g 2................0 (Karion ® F liquid............... cool to room temperature and dissolve the other components..reasonable 4..4 Parabenes (Nipa) .

................................../ml) 1....5.......0.....000 i.....................8 Liquid Formulations (Lab scale) Nystatin Suspension (100..........................5...... Kollidon CL-M....... Properties of the suspension Colour .easy BASF Fine Chemicals Generic Drug Formulations 1998 ........................2..........50 Water .................not observed after one week Redispersibility ......................70 g g g g g g 2......... 3.............. Manufacturing Nystatin................ Kollidon 90 F is added slowly in small portions under vigorous stirring............... Formulation Nystatin ..............yellow Viscosity (25 °C) ...................2..75 Kollidon 90 F [1] ..........................................25 Kollidon CL-M [1]..... sorbitol and citric acid are suspended in water..u............................24.........60 mPa · s Sedimentation ...........00 Sorbitol [10].80 Citric acid .............................64...........

...8 mm sieve.............................. add the components III and press with medium compression force.................. Isopropanol ...14 min Friability ............. dry..........biconvex Hardness.....3 g 2..................51 g II.............. Manufacturing (Wet granulation) Granulate mixture I with the solvent II.......... pass through a 0.....................2..............9 mm Form ........ 3....40 ml III...........200 g Lactose monohydrate [8] ...............................................270 mg Diameter ....................................................................40 N Disintegration....................10 g Magnesium stearate [2] .....9 Tablet formulations (Lab Scale) Nystatin Tabet Cores (200 mg) 1.......................................................................................... Formulation I.................... Tablet properties Weight ............... Nystatin ............... Kollidon CL [1]....................................0 % BASF Fine Chemicals Generic Drug Formulations 1998 ...

...................................175 mg Diameter ............. Tablet properties 50 mg 100 mg Weight ................3 % BASF Fine Chemicals Generic Drug Formulations 1998 .9 Tablet formulations (Lab Scale) Nystatin Tablets (50 mg and 100 mg) 1.........0 2.....................6 % 339 mg 10 mm biplanar 66 N 9 min 0............................8 mm Form ..................... Formulations 50 mg Nystatin ...........10 min Friability ....... pass through a 0.............................0 Ludipress [1]....5 g g g g 2..54 N Disintegration ..................8 mm sieve and press with very low compression force....................0...........................110..........................1....0 Magnesium stearate [2] .........................................55........2............ Manufacturing (Direct compression) Mix the components...1.0 2.. 3.......................................................................................0 Aerosil 200 [4] ...........3 g g g g 100 mg 110...........................................biplanar Hardness .......0 220.........

........................................2............................ This fish oil consists of about 30 % EPA+DHA.......0 Kollidon VA 64 [1] .......................... – These tablet cores could be coated with an enteric coating of Kollicoat MAE 30 D [1] (see chapter 3)......2................................. BASF Fine Chemicals Generic Drug Formulations 1998 .......8................... 3.............................0 Avicel PH 101 [5] ..biconvex Hardness ....................... Manufacturing (Direct compression) Pass all components through a 0.......71 N Friability ..........8 mm sieve.9 mm Form ... Remarks – The dry powder Omega Fatty Acids Dry N-3 contains 25 % fish oil................289 mg Diameter ......140.................< 0...4 Magnesium stearate [2].. Tablet properties Weight .......140........9 Tablet formulations (Lab Scale) Omega Fatty Acids Tablet Cores (10 mg EPA + DHA) 1......15 4..................................................0 g g g g 2........ mix and press with high compression force.... Formulation Omega Fatty Acids Dry N-3 (BASF).....

..8 2... 4....5 g (e..... The reducing agent must be selected in accordance with the legislation of the corresponding country.....7 g Kollidon 17 PF [1] ..5.g.. Adjust the pH with IV.. Manufacturing Suspend III in solution II................ The function of Kollidon 17 PF not only is the solubilisation of oxytetracycline but also the reduction of its local toxicity. BASF Fine Chemicals Generic Drug Formulations 1998 . Rongalite® C..............46 g IV. Remarks The absence of oxygen during manufacturing and in the final packaging and a good quality of oxytetracycline HCl are essential to avoid the oxidation (= dark solution).....ad 100 ml III.........0 g Reducing agent .............. Formulation I................. Ethanolamine . Magnesium oxide ....10....8 Liquid Formulations (Lab scale) Oxytetracycline Injectable Solution for Veterinary Application (500 mg/10 ml) 1....0.. pass continously nitrogen through the solution to avoid oxidation and add slowly I to the well stirred solution........................5...... Properties of the solution Yellow clear solution.... II...to adjust pH 8....... Oxytetracycline hydrochloride ............................. BASF) Water for injectables .. 3.....0........

.......... Heat the solution to 75 °C..........00 g Sodium formaldehyde sulfoxylate ...... Manufacturing Mix the water and the Soluphor P....84 g Water of injectables....... sodium formaldehyde sulfoxylate (Rongalite‚ C..... slowly stir in the oxytetracycline until a clear solution is obtained.. After the solution has cooled......018........s...... Add the sodium formaldehyde sulfoxylate and stir until dissolved..889 (1976) 1.........g....00 ml 2.......8 Liquid Formulations (Lab scale) Oxytetracycline Sustained Release Injectable for Veterinary Application (2........ The reducing agent e..00 g Kollidon 17 PF [1] .... Formulation Oxytetracycline...92 g Soluphor P [1] .22.......40. After the magnesium oxide has been suspended......................5... BASF Fine Chemicals Generic Drug Formulations 1998 ........ 3..5....... and dissolve the Kollidon 17 PF in the mixture.............q.... ad 100.44 g 2-Aminoethanol .0...................... Remarks The quality of the oxytetracycline and the complete absence of oxygen during the manufacturing and packaging of the solution is essential to obtain a acceptable chemical stability and no dark colour........1....5 with aminoethanol..............3..... BASF) must be selected in accordance with the legislation of the corresponding country.2 g/10 ml) (According to US-Patent 4..... set to pH 8....65 g Magnesium oxide ......

...........................................................................495 mg Diameter ...................................8 mm sieve and press with very low compression force.... 3...........250 g Ludipress [1] .....................12 mm Form .......................2....86 N Disintegration ..................................................biplanar Hardness...6 g 2...........1% BASF Fine Chemicals Generic Drug Formulations 1998 .................. Formulation Oxytetracycline hydrochloride .4 min Friability .................... Manufacturing (Direct compression) Mix all components...................................9 Tablet formulations (Lab Scale) Oxytetracycline Tablets (250 mg) 1.......................0........................................230 g Magnesium stearate [2] .... pass through a 0......... Tablet properties Weight ....

..........................................2.......... pass through a 0............9 Tablet formulations (Lab Scale) Pancreatin Tablet Cores (30 mg) 1..................................308 Kollidon CL [1]..4 – 5 min Friability .......< 0................................................................. Enteric coating See Chapter 3...........................10 Magnesium stearate [2] .............. Tablet properties Weight .............................. Manufacturing (Direct compression) Mix the components................ Formulation Pancreatin (Knoll) ............2 g g g g 2.......1% 4................355 mg Diameter ........................ 3.............76 N Disintegration ........................8 mm sieve and press with low compression force..... BASF Fine Chemicals Generic Drug Formulations 1998 .....30 Ludipress [1] .........8 mm Form ....................................biconvex Hardness.......................................

.....................2...................... BASF Fine Chemicals Generic Drug Formulations 1998 .........................................3 g g g g g g 2.................................2 Aerosil 200 [4] ...............................................177 N Friability ....biconvex Hardness .....< 0................................................................................ Manufacturing (Direct compression) Mix the components and press with high compression force......324 mg Diameter .......9 Tablet formulations (Lab Scale) Pancreatin Tablet Cores (130 mg) 1.............................127 Lactose monohydrate [8] .........................130 Cholic acid............................ Formulation Pancreatin (Knoll)....................2 Avicel PH 101 [5] ...............................56 Magnesium stearate (Merck) ......................1% 4...................9 mm Form .... 3.... Enteric coating See Chapter 3.... Properties of the cores Weight .....................

.......................... 3.................................biconvex Hardness...........................11mm Form .........................................290 Kollidon CL [1] .........615 mg Diameter .....25 Magnesium stearate [2] .........3 g g g g 2... Tablet properties Weight ............ Manufacturing (Direct compression) Mix the components........... pass through a 0.. BASF Fine Chemicals Generic Drug Formulations 1998 ..........9 Tablet formulations (Lab Scale) Pancreatin Tablet Cores (300 mg) 1...................................................................74 N Friability ................................. Enteric coating See Chapter 3................ Formulation Pancreatin (Knoll) .................8 mm sieve and press to tablets with low compression force.............300 Ludipress [1] ......................................2..............1% 4...................< 0...

..................................... 3..............................................................................................90 g Kollidon 30 [1] ...................20 g Polyethylene glycol 6000.........9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) + Caffeine Tablets (500 mg + 50 mg) 1................... Remark If the flowability of the powder mixture for tabletting is not high enough some Aerosil 200 [4] should be added...10 g 2................................................. Manufacturing (Direct compression) Mix all components.......10 g Kollidon CL [2] .............12 mm Form ........56 N Disintegration ... 15 min .....................................683 mg Diameter ..500 g Caffeine (Knoll) ...................... Formulation Paracetamol.................< 1 min Friability.............................. Tablet properties Weight ...........................91% 4....... BASF Fine Chemicals Generic Drug Formulations 1998 ..............0..............8 mm and press with high compression force.............................2......................... pass through a sieve of 0......... powder [6] .................biplanar Hardness.50 g Avicel PH 101 [5] ......... crystalline ..9 % Dissolution.................

.....1 g) 1.4.............................1 g in sachets at maximum 30 % of relative atmospheric humidity.... Paracetamol........................30 g Sugar ... Sodium citrate. Remark If the solvent insopropanol is replaced by water the granulation should be done in a fluidized bed.................................................500 g Doxylamine succinate .. Manufacturing Granulate mixture I with solution II........417 g II.... powder....... BASF Fine Chemicals Generic Drug Formulations 1998 ...5 g Caffeine (Knoll) ........4 Formulation of granules...33 g Tartaric acid .............s........................... Formulation I.391 g Sodium hydrogen carbonate .......................707 g 2.... dry at 60°C under vacuum conditions.............. Fill 2. III. dry syrups and Iyophylisates (Lab scale) Paracetamol (= Acetaminophen) + Doxylamine + Caffeine Effervescent Granules (500 mg + 5 mg + 33 mg/2. Properties Free flowing granules............................................ sieve and mix with III......... Kollidon 30 [1] ..... 4.............................................................. 3.q....6 g Isopropanol (or Ethanol) ..

......................– Kollidon 30 [1] ...........5 g 500 mg paracetamol) in a glass of Formulation No................. or 2.............. Manufacturing (Wet granulation) Granulate mixture I with solution II....... Administration Formulation No.0 g of the granules (= 250 mg or water....................12 g Kollidon 90 F [1] .– Citric acid ....................0 g in sachets. 4......– Ethanol 96 %. Formulation No.....4.. 3.....– Kollidon CL-M [1] ............................ and pass through a 0......................... 2: Fill 1...................................... Formulations I.90 g Aspartame .................. 1 No.... 2: Suspend 1............ BASF Fine Chemicals Generic Drug Formulations 1998 ...75 g 50 g – 130 g 50 g 7g 5g 5g 3g 3g – 8g 50 g 2...4 Formulation of granules...... 1: Fill 1..................3 g or 2................................. Properties of the granules The free flowing granules are very well dispersible in cold water..................................... dry syrups and Iyophylisates (Lab scale) Paracetamol (= Acetaminophen) Instant Granules (250 mg or 500 mg) 1.........................5 g Sodium citrate ..................7 g Orange flavour .. 2 Paracetamol...........................5 g Strawberry flavour .........5 g or 3......... fine powder.............128 g Sorbitol Instant (Merck)... fine powder ..........6 g in sachets.50 g Sucrose........ Formulation No............ II....................3 g 500 mg paracetamol) in a glass of or 3...... No.............................................6 g of the granules (= 250 mg or water.. 1: Suspend 1................8 mm sieve.....

No sedimentation within two hours. BASF Fine Chemicals Generic Drug Formulations 1998 .5. milky appearance with a sweet and fruity taste. Properties of the suspensions Yellowish. 6. Chemical stability of the granules (Formulation No. 1) No loss of paracetamol after 2 months at 60 °C.

......5 mm sieve..............................................................................2..................5 g Aerosil 200 [4] ....................200 g Magnesium stearate [2] .....12 mm Form ...............................................................761 mg Diameter ........................9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) + Ibuprofen + Orphenadin Tablets (250 mg + 200 mg + 100 mg) 1.......biplanar Hardness..........0....250 g Ibuprofen .........................................100 g Ludipress [1] .................... Manufacturing (Direct compression) Pass all components through a 0.......74 N Disintegration ...........................................200 g Orphenadine hydrochloride ...............................................6 min Friability......... Tablet properties Weight .......5 g 2.... Formulation Paracetamol........ 3......... mix and press with high compression force......7 % BASF Fine Chemicals Generic Drug Formulations 1998 .......................................................... powder < 300 µm ..........

.........................2............................. Kollidon 30 [1] ...........................12 mm Form .....s........8 mm sieve.... Paracetamol............................................. Formulation I..................97 N Disintegration......5 g 2...............................25 g Ethanol 96 % ...........1 – 2 min Friability..7 % BASF Fine Chemicals Generic Drug Formulations 1998 ............................................25 g Phenyltoloxamine ................biplanar Hardness....... Tablet properties Weight ...........25 g Magnesium stearate [2] .............. 3...................................0....9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) + Norephedrine + Phenyltoloxamine Tablets (300 mg + 25 mg + 22 mg) 1...........................................300 g Norephedrine hydrochloride (Knoll) .................22 g Corn starch [3] .............................200 g II..... III................ pass through a 0....601 mg Diameter ....... add III and press with high compression force............................. dry.........q........................................... Kollidon CL [1] ....... Manufacturing (Wet formulation) Granulate mixture I with solution II.......... crystalline (Merck) ..........

.........................................200 g Phenprobamat .............q...200 g Avicel PH 101 [5] .....35 g Kollidon VA 64 [1] .......................................8 % BASF Fine Chemicals Generic Drug Formulations 1998 .......................... Tablet properties Weight ...............12 mm Form ................................54 N Disintegration ........................ 3......2.........5 mm ....... Formulation Paracetamol......... mix and press with high compression force..........................5 g Aerosil 200 [4] ...............................10 g Magnesium stearate [2] .................................................................. 2..465 mg Diameter ........................................... Manufacturing (Direct compression) Pass all components through a 0........9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) + Phenprobamat Tablets (200 mg + 200 mg) 1...biplanar Hardness.... powder < 0......20 g Kollidon CL [1].......................................................8 mm sieve....< 1 min Friability........................0..............................................s...

...................................................... Formulation I..........2........ BASF Fine Chemicals Generic Drug Formulations 1998 ......30 Strawberry flavour (FDO) .......... II.......................... milled (Hoechst) ................. pass through a sieve and press with medium compression force................60 Ethanol 96 % ........300 Sucrose........................................................................................620 mg Diameter .20 mm Form .........................biplanar Hardness .........................about 425 g g g g g g g 2.1.............................. Taste on chewing of the tablets Sweet........................27 min Friability........30 Kollidon 30 [1] ............ Manufacturing (Wet granulation) Granulate mixture I with solution II.............................111 N Disintegration ................ 3.................9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) Chewable Tablets (300 mg) 1. milled.....600 Kollidon CL-M [1].........................1% 4........................ Paracetamol......550 Orange flavour (FDO) ......... Tablet properties Weight ........................... fruity and only very slightly bitter.....

...........4 min Friability........................biplanar Hardness .................................. powder < 300 µm ............... pass through a 0...............................8 mm sieve. Kollidon 30 [1] ...2.. Polyethylene glycol 6000.........................100 ml III..430 g Dextrose ............................... Formulation I...500 g Tartaric acid................... 3. powder [6]......... Paracetamol.................9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) Effervescent Tablets (500 mg) 1........................... mix and press to tablets.. powder ..............700 mg Diameter ............................150 N Disintegration ............... add III....................1................ Manufacturing (Wet formulation) Granulate the mixture I with solution II................0................................................................200 g Flavouring II.................................16 mm Form ...60 g 2..... Tablet properties Weight ..............20 g Isopropanol ............500 g Sodium bicarbonate ...........7 % BASF Fine Chemicals Generic Drug Formulations 1998 ..................

.. Formulation I..................... Fill 2............50 g g g g g g g 2... Paracetamol................... powder ........44 g in a glass water)................. dry syrups and Iyophylisates (Lab scale) Paracetamol (= Acetaminophen) Instant Granules (500 mg) 1............8 Ethanol 96 % ....50 Citric acid...... Manufacturing (Wet granulation) Granulate mixture I with solution II and dry.... Properties of the suspended granules The taste of the suspension is only slightly bitter (2...................... II.............3 Sodium citrate............................ No sedimentation can be observed during some minutes........... fine powder .......44 g in sachets (= 500 mg Paracetamol).......... 3................. Properties of the granules The free flowing granules are very well dispersible in cold water.............130 Lutrol F 127 [1] .3 Kollidon 90 F [1] .......... BASF Fine Chemicals Generic Drug Formulations 1998 ..............50 Sorbitol instant (Merck) ......4 Formulation of granules........... 4....4.........

...0 g Solubility in water ................... 2 500 mg Paracetamol......... Fill the molten mass in the moulds of suppositories....... fine powder ...............0...0 g – 10.......................................... 1 150 mg No....4 g 50....colourless 4.0 g 80............0 g 2..................................... Physical stability (Formulation No................. Formulations I......................... No......6....2........... Properties of the suppositories Weight ................. 20 °C or 40 °C............... 1) No crystallisation after the storage of 6 weeks at 6 °C.........– Lutrol E 1500 [1] .....7 Formulations of semi-solid drugs (Lab scale) Paracetamol (= Acetaminophen) Suppositories (150 mg and 500 mg) 1...15.. BASF Fine Chemicals Generic Drug Formulations 1998 .....0 g Lutrol E 4000 [1]............................................easy Colour ... Manufacturing Melt the mixture II and suspend the mixture I... 3..55........2 g Lutrol E 400 [1] .....................129..0 g 60........4 g Aerosil 200 [4] .. II..

.58.......... Kollidon CL-M and paracetamol.0....0 Citric acid...........0 Orange flavour........... stable suspension showing almost no sedimentation during 24 hours and good redispersibility (easily to homogenize by shaking twice to 3 times)...8 Liquid Formulations (Lab scale) Paracetamol (= Acetaminophen) Suspension (5 % = 500 mg/10 ml) 1......... Properties of the suspension Practically tasteless..................1 Dextrose ........5 Sodium citrate......30.. BASF Fine Chemicals Generic Drug Formulations 1998 .........0..5 Kollidon CL-M [1] ... homogeneous suspension is obtained.................5.................0..................................................................... 3....... Formulation Paracetamol............. powder ........... Manufacturing Prepare the solution of dextrose in water and add the other solid ingredients with stirring in the following sequence: citric acid.............. sodium citrate...5..... powder ......9 g g g g g g g 2........ orange flavour................. A white..5..................0 Water.....

......2 to 0............................. 3....... 4....0 Cyclamate sodium.....20.0 Sorbitol.......................................0 Water.5.0 1. BASF Fine Chemicals Generic Drug Formulations 1998 ...... Manufacturing Dissolve first Kollidon 25 and then the other solid components in the solvent mixture of glycerol.0 Strawberry flavour ...............0 Glycerol ..31.2-Propylene glycol Pharma [1] .... To prevent of discolouration during storage 0......................5.. Properties of the syrup Clear solution of certain viscosity having only a slightly bitter taste.................1 Kollidon 25 [1] ......... propylene glycol and water..20........ crystalline [10]........... The colour of the solution changed only a little during 3 months at 25 °C and 40 °C........0.... Chemical stability (HPLC) No loss of paracetamol was found during 3 months at 40 °C................................................. Formulation Paracetamol (Merck).......15......................4.....5 % of cysteine could be added as antioxidant.....5......0 g g g g g g g g 2.8 Liquid Formulations (Lab scale) Paracetamol (= Acetaminophen) Syrup (5 % = 500 mg/10 g) 1........... Physical stability The solution remained clear during more than 1 week at 6 °C and during more than 3 months at 25 °C and 40 °C.. 5..

..............................5........... Dissolve the flavours and mix with glycerol......< 0.. crystalline ......... Properties of the syrup The obtained syrup is a viscous... BASF Fine Chemicals Generic Drug Formulations 1998 ............... Manufacturing Dissolve Kollidon in water. clear sweet and only slightly bitter liquid..............................6...........0..........5 % = 250 mg/10 ml) 1...... add paracetamol and cyclamate...5 g 2...............0 g Orange flavour ....................30...........57.0 g Glycerol ............... 3....... heat to 50 °C and stir to obtain a clear solution....................2 g Water ...........8 Liquid Formulations (Lab scale) Paracetamol (= Acetaminophen) Syrup for Children (2....5 g Kollidon 25 or Kollidon 30 [1] ................2.1 g Raspberry flavour ........0 g Sodium cyclamate ...4...... Formulation Paracetamol.......

........ sieve and mix with III.........30 g Kollidon CL [1]....... 70 g III................................................ Tablet properties Weight .............12 g Polyethylene glycol................< 1 min Friability . Formulation I.....................88 % 30 min ...........10 g 2.......... Kollidon CL [1]....................... powder [6] .........< 0...9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) Tablet Cores (500 mg) 1......97 % BASF Fine Chemicals Generic Drug Formulations 1998 ..... Paracetamol.......................................................................... Kollidon 90 F [1] ............ 10 min................ Press with high compression force of 25 – 30 kN......500 g Dicalcium phosphate [9] ......... Manufacturing (Wet granulation) Granulate mixture I with solution II.2..........................................................157 N Disintegration ...............20 g II............ dry...................... powder (RPR) .......................................................................1% Dissolution...........12 g Kollidon VA 64 [1] ...10 g Ethanol 96 %.....................11 mm Form ....max....587 mg Diameter ......biconvex Hardness ............................................................................................. 3.........

................. 10 min ......................................500 g (Synopharm) Avicel PH 102 [5] ................................................. pass through a 0.........84 % 30 min .............................................12 mm Form ........................................... 3... 1 No. Tablet properties No.............. 2 Paracetamol...0................................60 N Disintegration .......... add the lubricant and press with high compression force of 25 – 30 kN.................... 1 No.............. powder [6] .............3 g Polyethylene glycol 6000.....35 g Kollidon CL [1] ............................................................ mix all other components........................ crystalline .8 mm sieve................................. 2 Weight .............4 % 73 % 86 % BASF Fine Chemicals Generic Drug Formulations 1998 .............7 % Dissolution....................6 min Friability ...........................2................biplanar Hardness ...........................9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) Tablets (500 mg) 1................. Formulations No.....98 % 703 mg 12 mm biplanar 87 N 1 min 0.......21 g Magnesium stearate [2] ...............– Aerosil 200 [4] ...137 g Kollidon VA 64 [1] ......699 mg Diameter .......4 g 500 g 150 g 20 g 15 g – 15 g 2g 2......... Manufacturing (Direct compression) Pass the lubricant through a 200 µm sieve..........

......... Manufacturing (Direct compression) Pass all components through a 0..........168 Kollidon VA 64 [1] .....................4 % BASF Fine Chemicals Generic Drug Formulations 1998 .....2 g g g g g 2..... 3......................................2...........................401 mg Diameter ..............................................210 Avicel PH 101 [5] ..6 Magnesium stearate [2] ........................... Merck) .............................biplanar Hardness.... Tablet properties Weight ....... mix and press with medium compression force...... Formulation Paracetamol (= Acetaminophen......0............................9 Tablet formulations (Lab Scale) Paracetamol (= Acetaminophen) Tablets for Children (200 mg) 1................................................................8 mm sieve..............................................................12 mm Form ...............65 N Disintegration ..< 1 min Friability...............................13 Kollidon CL [1] ........

.......................... 3.......................... mix and press with medium compression force.................................................281 Magnesium stearate [2] ....................................9 Tablet formulations (Lab Scale) Phendimetrazin Tablets (35 mg) 1.......................... BASF Fine Chemicals Generic Drug Formulations 1998 .................biplanar Hardness .......0.................. Remark The amount of Ludipress and/or corn starch could be reduced..................................2.....................8 mm sieve........> 3 g g g g g 2.........12 mm Form ............3 – 4 min Friability...... Formulation Phendimetrazin ..................281 Corn starch [3] ....2 % 4...35 Ludipress [1] .........146 N Disintegration (water)....................604 mg Diameter ............ Manufacturing (Direct compression) Pass all components through a 0........................................... Tablet properties Weight ....................................> 3 Aerosil 200 [4] .......................................

..........................................8 mm sieve and press with low compression force.............230 mg Diameter ..................................... pass through a 0...................................0.biplanar Hardness ................2.... Formulation Phenindion...................................50 g Ludipress [1] .. Manufacturing (Direct compression) Mix all components.....1% BASF Fine Chemicals Generic Drug Formulations 1998 ............2 g 2............................................................. 3.........................15 min Friability ..........193 N Disintegration..... Tablet properties Weight ..................................................9 Tablet formulations (Lab Scale) Phenindion Tablets (50 mg) 1...........................165 g Magnesium stearate [2] ................................8 mm Form ........

................................19 g Magnesium stearate [2] .......9 Tablet formulations (Lab Scale) Phenolphthalein Tablet Cores (200 mg) 1............................................ 3..................385 mg Diameter ... Formulation I.......< 1 min Friability..... Manufacturing (Wet granulation) Granulate mixture I with solution II. s........................8 sieve and press with low compression force................280 N Disintegration (water) ....................................q... Kollidon 30 [1] ......0.........3 g 2..................................................................................... mix with III..................... III.....................9 mm Form . Phenolphthalein..........................150 g II......................... pass through a 0............biconvex Hardness.....2............... Kollidon CL [1]........ Tablet properties Weight ........2 % BASF Fine Chemicals Generic Drug Formulations 1998 .......11 g Isopropanol or ethanol 96 % ..............................200 g Dibasic calcium phosphate [9] .............

..........................q........................... Manufacturing Dissolve the preservative and Kollidon 90 F in water and suspend Kollidon CL-M and phenytoin............. Content uniformity of phenytoin in the suspension mg Phenytoin/ml after 1 h after 24 h 60 50 40 30 20 10 0 low area medium area Fractions of the suspension high area BASF Fine Chemicals Generic Drug Formulations 1998 ..................................5... Formulation Phenytoin ......................................86 g 2....8 g Kollidon 90 F [1] ................ Water..................5 g Kollidon CL-M [1] ..8 Liquid Formulations (Lab scale) Phenytoin Oral Suspension (5 %) 1......... 3......1 g Preservative .......s.........................................

.......................................................2 % Dissolution.......9 Tablet formulations (Lab Scale) Phenytoin Sodium Tablets (100 mg)......................................................... pass through a 0........................... Manufacturing (Direct compression) Mix all components.............................12 mm Form .9 min Friability.........................346 mg Diameter ...................100 Ludipress [1] ......................5 g g g g g 2.82 N Disintegration ............. Tablet properties Weight .....................................10 Kollidon CL [1] .............biplanar Hardness.......................57 % 30 min ........... 3.......................2.... Formulation Phenytoin sodium (Sigma) ..8 mm sieve and press with low compression force............................................89 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........8 Aerosil 200 [4] ...... 10 min...........235 Magnesium stearate [2]..................................................... DC 1.............................................0...................

.................................biplanar Hardness.. WG 1.................45 II................................................................................5 % BASF Fine Chemicals Generic Drug Formulations 1998 ............ mix with III and press with high compression force.......................................8 mm sieve............. 3.......................100 Dicalcium phosphate [9] ...........................................60 N Disintegration .............. dry........0................50 Sucrose...........................10 Isopropanol + Ethanol (1 + 1) . Formulation I............................. crystalline .....................5 Magnesium stearate [2] .... Kollidon 25 [1] ...........209 mg Diameter ...........2 g g g g g g g 2.........9 Tablet formulations (Lab Scale) Phenytoin Sodium Tablets (100 mg)......................................30 III.... pass through a 0....8 mm Form ....................... Tablet properties Weight ..... Phenytoin sodium .........................3 min Friability......2.................... Kollidon CL [1] ..... Manufacturing (Wet granulation) Granulate mixture I with solution II...

....9 Tablet formulations (Lab Scale) Phenytoin Tablets (100 mg) 1............ pass through a 0........... Tablet properties Weight .................biplanar Hardness....2 Stearic acid [7] ...................8 mm sieve and press with low compression force.........................................351 mg Diameter ..........................................100 Ludipress [1] .....5 g g g g g g 2......8 Aerosil 200 [4] .........2...........................4 % BASF Fine Chemicals Generic Drug Formulations 1998 ........................................235 Magnesium stearate [2] ................... 3..............1 min Friability......................................................12 mm Form ... Manufacturing (Direct compression) Mix all components..................................... Formulation Phenytoin base (Fluka) ...................................81 N Disintegration .....0.....................................................2 Kollidon CL [1] ..............................................................................

......6... adjust the pH with triethanolamine to about 7................... Stirr the highly viscous mixture.... Manufacturing First mode of preparation: Prepare the solution of piroxicam in propylene glycol and dexpanthenol at 70 – 80°C..25.........23.. cool to room temperature when the air bubbles escaped and adjust the pH to about 8.............. dexpanthenol and triethanolamine.........5 1...0 g g g g g g g 2.about 0.......... Alternative mode of preparation: Dissolve piroxicam in propylene glycol......... 3...............5.........0 Ethanol 96 % ....0 Water...0 Dexpanthenol (BASF)...................... BASF Fine Chemicals Generic Drug Formulations 1998 ..5 % + 5..... Maintain the cool temperature until the air bubbles escaped..............0 %) 1................. Formulation Piroxicam (Sigma)....... Remark The addition of ethanol is not essential because it reduces the viscosity.....0 Triethanolamine.............7 Formulations of semi-solid drugs (Lab scale) Piroxicam + Dexpanthenol Gel (0............ add 50 % of the hot water (70°C).......... Add the ethanol..... Cool the mixture of Lutrol F 127 and water to about 5 °C and mix with the piroxicam solution.. add ethanol and Lutrol F 127....... Properties of the gel A clear colourless gel was formed having a pH of about 8.......5.46..2-Propylene glycol Pharma [1] ........ 4...... add the rest of the water....0.......4 Lutrol F 127 [1] ..

...57 sec Friability ...............150 g Ludipress [1] ............ pass through a 0....50 g Kollidon CL [1] .............................10 g Aerosil 200 [4] ................................... Tablet properties Weight ...................................................................... Formulation Piroxicam................... Manufacturing (Direct compression) Mix all components...........................................biplanar Hardness............................66 N Disintegration (water)................1 – 2 g 2.........8 mm Form ..............................................................8 g Polyethylene glycol 6000 powder [6] .238 mg Diameter .......8 mm sieve and press with low to medium compression force...........2.............................................9 Tablet formulations (Lab Scale) Piroxicam Water Dispersible Tablets (20 mg) 1...............................0........................ 3.......1% BASF Fine Chemicals Generic Drug Formulations 1998 .............20 g Corn starch [3] ...................................

.1% 2.05 % 15 kN 110 N 2 – 3 min < 0.......9 % Magnesium stearate [2] ......9 Tablet formulations (Lab Scale) Placebo Tablets 1.....99..2.......05 % BASF Fine Chemicals Generic Drug Formulations 1998 .......................... Influence of the compression force on the tablet properties (300 mg tablet weight) compression force Property Hardness Disintegration Friability 7 kN 45 N 1 min 0......... sieve and press...05 % 22 kN 160 N 3 – 4 min < 0.... Manufacturing (Direct compression) Mix the components..0. 3....... Formulation Ludipress [1].

.............135 Isopropanol............8 Liquid Formulations (Lab scale) Polidocanol Wound Spray (0.....1 Kollidon VA 64 [1] . Manufacturing of the spray Fill the solution into spray cans with the necessary quantity of propellant (e.. g..................................... BASF Fine Chemicals Generic Drug Formulations 1998 .............................. Polidocanol ...............40 g g g g g g 2...10 Ethocel ® 20 (Dow) ......... Manufacturing of the solution Dissolve the components I in the solvent mixture II......... Formulation I.....5.............................................. propane/butane) or in a mechanical pump bottle. 3.............4 Ethyl acetate ..............10 Lutrol E 400 [1] ............... II....................5 %) 1...................

..................1........1.0 III...s pH value (20 % in water) ....5 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............0 Sodium chloride ....000 mPa............. Lutrol F 127 [1] .....................6......... Manufacturing Dissolve the solids (I) in water (IV).7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine + Lidocain Gel (10 %) 1......... cool to about 6 °C..............9 IV............ 23 °C)........61.7..........2........................0 Lidocain hydrochloride........ PVP-Iodine 30/06 (BASF) ......4... Maintain the cool temperature until the air bubbles escaped..... 52 °C) Viscosity (Brookfield...000 mPa · s pH value (20 % in water) ....0 II........10....54.......7 4......51........ 1 molar .... dissolve Lutrol F 127 (II) and adjust the pH value with the sodium hydroxide solution (III).. 3......................... Water ........... Sodium hydroxide solution.4 Loss of available iodine.. 23 °C) . Formulation I.15.......20.......................1 g g g g g g 2.......... Properties of the gels Viscosity (Brookfield..... Stability (14 days.

......... Cut the bar in pieces on a Lab stamper.................... Give the blend 3 times through a plodder with a narrow sieve hole disk.................... Pass the blend 4 x through a three-roller mill......... Manufacturing Dissolve PVP-Iodine in water........ Heat the area of the 2 disks is to 50 °C by a heating collar..75 Syndet base (see Remark) ........................................ 3......... Remark Composition of the syndet base (sequence of concentration): Disodium lauryl sulfosuccinate Sodium lauryl Sulfate Cetylstearyl alcohol Paraffin Glycerol stearate Water Titanium dioxide BASF Fine Chemicals Generic Drug Formulations 1998 .........10 Water... mix the solution with the fragrance and the syndet base......50 Fragance............. Pass the blended material through a wide sieve hole disk combined with a mouth hole disk.940 g g g g 2...6........ Formulation PVP-Iodine 30/06 (BASF) .....7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Bar Soap (5 %) 1....

......0 g Paraffin (56 – 58 °C) ...... 2 PVP-Iodine 30/06 (BASF) ...............2 – g g g g 2.3 45..5 % BASF Fine Chemicals Generic Drug Formulations 1998 .......48......0 g Texapon ® K 12 (Henkel) ....1% 11...... Cut the bar in pieces on a Lab stamper..9.................0 g 48..............................................................– Cetylstearyl alcohol ....................6... Pass the blend four times through a three-roller mill and let dry over night at room temperature. Add solution I and let cool to room temperature continuously stirring..........3 g Emcol ® 4400............7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Bar Soaps (5 %) 1............................3 g 48.3 29.29..................2 g 10..............0 19..19.. Formulations I........ Chemical stability (40 °C during 4 weeks) No..48.... 3..........0 g 15..45........3 g Glycerol monostearate...... 2 Loss of available iodine .....10.. II... No...3 g Setacin ® F special paste (Zschimmer + Schwarz) ....1 (Wilco)...............0 g Water...... Manufacturing Heat mixture II to 75 – 80 °C and cool to about 50 °C well stirring.......15........... 1 No................ 1 No....

......................0 g Texapon ® K 12 (Henkel) . diluted .. Properties of the solutions Brown transparent liquids having a pH of about 1.... 4.7... Manufacturing Dissolve the surfactant II in solution III and add slowly PVP-Iodine I.............20....... II.5..... 3....3 g 4....ad 100 g 20............................3 g 10............5.................................................10..............3 g Ethanol 96 % ........ 2.............– Cremophor NP 14 [1]...0 g 5...8 Liquid Formulations (Lab scale) Povidone-Iodine Concentrates for Broilers and Cattles (20 %) 1....3 g Sulfuric acid.............. BASF Fine Chemicals Generic Drug Formulations 1998 ............. 1 No. Administration as preventive desinfectant Dilute about 3 ml of the concentrate with 1 l of water.................0 g ad 100 g I............ Formulations No...... Tartaric acid ............0 g III.............. 2 PVP-Iodine 30/06 (BASF)....0 g Water ...........0 g – 7...........4...

..6..... Manufacturing Prepare a basic cream from the emulsifying agents and the fatty substances (II)....... Stir in the PVP-iodine dissolved in the buffer solutions (I).. 3.....................0 Cetylstearyl alcohol.2......0 Liquid paraffin........... Chemical stability pH Available iodine Loss of iodine After production After 14 days/52 °C 4...............0 Citric acid solution 0.......2 molar..1 0.10.........09 % – 4...... PVP-Iodine 30/06 (BASF) ....5 1..2 % During this stress test at 52 °C the emulsion was separated into two phases...5...................... Formulation I.0 g g g g g g g g 2.2.............10.1 Na 2HPO 4 solution 0........24..........9 Cremophor A 6 [1] .........10..... 4....99 % 9................... II....5......1 molar .36.0 Cremophor A 25 [1] ........ Properties of the cream Brown cream having a pH of 4............. BASF Fine Chemicals Generic Drug Formulations 1998 ...........................................0 Glycerol ........7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Cream (10 %) 1.....

.......................1... Manufacturing (Direct compression) Dry the mixture II for 4 hours at 60 °C............ mix with I and III and press to tablets........................ BASF Fine Chemicals Generic Drug Formulations 1998 .......................9 % 4.............................................360 Ludipress [1]....2............. PVP-Iodine 30/06 M 10 (BASF) .................................biplanar Hardness....................................360 Sodium bicarbonate......265 III........0..................................................................2.......................2 mg mg mg mg mg mg mg 2............. Tablet properties Weight .......... II........450 Tartaric acid .............2 Aerosil 200 [4] .............5 g Diameter ..........7 min Friability. Application The tablet is dissolved in water to obtain a vaginal douche solution....................................19 Calcium arachinate [2] ......... Talc [10] ................... 3............9 Tablet formulations (Lab Scale) Povidone-Iodine Effervescent Vaginal Tablets (350 mg) 1...........20 mm Form ......... Formulation I................200 N Disintegration in water........................................

......................0.. BASF Fine Chemicals Generic Drug Formulations 1998 .......01 g Water .........5.............0 g Cremophor A 25 [1] .8 Liquid Formulations (Lab scale) Povidone-Iodine Foam Spray (10 %) 1................. Manufacturing Dissolve PVP-Iodine in the solution of Cremophor A 25 in water.......... 3..... Fill the aerosol cans with 90 parts of this solution and 10 parts of propane + butane (1+3).ad 100 g 2. Chemical stability (14 days.. 52 °C) The content of available iodine dropped to 98 %. Formulation PVP-Iodine 30/06 (BASF) ..............10...........

.............80.........1... Formulation PVP-Iodine 30/06 (BASF) .......................8 Liquid Formulations (Lab scale) Povidone-Iodine Gargle Solution Concentrate (10 %) 1... BASF Fine Chemicals Generic Drug Formulations 1998 ............5..............0 Propylene glycol Pharma [1] .... Properties of the concentrate Brown transparent liquid.....0 Water.............. 3.......10........0 g g g g 2.... Administration Dilute 10 ml of the concentrate with about 100 ml of water........ 4..............9..... Manufacturing Dissolve the PVP-Iodine in the solvent mixture.0 Ethanol 96 % .........

...........7. Lutrol F 127......... Maintain cool until all air bubbles disappeared.... Cool to 5 – 8 °C and dissolve V.....99 % 1% 124.........0 IV.4 1...........7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Gel-Cream (10 %) 1.......000 mPa · s BASF Fine Chemicals Generic Drug Formulations 1998 ....... PVP-Iodine 30/06 (BASF) . II.........0 Citric acid solution.6........1 Lutrol E 400 [1]........0 % – 113............. 4.....2 molar .. Properties Brown turib gel...........5.18.... Manufacturing Dissolve I in solution II.... mix with III and dissolve IV at about 20 °C... Lutrol F 127.15....0 V.35... Chemical stability (20–25 °C) pH Available iodine Loss of iodine Viscosity (Brookfield) 0 Months 3 Months 6 Months 3...0 g g g g g g g 2......95 % 5% 122....... Formulation I............9 NA 2HPO 4 · 12H 2O solution................... 3.10.........0 III.10...................1 0............. 0..000 mPa · s 3...1 molar .000 mPa · s 3..1 0.... Liquid paraffin......... 0..

.9 10...... 1 molar.7 8....... dissolve Lutrol F 127 (II) and adjust the pH value with the sodium hydroxide solution (III).......7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Gels (10 %) 1..... cool to about 6 °C...0 % ...6 No....... Stability (14 days.........20. 2 4............0 20. 3.....6..........– IV.. Properties of the gels No.0 1........ 2 61.....0 g Sodium chloride ...000 mPa · s 2.........0 g No. Lutrol F 127 [1] .... 2 10... Sodium hydroxide solution....... 23 °C) pH value (20 % in water) Loss of available iodine BASF Fine Chemicals Generic Drug Formulations 1998 58.0 7....... 1 Viscosity (Brookfield...10. Water....................– II.. Formulations No...000 mPa · s 1..0 g III......... Maintain cool until all air bubbles escaped.. 1 I.70.....000 mPa · s 45.... 23 °C) pH value (20 % in water) No......000 mPa · s 54.........2 % 2... 1 No... 52 °C) Viscosity (Brookfield.. Manufacturing Dissolve the solids (I) in water (IV). PVP-Iodine 30/06 (BASF) ...1 g g g g g 2..2 4.....9 61.....

................................... 3.................... 1987............ PVP-Iodine 30/06 (BASF) . Febr.... APV-Pharmazie in der Praxis No.......84.... Formulation I.. Chemical stability Available iodine Loss of iodine 5...9 Lutrol E 4000 [1]..6. 3... Asanger....................... 4...4 % Remark A similar formulation using sucrose instead of glucose is mentioned in the European Patent 0258761 (Kowa)....... Dolder....5 Glucose [1]........6 Ethanol 96 % .......4.2................0.......4 Glycerol ... Incorporate solution (I) in the obtained paste ........................ Properties of the ointment Brown viscous and turbid paste....291% – 0... 5 – 7) 1.......5 %) (According to R........287 % 1.... II.........0........ M.. Manufacturing Dissolve Lutrol E 4000 in the hot mixture of glycerol and water and add the glucose warmed to 60 – 80 °C........3.....6 Water......... After production After 14 days/52 °C 0.6 g g g g g g 2........ BASF Fine Chemicals Generic Drug Formulations 1998 .....7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Glucose Ointment (2.............

.........7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Lipstick or After Shave Stick (10 %) 1..... When a homogeneous suspension has been obtained cast the sticks in preformed moulds.... PVP-Iodine 30/06 M 10 (BASF)............................................1 g g g g g g g g 2... Properties Brown homogeneous sticks BASF Fine Chemicals Generic Drug Formulations 1998 ....................... Luvitol EHO [1] ................................................ 3......... Formulation I........ stir it into the suspension II and finally add I..............................22 Cetyl alcohol ....... Manufacturing Melt the mixture III at 60°C...6...15 Cremophor RH 40 [1] ........10 White Mineral Oil .23 Solid paraffin (mp..... II.....5 Bees wax .....................18 Sicovit Titanium dioxide [1] ................6 III............................ 50/55 °C) ...........

.............................. Formulations No........................0 g 2.......... 2 PVP-Iodine 30/06 ...0 g Ethanol .........15.... Fill in aerosol cans with propellants like propane+butane or with manual valves. 1 No.10.......5.............8 Liquid Formulations (Lab scale) Povidone-Iodine Liquid Spray (10 %) 1...... BASF Fine Chemicals Generic Drug Formulations 1998 ................0 g Kollidon VA 64 [1] ...................0 g 15........................... 3. Manufacturing Dissolve Kollidon VA 64 in the mixture of solvents and add slowly PVPIodine to the well stirred solution.......0 g – 75....... Chemical Stability The obtained solutions showed no loss of iodine after the storage of 15 days at 60 °C.........– 10...........75.0 g n-Propanol...

.... Manufacturing (Direct compression) Mix all components..........0 g g g g g g g g 2...................................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ..1.....0 Sorbitol...0 – 5......... cryst... crystalline .............................................8 mm sieve an d press with medium compression force.............. sodium ..................0 – 5......................150......0................1.. [10]................1............ potassium ...............2.........8 mm Form ..0 Menthol....9 Tablet formulations (Lab Scale) Povidone-Iodine Lozenges (5 mg) 1.1 Aerosil 200 [4] ............................... crystalline .....................................0 Eucalyptol.............0 Saccharine...............0..........0 Magnesium stearate [2]..biplanar Hardness ............ 3....................> 10 min Friability......................... pass through a 0.....................4.100 N Disintegration in water ...176 mg Diameter .............5..0 Aspartame......4............................................... Tablett properties Weight .. Formulation PVP-Iodine 30/06 M 10 (BASF) ...................

........... II....5 – 8 Cremophor A 6 [1] ....53 – 56 g g g g g g g g 2.................... Formulation I...7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Mastitis Cream for Cattles (10 %) 1.. 14 days) The cream is physically stable and shows no loss of iodine........................10 Vaseline .........................................10 Cetylstearyl alcohol........ 3. Stability (52 °C.................2 III..................10 Liquid paraffin ...... BASF Fine Chemicals Generic Drug Formulations 1998 ...............................6................................................... Mix the components II by heating....... Propylene glycol Pharma [1] .............................5 Water ....2 Cremophor A 25 [1] .... stir the solution I/III in the molten mixture II and cool by stirring.......... PVP-Iodine 30/06 (BASF) .................. Manufacturing Dissolve PVP-Iodine I in the solvents III.....

.......15...............1 Lutrol E 400 [1] ...................50... Administration Dilute 10 – 20 ml with a glass of water.....2 Anise oil + eucalyptus oil.....5.. Manufacturing Dissolve PVP-Iodine and saccharin in water and mix with solution II. Chemical stability (20–25 °C) 0 Months Available iodine Loss of iodine 0.89 % 2........82 % 2..7...................... BASF Fine Chemicals Generic Drug Formulations 1998 ............ Properties of the concentrate Brown transparent liquid having a fresh odour.....15..... 1+1 ............8 Liquid Formulations (Lab scale) Povidone-Iodine Mouth Wash and Gargle Solution Concentrate (7.........0 g g g g g g g 2........5 Saccharin sodium..0................5 %) 1..............................0 Ethanol 96 % ...91% – 6 Months 12 Months 0...... PVP-Iodine 30/06 (BASF) ........ 4....5 Water .0....2 % 0. II..2 % 5........ Formulation I.................. 3............... A brown liquid is obtained having a fresh taste.0 Menthol ............................0......

..9 ppm BASF Fine Chemicals Generic Drug Formulations 1998 ............ 0...................................................9 ppm 6.........................01 molar .....74 g Sodium hydroxide solution..........56 g 2........ Manufacturing Dissolve PVP-Iodine slowly in the solution of the salts.......1....................................0... Chemical stability (Stress test at 52 °C) Initial After 14 days pH.............0....... Properties of the solutions Clear..053 % 3.....0.1......6..................................055 % Loss of iodine ...................................... 3...8 mg Sodium chloride ...............40 g Potassium iodide .........– Free iodine . 4... brown liquid of low viscosity..97........8 Liquid Formulations (Lab scale) Povidone-Iodine Ophthalmic Solution (0.............0............7 0.....6 % 1....20 g Potassium iodate ......5......... Formulation PVP-Iodine 30/06 ..................4 %) 1..44...........2 Available iodine ...05 g Water ........................................

..39 g g g g 2........................0.............. Manufacturing Dissolve PVP-Iodine slowly in the solution of the salts............5...................0 %) 1........................16 % 0% 2............................................................... brown liquid of low viscosity........98.3 Available iodine ..................................................11 Water ..... Properties of the solutions Clear........ Formulation PVP-Iodine 30/06 .................. Chemical stability (Stress test at 52 °C) Initial After 14 days pH..........00 Potassium iodide ......1.....1.... 4.................0.........0.....6..9 ppm 7.....2 0............... 3..........................– Free iodine .....2 ppm BASF Fine Chemicals Generic Drug Formulations 1998 .............15 % Loss of iodine ..8 Liquid Formulations (Lab scale) Povidone-Iodine Ophthalmic Solution (1.......50 Potassium iodate .........

Formulation I...................0 Pentane ........ Manufacturing Suspend PVP-Iodine and Maize-PO4-Aerosol (I) in the liquid mixture II and fill in aerosol cans with the propellants III...50....... 1+3 ... Propane + butane.........25.............4 Formulation of granules. PVP-Iodine 30/06 M 10 (BASF)....25......1....... BASF Fine Chemicals Generic Drug Formulations 1998 ...4....10.5 Dow Corning 344 Fluid (DOW) ......0 Maize PO 4 Aerosol (Hauser) .... III...........0 II..0 g g g g g g 2.................................... Isopropyle myristate .......... dry syrups and Iyophylisates (Lab scale) Povidone-Iodine Powder Spray 1.....22..................

.00 Water ..........78..........0...........................75 Menthol..........00 Propylene glycol Pharma [1] ..........................................10...... At room temperature dilute with propylene glycol..... dissolve PVPIodine and add the flavours...1.......... .. Chemical stability After storage of 15 hours at 80 °C a loss on iodine of about 7 % has been determined........... Manufacturing Dissolve potassium iodide in water................10.... warm up to 40 °C and dissolve xylitol............. 3.....05 g g g g g g g 2......10 Xylitol ................... crystalline .10 Peppermint oil double rect... Properties of the solution Clear brown liquid with a sweet refreshing taste..0.......00 Potassium iodide ...............0..... BASF Fine Chemicals Generic Drug Formulations 1998 . 4.. Formulation PVP-Iodine 30/06 (BASF) ..5............8 Liquid Formulations (Lab scale) Povidone-Iodine Pump Spray (1%) 1.....

As soon as both are dissolved add slowly the PVP-Iodine to the well stirred solution...............0 g Natrosol® HR 250 (Hercules)........................... 2 PVP-Iodine 30/06 (BASF) ....... clear solutions having a certain viscosity and a pH of 3 – 4................... 1 No..............85........0 g Lutrol F 127 [1]...............– Citric acid solution 0.....2 g Sodium hydroxide...... add Texapon and slowly dissolve the PVP-Iodine.............5 g 28..– Sodium biphosphate solution 0.................8 Liquid Formulations (Lab scale) Povidone-Iodine Seamless Solutions (10 %) 1.......... 1 molar solution.. Manufacturing Formulation No........3.....5.... 1: Dissolve Lutrol F 127 and than Natrosol in the water............. 3...10......2 g 59..0 g – – – 2...2 molar.... 2: Dissolve Tylose M 300 in the mixture of the citric acid and sodium biphosphate solutions.......2 g Tylose ® M 300 (Hoechst) ........... Formulations No..........5........6 g 10....................... Properties of the solutions Brown......3 g – 2........ BASF Fine Chemicals Generic Drug Formulations 1998 .... Adjust the pH with the sodium hydroxide solution to about 3...– Water ....– Texapon ® K 12 (Henkel) .........1......0...1 molar......0 g 0.. Formulation No..........

.. After cooling incorporate Neutronyx...25....... BASF Fine Chemicals Generic Drug Formulations 1998 ...........0 Natrosol® 250 HR (Hercules) ......... 4. clear solution...... The viscosity can be changed by modification of the amount of Natrolsol 250 HR......5 Neutronyx® S 60 (Onyx) .......ad 100 g g g g g 2....0 Super Amide ® L 9 (Onyx) ... 52 °C) the loss of available iodine was about 12 %......7.. Formulation PVP-Iodine 30/06 (BASF) ..5........ 3.........0.....4... Chemical stability In the stress test (14 days............ Manufacturing Dissolve Super Amide and Natrosol in hot water (about 60 °C) and then dissolve PVP-Iodine.............7 Water ............8 Liquid Formulations (Lab scale) Povidone-Iodine Shampoo (7.........5 %) 1........... Properties of the shampoo Brown......5 – 0..

..................500 mPa · s BASF Fine Chemicals Generic Drug Formulations 1998 ...............7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Soft Gel (1%) 1........2..5 g Water.............. Formulation PVP-Iodine 30/06 (BASF) ...... Manufacturing Dissolve PVP-Iodine and Natrosol HR 250 in the well stirred water....... Properties of the gel Appearance........ 3..............0 g Natrosol® HR 250 (Hercules) ......................5 g 2....31..6. Viscosity (Brookfield.......1....Clear brown gel..96.... 23°C) ............

3.......... 1 year) 0 Month Available iodine pH BASF Fine Chemicals Generic Drug Formulations 1998 100 % 4....1 96 % 4...4 6 Months 12 Months 100 % 4........... 2 10... 1 (20–25 °C...– Citric acid 0.0 0... 4........3 0............– Lutrol E 400 [1] ........5...8 Liquid Formulations (Lab scale) Povidone-Iodine Solution (10 %).....0 g g g g g 2.46............... 1 PVP-Iodine 30/06 (BASF) .........10. Formulations No...5.4 g No..........2 46.. Manufacturing Dissolve the PVP-Iodine (and Lutrol F 127) in the mixture of the buffer solutions (and Lutrol E 400)..0 g Lutrol F 127 [1] ........ I 1....4 ..................... Chemical stability of formulation No.....2 molar solution.............43....5 43.. Properties of the solutions Brown clear solutions having a low viscosity and pH of about 4....6 g Na 2HPO 4 · 12H 2O 0......1 molar solution .........

5.8 Liquid Formulations (Lab scale)

Povidone-Iodine Solution
(10 %), II

1. Formulation
I. PVP-Iodine 30/06 (BASF) ......................10.00
II. Texapon ® K 12 (Henkel) ..........................0.03
III. Sodium biphosphate (Na 2HPO 4) ..............0.14
Sodium citrate........................................0.03
Sodium hydroxyde solution, 1 molar ........2.08
Glycerol .................................................1.00
Water ...................................................86.42

g
g
g
g
g
g
g

2. Manufacturing
Dissolve Texapon K 12 (II) in solution III and add slowly PVP-Iodine to the
well stirred solution.

3. Properties of the solution
Brown transparent liquid having a pH of 4.5.

4. Chemical stability
After production

After 14 days/52 °C

pH ...............................................4.5
Available iodine .......................1.08 %
Loss of iodine ..................................–

3.5
1.03 %
4.6 %

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Povidone-Iodine Surgical Scrubs
(7.5 %), I

1. Formulations
No. 1

No. 2

PVP-Iodine 30/06 (BASF) ...............................7.5 g
Neutronyx® S 60 (Onyx) ...............................25.0 g
Lutensit® AES (BASF) ..........................................–
Monoamide ® 150 MAW (Mono) ............................–
Super Amide ® L 9 (Onyx) ...............................4.0 g
Floral Bouquet ..............................................q. s.
Water .........................................................63.5 g

7.5 g

25.0 g
4.0 g

q. s.
63.5 g

2. Manufacturing
Dissolve Super Amide or Monoamide in hot water, cool, dissolve PVPIodine and add Neutronyx or Lutensit.

3. Properties of the scrub
Brown, clear viscous solution. The pH of formulation No. 1 is about 3.4

4. Chemical stability of formulation No. 1 (20–25 °C)
0 Month
Available iodine
pH

BASF Fine Chemicals Generic Drug Formulations 1998

100 %
3.6

6 Months 12 Months
99 %
4.3

87 %
4.6

5.8 Liquid Formulations (Lab scale)

Povidone-Iodine Surgical Scrubs
(7.5 %), II

1. Formulations
No. 1

No. 2

No. 3

PVP-Iodine 30/06 (BASF)............7.5 g
Texapon ® K 12 (Henkel) ............15.0 g
Lutensit® A-ES (BASF) .....................–
Fenopon ® CO 436 ...........................–
(Rhône-Poulenc)
Super Amide ® L 9 (Onyx)............4.0 g
Glycerol...........................................–
Water ......................................73.5 g

7.5 g

18.7 g

7.5 g


20.0 g

4.0 g

68.8 g

1.2 g
25.0 g
46.3 g

2. Manufacturing
Dissolve the surfactants in hot water (add glycerol) and incorporate the
PVP-Iodine.

3. Properties of the scrubs
Brown, clear viscous solution.

4. Stability (14 days at 52 °C)
No. 1

No. 2

No. 3

Loss of available iodine ............12.2 %

13.9 %

10.8 %

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Povidone-Iodine Teat-Dip Solution
for Cattles (3 %)

1. Formulation
PVP-Iodine 30/06 (BASF) ........................3.00
Glycerol .................................................8.00
Glacial acetic acid ..................................0.80
Sodium hydroxide solution, 50 % .............0.35
Water ..............................................ad 100.0

g
g
g
g
g

2. Manufacturing
Mix all liquid components and dissolve PVP-Iodine.

3. Properties of the solution
Brown transparent liquid having a pH of 4.3.

4. Chemical stability
After the storage at 52 °C during 14 days the loss of available iodine was
11.5 %.

BASF Fine Chemicals Generic Drug Formulations 1998

6.7 Formulations of semi-solid drugs (Lab scale)

Povidone-Iodine Transparent Ointment
(10 %)

1. Formulation
I.

II.

PVP-Iodine 30/06 (BASF) ........................10.0
Lutrol E 400 [1].......................................60.0
Sodium hydroxide, 1 molar solution ...........4.6
Water.......................................................0.4
Lutrol E 4000 [1].....................................25.0

g
g
g
g
g

2. Manufacturing
Prepare solution I, heat to about 60 °C, incorporate II stirring very well
and cool to room temperature.

3. Properties
Transparent ointment like a gel having a ph of 4. Miscible and washable
with water.

4. Stability (14 days, 52 °C)
The content of available iodine dropped only to 99 % and the pH to 3.6.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Povidone-Iodine Vaginal Douche
Concentrate (10 %)

1. Formulation
PVP-Iodine 30/06 (BASF) ........................10.0
Lutrol E 400 [1].........................................0.5
Lutrol F 127 [1] .........................................0.3
Citric acid, 0.1 molar solution ..................43.2
Na 2HPO 4 · 12H 2O, 0.2 molar solution ......46.0

g
g
g
g
g

2. Manufacturing
Dissolve PVP-Iodine and Lutrol F 127 in the mixture of the buffer
solutions with Lutrol E 400.

3. Properties of the solution
Brown, clear solution having a low viscosity and a pH of about 4.3.

BASF Fine Chemicals Generic Drug Formulations 1998

6.7 Formulations of semi-solid drugs (Lab scale)

Povidone-Iodine Vaginal Ovula
(5 %)

1. Formulation
PVP-Iodine 30/06 M 10 (BASF) ....................5 g
Lutrol E 400 [1]..........................................10 g
Lutrol E 4000 [1]........................................85 g

2. Manufacturing
Melt the Lutrol E grades by gentle heating. Stir in the micronized PVPIodine product in small portions into the melt.
After a uniform suspension has been obtained, pour it into polyethylene
moulds.

3. Properties
Homogeneous brown coloured ovula having a weight of 2.0 g.

4. Chemical stability
In a stress test (14 days/52 °C) and at room temperature (one year) no
loss of available Iodine were measured.

BASF Fine Chemicals Generic Drug Formulations 1998

6.7 Formulations of semi-solid drugs (Lab scale)

Povidone-Iodine Vaginal Ovula
(10 %)

1. Formulation
PVP-Iodine 30/06 M 10 (BASF)...................10
Lutrol E 400 [1] ...........................................5
Lutrol E 1500 [1] ........................................50
Lutrol E 4000 [1]........................................35

g
g
g
g

2. Manufacturing
Melt the Lutrol E grades by gentle heating. Stir in the micronized PVPIodine product in small portions into the melt.
After a uniform suspension has been obtained, pour it into polyethylene
moulds.

3. Properties
Homogeneous brown coloured ovula have a weight of 2.0 g.

4. Chemical stability
In a stress test (14 days/52 °C) and at room temperature (one year) no
loss of available Iodine were measured.

BASF Fine Chemicals Generic Drug Formulations 1998

5.8 Liquid Formulations (Lab scale)

Povidone-Iodine Viscous Solution
(1%)

1. Formulation
PVP-Iodine 30/06 (BASF) ..........................1.0 g
Natrosol® HR 250 (Hercules) .....................1.5 g
(Buffer.......................................................q.s.)
Water .....................................................97.5 g

2. Manufacturing
Dissolve PVP-Iodine and Natrosol in the well stirred water.

3. Properties of the solution
Clear brown viscous liquid.
Viscosity (Brookfield): 7,500 mPa · s

4. Chemical and physical stability
In a stress test (15 hours at 80 °C) the loss of iodine was 13.3 % and no
change of the appearance was observed.

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Prazosin Tablets
(5 mg)

1. Formulations
No. 1

No. 2

Prazosin hydrochloride, anhydrous (Knoll)..........5 g
Prazosin hydrochloride, polyhydrate (Knoll) ...........–
Ludipress [1] ..................................................94 g
Magnesium stearate [1] ....................................1 g


6g
93 g
1g

2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press with high
compression force.

3. Tablet properties
Weight ......................................................109 mg
Diameter ......................................................8 mm
Form ........................................................biplanar
Hardness ......................................................76 N
Disintegration ...............................................2 min
Friability .......................................................0.2 %

BASF Fine Chemicals Generic Drug Formulations 1998

103 mg
8 mm
biplanar
74 N
3 min
0.2 %

...155 Kollidon VA 64 [1] ..212 mg Diameter ........................................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ......................................5 Aerosil 200 [4] .10 Kollidon CL [1] .....< 1 min Friability........................8 mm Form .......................... pass through a 0.. Formulation Prednisolone ...................2 g g g g g g 2....20 Lactose monohydrate [8]..................................................................8 mm sieve and press with low compression force......................8 Magnesium stearate [2] .............9 Tablet formulations (Lab Scale) Prednisolone Tablets (20 mg) 1..............0........................................ 3............. Manufacturing (Direct compression) Mix all components.........2......................................biplanar Hardness................... Tablet properties Weight .................................................................................................63 N Disintegration .................................

.......8 mm Form .................... pass through a sieve and press with low compression force.........................................................................208 g Magnesium stearate [2] .................................... 3..........................................2 g 2......15 min...70 N Disintegration .2 % Dissolution..................0................ Formulation Prednisone...........................................2........................................82 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........................9 Tablet formulations (Lab Scale) Prednisone Tablets (10 mg) 1......4 min Friability...................................................................10 g Ludipress [1] ... Manufacturing (Direct compression) Mix all components........78 % 30 min ................ Tablet properties Weight .............................................biplanar Hardness.............223 mg Diameter ......

.................................3 g Magnesium stearate [2] ...........................................9 Tablet formulations (Lab Scale) Probenecid Tablets (500 mg) 1........................... Manufacturing (Wet granulation) Granulate mixture I with solution II...... add III and press with low compression force........130 g II.................................................... Probenecid .54 N Disintegration ..................................9 min Friability................ pass through a 0...........0.10 g Ethanol 96 % ............................................2....................................................8 mm sieve............12 mm Form . Kollidon CL [1] .............3 % Dissolution.................................................................. Tablet properties Weight ............. Formulation I.....biplanar Hardness....100 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................................................................. 5 min ..................................43 % 60 min.....3 g 2..............................674 mg Diameter ........... 3..............25 g Aerosil 200 [4] ............................. Kollidon 30 [1] ..70 ml III....500 g Corn starch [3] ...............

............q...... Manufacturing Suspend procain penicillin G in the well stirred solution II.......15 g Sodium citrate.........57 g Antioxidant............ Water of injectables ..................... 3......0....ad 100 ml 2....................0.8 Liquid Formulations (Lab scale) Procain Penicillin Injectable Suspension (300 mg/ml) 1.......................s..................................... BASF Fine Chemicals Generic Drug Formulations 1998 ..4 g Carboxymethyl cellulose.0....... Remark To prevent of discolouration of the dissolved Kollidon during storage 0..............................5 % of cysteine could be added as antioxidant..............q..........2 to 0........ Formulation I......... Preservative ....0 g Kollidon 17 PF [1] . II..................................homogeneous Redispersibility ......easy 4....................s... Properties of the suspension Aspect ........................5........... Procain Penicillin G .............30.....

.... Propanidide .ad 100 ml 2......0 g Cremophor EL [1] .........................................5.... Remarks – To reduce the viscosity and the side effects.20....... II.... Formulation I.......... Water for injectables ............. The sterilisation can be done by filtration or heat.... Properties of the solution A clear colourless solution was obtained. – During the heat sterilisation a separation of two layers can be observed.. s.0 g Preservatives..............q..8 Liquid Formulations (Lab scale) Propanidide Injectable Solution (50 mg/ml) 1....5......... 3... Manufacturing Mix propanidide with the warm Cremophor EL (60 °C) and add slowly the warm solution II... Cremophor EL could be substituted by Solutol HS 15 [1]................ BASF Fine Chemicals Generic Drug Formulations 1998 .. – In Germany Cremophor EL must be declared on the package of injectables. 4........ Shaking of the ampoules during cooling gives homogeneous clear solutions..........

............ 3 Weight ........ 1: 10 mg No....... 3.. 1 or No.................. 1 No..514 mg Diameter .... 3: 100 mg Propranolol hydrochloride ... Tablet properties No.2 % 505 mg 12 mm biplanar 101 N 3 min 0.12 mm Form .. Manufacturing (Direct compression) Mix all components.................. 2 No................ – These formulations can be used for tablet cores....... Formulation No............ 2: 50 mg No.............112 N Disintegration .................5 g 50 g 450 g 2....9 Tablet formulations (Lab Scale) Propranolol Hydrochloride Tablets (10 mg. BASF Fine Chemicals Generic Drug Formulations 1998 ...........1% 496 mg 12 mm biplanar 86 N 2 min 0...............0....1% 4...............2.2................5 g 2..10 g Ludipress [1] ........... pass through a 0..... Remarks – In the case of formulation No.....8 mm sieve and press with low compression force...490 g Magnesium stearate [2] ......5 g 100 g 400 g 2... too..........biplanar Hardness.. 2 the amount of Ludipress and the tablet weight could be reduced..........2 min Friability .......... 50 mg and 100 mg) 1........

.......................................................................108.......... Manufacturing (Direct compression) Mix all components.8 mm sieve and press with high compression force..........................3 min Friability......75 N Disintegration ............. pass through a 0..............................................................0 Magnesium stearate [2]..........0.........9 Tablet formulations (Lab Scale) Propranolol Tablets Cores (40 mg) 1..........3 Stearic acid [7] ... Tablet properties Weight ...................40...150 mg Diameter .8 mm Form ................ 3.................................................0................................4 g g g g 2.............. Formulation Propranolol ............biconvex Hardness.................2..........................0............2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...0 Ludipress [1] .................................

................1 mg BASF Fine Chemicals Generic Drug Formulations 1998 ............. s.38 °C Inlet flap .................................15 min.......5 Coating formulations (Lab Scale) Protective Film Coating with Ethyl Cellulose + Kollidon VA 64 1.......3 bar Spraying time........................ Coating procedure (Fludized bed) Tablet core loading ......59 g Isopropanol ................. Formulation I..........40 °C Outlet air temperature ... Pass this mixture through a colloid mill and add solution II..Position 10 Outlet flap......................... Quantity of film forming agent/cm 2 ........................................................ Final drying..20 g Talc............................... add the water and suspend the colorants and the talc................Positon 4 Spraying pressure .............5 kg Inlet air temperature .......3...........................q................................................................................................................................13 g Sicovit Colour lake [1] ........... Kollidon VA 64 [1] ..................................................................98 g Water..................................................................140 g Water..... 3.......................... Manufacturing of the suspension Dissolve Ethocel and Kollidon VA 64 in isopropanol.............2 min......... II.......................5 g Ethocel ® 20 (Dow) ............................5 g Sicovit Titanium dioxide [1] ........ Isopropanol..60 g 2..........................

.................................8 mm 25 g 3.........3....................................... Manufacturing of the suspension Dissolve Klucel and Kollidon VA 64 in isopropanol or water and suspend the colorants and the talc.................8 mm Quantity of sprayed suspension/min......2 s Nozzle (Walther WA XV) ..740 g 20 g 20 g – q..........6 s Interval ........2 kg Amount of coating suspension ...............0............................... Isopropanol ...................... 1 No............ 760 g – 2...5 s 6s 2s 0................................ s................. 2 Tablet core loading ........3 s Interval.....................................6.8 g Quantity of solids applied on each tablet core...........................................– Water ..................................5 – 6 h 2 kg 800 g 6s 0..............0....3....... 1 No......... Pass this mixture through a colloid mill................ 2 Kollidon VA 64 [1] ..20 g Sicovit Colour lake or Pigment [1]..................5 s Drying phase (warm air) ............5 Coating formulations (Lab Scale) Protective Film Coating with Hydroxypropyl Cellulose + Kollidon VA 64 1............................................ Formulations No........... s........1 mg Total coating time ............. 3.........................................20 g Talc ......800 g Spray phase........... Coating procedure (Sugar coating pan) No..............q..................................................................................20 g Klucel ® EF (Hercules) ......2 mg 1h BASF Fine Chemicals Generic Drug Formulations 1998 ......

........................60 °C Outlet air temperature ....40 °C Nozzle.18 Talc [10] ....5 min at 60 °C Quantity of film former applied ............ 3.................12 rpm Spraying pressure ........5.............. II.........5 Coating formulations (Lab Scale) Protective Film Coating with Hydroxypropylmethyl Cellulose + Kollidon VA 64 1.................3.......54 Water .......................................9 mm biconvex Amount of coating suspension applied........ Coating procedure (Accela Cota 2499) Tablet core loading ........1.0 bar Spraying rate ....34 min Final drying...................................................0 mm Rotation speed of the pan ....0 kg Core size .... Suspend the pigments and talc in 216 ml of water and pass this mixture through a colloid mill................................. Pharmacoat ® 606..50 g/min Spraying time (continuously) ........ Manufacturing of the suspension Dissolve Lutrol E6000 and Kollidon VA 64 in 732 ml of water.....................................79 (e....................... Formulation I..................... Kollidon VA 64 [1] .........2 kg Inlet air temperature .14 mg/cm 2 BASF Fine Chemicals Generic Drug Formulations 1998 .36 Sicovit Iron oxide Red 30 [1].......... add HPMC and stirr 45 min avoiding the formation of too much of air bubbles. To obtain the final coating suspension mix solution I with suspension II............12 HPMC 6 mPa · s ......................................................732 Sicovit Titanium dioxide [1] ................................................................................... Shin-etsu) Water...........................................216 1200 g g g g g g g g g 2...................................1.............. g..............................2 min Drying after spraying.................3...............2........................53 Lutrol E6000 [1] ....

..............................................5 Sicovit Iron oxide or Lake [1] ..........50 Water ............000 g g g g g g g 2..............Walther WAXV with 1-mm nozzle Spraying time ................................15 Sicovit Titanium dioxide [1] ...........5 Coating formulations (Lab Scale) Protective Film Coating with Kollidon VA 64 1....... Manufacturing A 500-g sample of this suspension was passed through a disk mill and sprayed under the following conditions: Sugar-coating pan Spray gun .Walther WAXV with 0..............................0...........................2 bar Spraying time ...............................................................................6 sec Pause............................30 Talc [10] ............................5 sec Dry air ...............ad 1.........3 sec Accela Cota 2499 (continuous spraying) Spray gun ..38 °C Spraying pressure ..........................50 Lutrol E 6000 [1]........3...............8-mm nozzle Temperature at inlet ......45 °C Temperature at outlet............................................40 Glycerol ...........................................$ 50 min BASF Fine Chemicals Generic Drug Formulations 1998 ............................. Formulation Kollidon VA 64 [1] ...................................................................3 sec Pause...................................................................................................

BASF Fine Chemicals Generic Drug Formulations 1998 . Remark If the film is to sticky a certain part of Kollidon VA 64 should be substituted by HPMC or sucrose.3.

.... 3............88...............5.................................................................................... Suspend the pigments and talc in 168 ml of water and pass this mixture through a colloid mill....................1........about 3 mg/cm 2 BASF Fine Chemicals Generic Drug Formulations 1998 ...................... To obtain the final coating suspension mix solution I with suspension II...................59 °C Outlet air temperature ..............18 g Talc .....0 mm Rotation speed of the pan ............................................840 g Sicovit Titanium dioxide [1] .......46 °C Nozzle... Kollidon VA 64 [1] .... Manufacturing of the suspension Dissolve Lutrol E6000 and Kollidon VA 64 in 840 ml of water.......15 rpm Spraying pressure .........................................................56 g Water .... II................................ Formulation I.............83 min Final drying............................1...5 min Quantity of film former applied ..... add the polyvinyl alcohol and stirr 45 min avoiding the formation of too much of air bubbles..... Hoechst)................50 g Lutrol E6000 [1] ..0 kg Amount of coating suspension.........37 g Sicovit Iron oxide red [1]..0 bar Spraying rate .....................................5 Coating formulations (Lab Scale) Protective Film Coating with Polyvinyl Alcohol + Kollidon VA 64 1.....168 g 1257 g 2............................76 g Water............ Coating procedure (Accela Cota 2499) Tablet core loading ...........2.............................12 g Polyvinyl alcohol (Mowiol ® 8........3.................................26 kg Inlet air temperature ...15 g/min Spraying time (continuously) ............................

.. Formulation Shellac .....65 Cetyl alcohol ..185 Talc ...............................30 Sicovit Colour lake [1] ........ Add titanium dioxide..3..................................................................20 Sicovit Titanium dioxide [1]...........................50 Isopropanol or ethanol ....458 g g g g g g g g 2...................5 Coating formulations (Lab Scale) Protective Film Coating with Shellac + Kollidon 30 1....................................... Application of the coating suspension About 50 g suspension were applied to 1 kg of tablet cores in a conventional coating pan or in a Accela Cota pan (1 – 2 mg film formers/cm 2) BASF Fine Chemicals Generic Drug Formulations 1998 .................................15 Sorbitane trioleate ................... talc and the lake and mix in the colloid mill. 3...........................177 Kollidon 25 or 30 [1] ............. Manufacturing of the coating suspension Dissolve shellac and sorbitane oleate in the warm solvent and then Kollidon and cetyl alcohol....................

...biplanar Hardness....................q.......192 mg Diameter ................................8 mm Form .........95 g III........... (+) Pseudoephedrine hydrochloride (Knoll) ......................2 g 2.............. Polyethylene glycol 6000.........82 N Disintegration ...................................60 g II..............2....... IV............................ mix with I.. pass through a 0.... Tablet properties Weight ............. DI-TAB [9] ......... Kollidon 30 [1] ............................. Dicalcium phosphate.............................4 min Friability.......................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................... dry........... Manufacturing Granulate dicalcium phosphate II with solution III..................... Formulations I..... 3...........9 Tablet formulations (Lab Scale) Pseudoephedrine Tablets (60 mg) 1.....s...................8 mm sieve..20 g Aerosil 200 [4] .............. powder [6].................... add IV and press with low compression force..0.......................5 g Water...........

...........9 Tablet formulations (Lab Scale) Pyrazinamide Tablets (500 mg)......12...................biplanar Hardness.............................12 mm Form .5 Kollidon CL [1] ............89 % BASF Fine Chemicals Generic Drug Formulations 1998 ..................................0 Aerosil 200 [4] .....45 seconds Friability........................................36 % Dissolution......... 3...........................................96 N Disintegration ..........................................................8 mm screen and press with medium compression force........... sieve through a 0...... Tablet properties Weight ............................2................................ DC 1...3...............0.....134...............................500.....652 mg Diameter .................. Manufacturing (Direct compression) Mix all components.................. Formulation Pyrazinamide.....................0 Ludipress [1] ..................5 g g g g 2..... 45 min .......

20 g Ethanol 96 % .......................... 200 ml III.......................................6 g 2..............96 % BASF Fine Chemicals Generic Drug Formulations 1998 ................................8 mm sieve..................................................................... WG 1..25 % Dissolution.....biplanar Hardness .....(5-) 10 g Magnesium stearate [2] ..................... 3...................12 mm Form .......78 % 30 min .....0..............131 N Disintegration .. Formulation I........................................... 15 min............. Pyrazinamide.........approx............................................. pass through a 0... Tablet properties Weight .............................. mix with III and press with low compression force..50 g II.............3 min Friability.................................500 g Corn starch [3] .........9 Tablet formulations (Lab Scale) Pyrazinamide Tablet (500 mg)........................................... Kollidon 30 [1] ............................. Manufacturing (Wet granulation) Granulate mixture I with solution II................ Kollidon CL [1] ...605 mg Diameter .......2.......................................

......... Formulation Ranitidine .......................0................................................305 mg Diameter ...................................8 mm screen and press with low compression force....... 3........................61 N Disintegration .........biconvex Hardness........8 mm Form ............... Tablet properties Weight ........................................147 mg Magnesium stearate [2].......3 mg 2.................................................... Remark If the flowability of the tabletting mixture is not sufficient about 1% Aerosil 200 [4] could be added...... Manufacturing (Direct compression) Mix all components............. pass through a 0........150 mg Ludipress [1].......................................................................5 % 4..2......... BASF Fine Chemicals Generic Drug Formulations 1998 ...........2 – 3 min Friability...9 Tablet formulations (Lab Scale) Ranitidine Tablet Cores (150 mg) 1............

..............600 mg Diameter ..................295 Magnesium stearate [2] .................300 Ludipress [1] ...........2....72 N Disintegration ............... Formulation Ranitidine..9 Tablet formulations (Lab Scale) Ranitidine Tablet Cores (300 mg) 1... Tablet properties Weight ............................5 g g g g 2..................... 45 min .....................95 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................0................................................................................................. Manufacturing (Direct compression) Mix all components..............8 mm screen and press with low compression force..5 Aerosil 200 [4] ...............................................5 min Friability ............................ pass through a 0........biconvex Hardness................................................................12 mm Form .......................6 % Dissolution.. 3.......................................

...........biplanar Hardness.........1 – 2 min Friability ..................................................12 mm Form ...9 g Isopropanol or ethanol 96 % ...................... Manufacturing (Wet granulation) Granulate mixture I with solution II.......6 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........................................................550 mg Diameter ...............2 g Aerosil 200 [4] .......................................................9 Tablet formulations (Lab Scale) Rifampicin Tablets (450 mg) 1.......15 g Stearic acid [7] .....................................50 ml III............................................ Kollidon CL [1]...................................95 N Disintegration ....................2.....58 g II.................................................... Tablets properties Weight ..... sieve and mix with the components of III and press with low compression force to tablets..................10 g Magnesium stearate [2] . dry.......................... 3........ Formulation I.................................................................. Rifampicin ..... Kollidon 90 F [1] ....2 g 2........450 g Corn starch [3] ................0.....................

............0................ Formulation Saccharin sodium ... pass through a 0......................2............................ powder [6]......................10 g Sodium bicarbonate ....................5 mm Form ...............14 g Kollidon VA 64 [1] .........................9 Tablet formulations (Lab Scale) Saccharin Effervescent Tablets (15 mg) 1......1 min Friability ... water) ............................................................... 3..........2 g Polyethylene glycol 6000.........................................................................................15 g Tartaric acid ..biplanar Hardness..8 mm sieve and press with low compression force....................... Manufacturing (Direct compression) Dry saccharin sodium and tartaric acid 1 hour at 100°C..............................42 mg Diameter .. Mix all components.2 g 2........................................23 N Disintegration (45 °C.......... Tablet properties Weight .........6 % BASF Fine Chemicals Generic Drug Formulations 1998 .

.. pass through a 0.................biplanar Hardness ....2..0........... powder [6] ...< 2 min Friability ..........3 g Polyethylene glycol 6000....0 g Kollidon CL [1] .2 % BASF Fine Chemicals Generic Drug Formulations 1998 51 mg 5 mm biplanar 29 N < 2 min 0...0 g Lutrol F 68 [1].............................. Formulations No.31...........................................................................................0 2.......0 g Ludipress [1] .15.8 mm sieve and press with medium compression force................. 1 Saccharin sodium (Roth) ....... 2 15........................0............................................................9 Tablet formulations (Lab Scale) Saccharin Tablets (15 mg) 1....................................2...3 g g g g – 2..........................0 g Magnesium stearate [2] .................5 mm Form ...........0 0...... milled < 100 µm ...... 3...51 mg Diameter ...................................... Tablet properties Weight ............. Manufacturing (Direct compression) Mix all components..............33 N Disintegration (water) ........– No...0 g 2..........................0 31...2 % ............2........

..................................................................................... Manufacturing (Direct compression) Mix all components intensively...81 N Disintegration .................... pass through a 0.....................1% BASF Fine Chemicals Generic Drug Formulations 1998 ..........3 – 4 min Friability ...............9 Tablet formulations (Lab Scale) Selegiline Tablets (5 mg) 1.............. Formulation Selegiline (Knoll) .............................1 g 2........................< 0....biplanar Hardness...............8 mm sieve and press with low compression force.....................................................................5 g Ludipress [1] .... Tablet properties Weight .6 mm Form ...........2.................... 3..............................................94 g Magnesium stearate [2] ..................99 mg Diameter ....

..............< 0.....................238 mg Diameter ..............................2 g 2...........................................................................................................2 % BASF Fine Chemicals Generic Drug Formulations 1998 .........................................3 – 4 min Friability ........80 N Disintegration ..............8 mm sieve..... 3............................................2......biplanar Hardness...... Manufacturing (Direct compression) Pass all components through a 0.................................9 Tablet formulations (Lab Scale) Serratio Peptidase Tablets (10 mg) 1.....228 g Magnesium stearate [2] ............................8 mm Form . mix intensively and press with low compactation force (6 kN)........ Formulation Serratio peptidase ...... Tablet properties Weight ...........10 g Ludipress [1] ................

..< 0.........5 g Ludipress [1] ..........................biplanar Hardnes.....4.....................................................2....35..........12 mm Form ...........................1% Disintegration ............................................8 mm sieve and press with low compression force (about 10 kN).....................410.....................5 g 2.......0......................1% BASF Fine Chemicals Generic Drug Formulations 1998 ..3 min Friability ... Tablet properties Weight ..458 mg Diameter ......... pass through a 0.. 3......................................................5 g Magnesium stearate [2]..... Manufacturing (Direct compression) Mix all components........9 Tablet formulations (Lab Scale) Silimarin Tablets (35 mg) 1................ Formulation Silimarin ...................................................................

...........biplanar Hardness........q............... mix throroughly......0 g Sucrose..280....> 30 min Friability .................. Tablet properties Weight .. and press with high compression force................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...........158........ III.............8 g 2.. dry.....................................s............0 g Kollidon 90 F [1] ...... Aerosil 200 [4] ...................................2................... add mixture III.9 Tablet formulations (Lab Scale) Simethicone Chewable Tablets (70 mg) 1.........5 g Isopropanol ....8 g Magnesium stearate [2]............ Formulation I.............................12 mm Form ...............................2...........3............40 N Disintegration ......................................7....... pass through a 0... 3............................ Manufacturing (Wet granulation) Granulate mixture I with solution II.......... Kollidon 90 F [1] .........................................442 mg Diameter ..< 0....8 mm sieve.......0 g II.. powder .........................................2. Simethicone dry powder 25 % ....................

......................................................................... Simethicone (Wacker Siliconoil S 184) .9 Tablet formulations (Lab Scale) Simethicone Chewable Tablets (80 mg) 1...............................................................................8 mm sieve................. Ludipress [1] ...............................2..8 g g g g g g 2.............< 0...............2 Magnesium stearate [2] ......81 N Friability ..400 Aerosil 200 [4] .......20 III......870 mg Diameter ......... mix thoroughly.................................................... add mixture III....... Tablet properties Weight .................. crystalline [10] ..biplanar Hardness.........80 Sorbitol.... powder ....... 3.....................16 mm Form ..8 mm sieve and press with high compression force............ Formulation I............................ II. Manufacturing (Granulation) Mix the components II with the simethicone oil I. pass again through a 0... pass through a 0..................390 Menthol..........1% BASF Fine Chemicals Generic Drug Formulations 1998 .

................................. dry syrups and Iyophylisates (Lab scale) Simethicone Instant Granules (60 mg and 120 mg) 1....0 g Ethanol .............4...... 2................ – Easily dispersible in cold water without any physical separation during 30 min.... dry and pass through a 1 mm sieve.........0 g Fructose (Merck) . crystalline (Merck) . Administration Take the content of one sachet (1 g = 60 mg simethicone or 2 g = 120 mg simethicone) as powder or disperse the recommended amount (e.....0 g Kollidon CL-M [1]... Sorbitol.. 3. Manufacturing Introduce solution II into the mixture I.10.......................50.. Kollidon VA 64 [1] .. BASF Fine Chemicals Generic Drug Formulations 1998 ...5 g I................ 4....0 g III.0 g II....g................. – 98 % coarser than 50 µm.....4 Formulation of granules..........40. Fill 1 or 2 g in sachets.............50......0... Goldschmidt) ............. Formulation Simethicone (Abil ® 200..... 1 to 2 g) in 100 ml of drinking water.............. Granulate the powder mixture III with the well stirred mixture I/II....0 g Orange flavour (Dragoco) ...5...... Properties of the granules – Free flowing white granules.3......0 g Cremophor RH 40 [1] .......50....

.........1..................5....... Remark Preservatives could be added if it is needed..........1 to 0. BASF Fine Chemicals Generic Drug Formulations 1998 ...0 ml 2....100....very low 4.5 % of cysteine could be added as antioxidant................ Properties Appearance ..........clear Viscosity..........8 Liquid Formulations (Lab scale) Sobrerol Injectable Solution (75 mg/5 ml) 1................2 µm filter.......... Manufacturing Dissolve sobrerol slowly in the well stirred solution of Kollidon 17 PF......... Formulation Sobrerol.................... 3..................... The sterilisation can be done by filtration through a 0...........5 g Kollidon 17 PF [1] .....6......... To prevent of discolouration of Kollidon in the solution during storage 0..............0 g Water for injectables................

.......25 Kollidon VA 64 [1] ..................... Manufacturing (Direct compression) Mix all components...56.......................biplanar Hardness ...... DI-TAB [9] .............116 mg Diameter ...................8 – 9 min Friability ....... Remark If the content uniformity is not sufficient a premix of sodium fluoride and sorbitol or DI-TAB should be prepared separately before mixing with the rest of the excipients.144 N Disintegration .8 mm sieve and press with high compression force...55 Sorbitol......................................................25 Dicalcium phosphate..............< 0........1% 4......................... Formulation Sodium fluoride (Merck) ..........0..........5 mg) 1............................................2.............................20 Magnesium stearate [2].............. BASF Fine Chemicals Generic Drug Formulations 1998 ..........2..56.............0...... 3.....6 mm Form ........50 g g g g g 2........................ crystalline [10] ..9 Tablet formulations (Lab Scale) Sodium Fluoride Tablets (0........ Tablet properties Weight............... pass through a 0.....................

. Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation.........2... Tablet properties Weight ............................................82 N Disintegration ............3 g Ludipress [1] ................................. BASF Fine Chemicals Generic Drug Formulations 1998 ..........78 mg Diameter .................................................................8 mm sieve and press with low compression force............biplanar Hardness.......< 0.. pass through a 0............4 g 2.........................3 mg) 1........0....................4 min Friability ....1% 4......... 3.........1.......5 mm Form ........................................76...................................... Formulation Sodium fluoride (Merck) ......9 Tablet formulations (Lab Scale) Sodium Fluoride Tablets (1....................... Manufacturing (Direct compression) Mix all components.7 g Magnesium stearate [2].....

... 3....153 N Disintegration....................................5 g 2...........25..........................................................0 g Magnesium stearate [2]............................ Manufacturing (Direct compression) Mix all components.......175.............................1% BASF Fine Chemicals Generic Drug Formulations 1998 .......... pass through a sieve and press with medium compression force..2...........................................................13 min Friability .............8 mm Form ..................................................1.......0 g Ludipress [1].............< 0.......9 Tablet formulations (Lab Scale) Spironolactone Tablets (25 mg) 1...197 mg Diameter ................biplanar Hardness ................................. Formulation Spironolactone .. Tablet properties Weight ...............

..................................................................245 g Polyethylene glycol 6000... 3..................25 g Aerosil 200 [4] ...........149 N Disintegration (water).........not tested Friability....................................................................................495 mg Diameter ... Manufacturing (Direct compression) Mix all components.....................biplanar Hardness ...................5 g 2....................................... Tablet properties Weight ............. powder [6]................. Formulation Spirulina extract..............12 mm Form ......... pass through a 0...........2.......2 % BASF Fine Chemicals Generic Drug Formulations 1998 .0....................9 Tablet formulations (Lab Scale) Spirulina Extract Chewable Tablets (250 mg) 1.......... powder ......250 g Ludipress [1] ..................8 mm sieve and press with medium compression force.....

..3..... Remark No plastisizer is needed in this formulation due to the plasticity of Kollidon VA 64. Formulation Kollidon VA 64 [1] . Manufacturing (Accela Cota) Spray the solution onto the warm tablet cores (30 – 40 °C) for few minutes before to continue with the aqueous main coating procedure..........4 mg/cm 2 tablet surface is sufficient for a good subcoating protection.........900 g 2.............. 3.100 g Ethanol or isopropanol ..... BASF Fine Chemicals Generic Drug Formulations 1998 ................. The amount of 0..5 Coating formulations (Lab Scale) Subcoating for Core Protection 1.......

.. Formulation I............................................................................................660 mg Diameter ............ 3...........................90 N Disintegration ......9 Tablet formulations (Lab Scale) Sucralfate + Sodium Alginate Tablets (500 mg + 20 mg) 1....... Manufacturing (Wet granulation) Granulate mixture I with solution II.................0.............2.. Sucralfate ................20 g Ethanol 95 % .............................12 mm Form .........................3 – 4 min Friability............................................80 ml III....500 g Sodium alginate ....20 g Corn starch [3] ............................ Kollidon CL [1] .70 g II..................................................... Tablet properties Weight ..30 g Magnesium stearate [2] .. mix the dry granules with III and press with low compression force....................3 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................biplanar Hardness................. Kollidon 30 [1] ......................3 g 2.... pass through a sieve...........................................................................................................

............... Ind....10 min....40 g Water............ Glycerol ............................................... than mix with glycerol..............5 Coating formulations (Lab Scale) Sugar Coating............................................. Total coating time .......q.......... s..............................5 s Interval ........16 h BASF Fine Chemicals Generic Drug Formulations 1998 . Coating procedure 4 kg of tablet cores with a weight of 420 mg were sprayed with 2....5 kg of the above suspension in a conventional coating pan under the following conditions: Spray phase ....................90 g Calcium carbonate ............................................ Drying phase (warm air) ......630 g 2............760 g Kollidon 30 [1] ........ Formulation of the coating suspension Sucrose ..........................5 (1996) 221 – 304) 1.....3..................................... Pharm.....................290 g Sicovit Colour lake [1] ............10 min................. 3............ 28.. automatic (According to Nürnberg..............................................90 g Talc ...................... Manufacturing of the coating suspension Dissolve the sucrose in the hot water................ dissolve Kollidon 30 and suspend the other components..............80 g Sicovit Titanium dioxide [1] ....

.6 10. 2 Coloured 16.0 5.... Manufacturing of the coating suspensions Dissolve Kollidon.. BASF Fine Chemicals Generic Drug Formulations 1998 ....3..........8 g Carmelose sodium............5 Coating formulations (Lab Scale) Sugar Coating....14...3 115.1..........135 g Water......7 g Talc ................................................... Remark The polishing can be done by means of a solution of beeswax or polyethylene glycol 6000. 4... After changing to formulation No.5.0 g Polysorbate or Cremophor RH 40 [1] ..... Polysorbate or Cremophor and sucrose in the water and suspend the other components in this solution.......3 g Sicovit Titanium dioxide [1] ....135 1...0 17.............................. 1 by means of the manual sugar coating procedure during some hours...6 g Aerosil 200 [4] ...........10.........650 g g g g g g g g g 2.............3 3.............650 g No................– Sucrose .............. 1 White Kollidon 30 [1] ... Application of the coating suspension Start with formulation No... 3.............. 2 continue with the same procedure until homogeneous coloured sugar coated tablets are obtained............................ Formulations No...81.16............. Mix in a colloid mill...............70 g Sicovit Colour lake or Pigment [1].....3....................................8 14...7 81........ manual 1......................

....................0...2 kg Inlet air temperature ............................ Kollidon VA 64 and Lutrol E 4000 in the water and suspend the other components......................................... Manufacturing of the coating suspension Dissolve the sucrose.........................0 bar Spraying time (continuously) ..................50 Sicovit Titanium dioxide [1] .......1................. Coating procedure (Accela Cota 2499) Tablet core loading ...........50 Water ..................................40 Talc ...15 Lutrol E 4000 [1]...................45 °C Outlet air temperature ................................. Pass through a colloid mill.....................................4 mg/cm 2 BASF Fine Chemicals Generic Drug Formulations 1998 ........200 Kollidon VA 64 [1] ..............................................................................8 mm Rotation speed of the pan ...............2.............ad 1200 g g g g g g g 2.............5 Coating formulations (Lab Scale) Sugar Film Coating 1...15 rpm Spraying pressure .............30 Sicovit Colour lake [1] ............... 3...............0 kg Amount of coating suspension .............. Formulation of the coating suspension Sucrose .................3....50 min Quantity of film former applied .........35 °C Nozzle.......5...........................

5....8 Liquid Formulations (Lab scale) Sulfadiazine + Trimethoprim Veterinary Concentrated Oral Suspension (40 % + 8 %) 1..8 Sodium hydroxide ..........................40 Trimethoprim.................. Manufacturing Dissolve sodium hydroxide in water and suspend the active ingredients and Kollidon CL-M......... Formulation Sulphadiazine......................... It showed some sedimentation after 7 days but the redispersibility was very easy..........................................................44 g g g g g 2.....6 Kollidon CL-M [1] ......................... The pH was 12......2 Water.................... 3.......................... BASF Fine Chemicals Generic Drug Formulations 1998 ....... Properties of the suspension A homogeneous white suspension was obtained....

............................0... Kollidon CL [1]......0 g II.........8 g Aerosil 200 [4] ..... 3.....................3 min Friability .............................12 mm Form ........ Tablet properties Weight .............0 g III.......9 Tablet formulations (Lab Scale) Sulfadiazine Tablets (450 mg) 1........... Formulation I.......602 mg Diameter ..................... Manufacturing (Wet granulation) Granulate mixture I with solution II.................................1% Dissolution...........................4 g Talc [10] ...........2 g 2...2.......................... Sulfadiazin ............200.....................................................................................14............... Kollidon 30 [1] ............8 mm sieve..93........87 % 30 min ...... dry........................................................................1..........................................................0 g Water .77 % 20 min .......biplanar Hardness ...............23................ pass through a 0.................0...............0 g Lactose monohydrate D 20 [8] .................... 10 min...152 N Disintegration ...............2 g Calcium arachinate [2] ........< 0....................................... add mixture III and press with low compression force.465............................89 % BASF Fine Chemicals Generic Drug Formulations 1998 ....

............ BASF Fine Chemicals Generic Drug Formulations 1998 ....................2 to 0... 3........................................................clear pH....5..................... Manufacturing Mix solution I slowly with solution II at 60 °C and cool..............40 ml Propylene glycol Pharma [1] .... Properties of the solution Appearance .. Water for injectables ....7 Viscosity......very low 4.8 Liquid Formulations (Lab scale) Sulfadimethoxine Veterinary Injectable Solution (2.....5 % of cysteine could be added as antioxidant............q............q..................... 5...................... Sulfadimethoxine.............. II.............5 % = 250 mg/10 ml) 1.........................70 g Antioxidant... Remark To prevent of discolouration of Kollidon in the solution during storage 0......... s............................... s. Formulation I.................... Physical stability (20–25 °C) No recrystallisation after some weeks.5 g Ethanol 96 % ....................... ad 200 ml 2.....................40 ml Kollidon 12 PF [1] .....

.................500...........0 II........................... dry.... pass through a 0................8 mm sieve..........................2........... mix with III and press......610 mg Diameter ...........9 Tablet formulations (Lab Scale) Sulfadimidine Tablets (500 mg) 1.................................0 III............200......120 N Disintegration.. Kollidon CL [1]............................................................................................0..........100.............0............... Kollidon 30 [1] ............. Manufacturing (Wet granulation) Granulate mixture I with solution II........................................... 3.0 Water .........................15...................0....7 % BASF Fine Chemicals Generic Drug Formulations 1998 ...0 Talc [10] ...... Tablet properties Weight ..................2 – 3 min Friability.............................4 Aerosil 200 [4] ... Formulation I.......25...................3 Calcium arachinate [2] ............................3 g g g g g g g g 2.0 Lactose monohydrate [8]........biplanar Hardness .........12 mm Form .....2........................................... Sulfadimidine (Cilag) ................

.........5 BASF Fine Chemicals Generic Drug Formulations 1998 ....... s................8 Liquid Formulations (Lab scale) Sulfadoxine + Trimethoprim Veterinary Injectable Solution (1000 mg + 200 mg/10 ml) 1.0 g Water for injectables ..... colourless pH...... 2...............5......................... and set to pH 8...29.....5 with sodium hydroxide.2................0 g Trimethoprim ..........clear...........................................56........0 g Sodium hydroxide .....0 g Soluphor P [1] ........... Manufacturing Disolve sulfadoxine and trimethoprim in Soluphor P.................... 3............... add the water..8.................. Formulation Sulfadoxine ....................................q...........10........... Properties of the solution Appearance ......

...0 g Lutrol E 400 [1]........2.... 4..... 3................30.. BASF Fine Chemicals Generic Drug Formulations 1998 ..........................0 g 2............68.0 g Preservative ..5............q............................... s......... Formulation I.. Water........... Physical stability No change of the clarity after 2 weeks stored at 6 °C and at 20 – 25 °C........ Sulfadoxine ................... colourless solution of low viscosity was obtained....8 Liquid Formulations (Lab scale) Sulfadoxine Solution (2 % = 20 mg/ml) 1. Properties of the solution A clear.. Heat the solution II to the same temperature and mix slowly with solution I....... II. Manufacturing Prepare solution I at 60 °C................

.....................2 g Magnesium stearate [2] ......115 N Disintegration ............. 3..............................................................................................2.............. add III and press with low compression force............................... dry...............6 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........0.......... Sulfamethoxazole ...............8 g 2..............546 mg Diameter ................................ Formulation I........................q.... Manufacturing (Wet granulation) Granulate mixture I with solution II.........400 g Trimethoprim .80 g II............. Kollidon CL [1] ........................... Tablet properties Weight .............9 Tablet formulations (Lab Scale) Sulfamethoxazole + Trimethoprim Tablets (400 mg + 80 mg) 1.............. III..........8 mm sieve...........................................s...9 min Friability ...................................biplanar Hardness ................ pass through a 0................................................................. Kollidon 30 [1] ..............15 g Isopropanol .......12 mm Form ........................24 g Talc [10] ....

......10............................................0......1 Chocolate flavour ................1 Sodium benzoate .......... 3........ crystalline [10] ................8 Sorbitol..0 Sodium gluconate ......... Manufacturing Mix all components and sieve for administration...0.............. 4................1 Saccharin sodium ................ Preparation of the administration form Shake 55 g of the powder with 100 ml of water until a homogeneous suspension is obtained...... Properties of the obtained suspension No sedimentation during more than 24 hours..4....4 Formulation of granules.............0 Kollidon CL-M [1]...0 Sodium citrate.............0 Trimethoprim .....5.................. Formulation Sulfamethoxazol .....................30....0..... dry syrups and Iyophylisates (Lab scale) Sulfamethoxazol + Trimethoprim Dry Syrup (400 mg + 80 g/10 ml) 1.0.....................................................0.....................................1 g g g g g g g g g g 2...............0 Vanillin ..5........... Fill 55 g of the mixture in a 100 ml flask...4........... BASF Fine Chemicals Generic Drug Formulations 1998 ............ The redispersibility is very easy after 2 weeks......

....... Formulations No............... 2 Sulfamethoxazole ................ Manufacturing Sieve the components I.........0 g Trimethoprim....10................. Vanillin ........0 g II........very easy beige very low very few easy BASF Fine Chemicals Generic Drug Formulations 1998 ...8 Liquid Formulations (Lab scale) Sulfamethoxazole + Trimethoprim Oral Suspension (400 mg + 80 mg/5 ml) 1...............beige Viscosity: ............0.....2 g 8...............s.......... q............. suspend in solution II and add the flavours III...6 g Kollidon CL-M [1] .............0................... Sucrose .77.................s....– Water.....................1..........0 g 1...........0 g 82..............8........................................... 2.......5.......... I....... 1 No...... Properties of the suspensions No...very low Sedimentation after 2 weeks: .......0 g 3.........3.0 g III..........................................6 g – 5.....................2 g Chocolate flavour ................. 2 Colour:...........4 g q...................................not observed Redispersibility after 2 months: ........0 g Lutrol F 127 or Lutrol F 68 [1]...................................... 1 No.... 3.

................... cool and sterilize...... heat......0....0 g g g g g g g g 2..2 Sodium sulfite or cysteine ................ BASF Fine Chemicals Generic Drug Formulations 1998 . add the active ingredients and stir until they are dissolved.................. 3.4 Propylene glycol Pharma [1] .10.0 Trimethoprim ........... Manufacturing Dissolve Kollidon. Formulation Sulfamoxole ...0 Parabene .10......................4................ 4.... Remark The use of sodium sulfite in injectables is not allowed in all countries.........8 Liquid Formulations (Lab scale) Sulfamoxole + Trimethoprim Veterinary Injectable Solution (400 mg + 80 mg/10 ml) 1...0.. Properties of the solution A clear solution was obtained........ Add ethanol.............................................8 Kollidon 12 PF [1] .... sodium sulfite (or cysteine) in the mixture of water und propylene glycol......0 Water for injectables ...30..................5............... parabene............................................0...44.....................6 Ethanol ........

.................................250 g Lactose monohydrate [8] ............................................................9 Tablet formulations (Lab Scale) Sulfathiazole Tablets (250 mg) 1.........2 – 3 g 250 g – 237 g 12 g q.12 g II.....................................0.............................2.... pass through a 0... Formulations No................s...... Kollidon CL [1] ...... 1 No. 3....................2 % Dissolution... 2.. 12 g 2–3 g I...115 N Disintegration ..........2 % 69 % 90 % BASF Fine Chemicals Generic Drug Formulations 1998 .......biplanar Hardness .............................................................. Tablet properties Weight .12 mm Form ...237 g Dicalcium phosphate [9] .......................q............................................................s............ Water ........504 mg Diameter ................... Manufacturing (Wet granulation) Granulate mixture I with solvent II.......... dry.............................................80 % 20 min ................ 10 min .................................................................... 2 Sulfathiazole ...................1 min Friability ........................ add III and press with low compression force................................– Kollidon 30 [1] ...12 g Magnesium stearate [2] ........ III.....96 % 512 mg 12 mm biplanar 154 N < 1 min 0...8 mm sieve...................................................

................8 Kollidon 12 PF or Kollidon 17 PF [1] ....................100....................... Manufacturing Dissolve Kollidon and sulfathiazole at 70 °C in water and cool slowly to room temperature.......8 Liquid Formulations (Lab scale) Sulfathiazole Veterinary Injectable Solution (8 mg/ml) 1..< 0......0 g g g g 2............. Formulation Sulfathiazole ....... Sterilisation can be done by filtration through a 0..........very low 4.1 Water for injectables .........12.. Remarks A preservative can be added if needed..............2 to 0.....clear Viscosity............. To prevent of discolouration of Kollidon in the solution during storage 0.................. BASF Fine Chemicals Generic Drug Formulations 1998 ...... 3.2 filter..........5 Sodium sulfite ....... Properties of the solution Appearance ...0.........5 % of cysteine could be added as antioxidant instead of sodium sulfite...........5..................

.................02 % sodium bisulfite or 0........low 4..................................... Water ..8 g Kollidon 25 [1] ........ Formulation Sulfathiazole ... Properties of the solution Appearance .............100........ Remark An antioxidant to stabilize the colour of solution could be added (0....................s.0 ml 2.................0... BASF Fine Chemicals Generic Drug Formulations 1998 ....................5.......clear Viscosity......22........8 Liquid Formulations (Lab scale) Sulfathiazole Veterinary Oral Solution (8 mg/ml) 1................ Manufacturing Dissolve Kollidon 25 and Sulfathiazole at 70 °C in water and cool slowly to room temperature.5 g Preservative ............ 3..................................5 % cysteine).....q................................................

... pass the solids through a 0.......................................3 g g g g g g g 2................................0 Water ......................0..0 II...........2............323 mg Diameter ....0 Talc [10] .......................... Tablet properties Weight ..........0.................................230................................................ Kollidon CL [1]........12 mm Form ... Tannic acid... Manufacturing Prepare solution I......... 3........8 mm sieve and dry............. Add the components III and press with low compression force...............33..............................0 III......................40 N Disintegration .......... Wash with water until the water is clear..........3 Calcium arachinate [2] .........................6 Aerosil 200 [4] ......55.........230............. suspend II and filtrate the formed insoluble tannincrospovidone complex..0....2........... Formulation I.................................................................8 % BASF Fine Chemicals Generic Drug Formulations 1998 .................biplanar Hardness..................9 Tablet formulations (Lab Scale) Tannin-Crospovidone Complex Tablets (55 mg + 230 mg) 1............< 1 min Friability............................... Avicel PH 101 [5] .................

....................... Tablet properties Weight .........................1..............0 g 1.... mix intensively and press with low compression force (10 kN)............... BASF Fine Chemicals Generic Drug Formulations 1998 ..............................98....................1...........................................5 min Friability................. 3.... 5 min ....8 mm sieve.............1 g Ludipress [1] ...0 g 2...............0. Formulations 1 mg 5 mg Terazosin hydrochloride (Knoll) .........6 mg 6 mm 105 N 5 min < 0...................................59 % 10 min ..................9 Tablet formulations (Lab Scale) Terazosin Tablets (1 mg and 5 mg) 1............98................6 mm Hardness ................97 % 20 min ..........0 g Magnesium stearate [2] .. Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation.....5 g 94.....................................0 g 5....94 N Disintegration ......1% 41% 97 % 100 % 4....100 % 97............. Manufacturing (Direct compression) Pass all components through a 0............................1% Dissolution.......2.......................................1 mg Diameter ..............

.... Manufacturing Dissolve Lutrol F 127 and Cremophor RH 40 in water at 40 °C.....0 g Cremophor RH 40 [1] .....2 %) 1........92....3.........5................... 3.................... Whilst stirring slowly add the terfenadine............................. Water...3.....2 g 2... BASF Fine Chemicals Generic Drug Formulations 1998 ........ Physical stability After 7 days of storage at room temperature almost no sedimentation of the terfenadine was observed but the redispersibility by shaking (2 times) was very easy....s........ Formulation Terfenadine .........................8 Liquid Formulations (Lab scale) Terfenadine Suspension (60 mg/5 ml = 1....q..... Properties of the suspension A tasteless milky suspension was obtained...2 g Lutrol F 127 [1] .....6 g Preservative .................................................. 4..1.......

.......5 min Friability ...............................6 Magnesium stearate [2]....2..........biplanar Hardness .... 3.....................................8 mm sieve and press with very low compressive force.........235 Kollidon CL [1]...............1 mg mg mg mg 2.................< 0.....183 N Disintegration ....... Manufacturing (Direct compression) Mix all components......1% BASF Fine Chemicals Generic Drug Formulations 1998 ................................................ pass through a 0...................................................................8 mm Form ...........301 mg Diameter ........9 Tablet formulations (Lab Scale) Terfenadine Tablets (60 mg) 1....................... Tablet properties Weight ................................................................................................... Formulation Terfenadine .....60 Ludipress [1] .....................................

3 g g g g 2..........63 N Disintegration..............................8 mm Form .125 Ludipress [1] . Physical stability (12 months...biplanar Hardness...........9 Tablet formulations (Lab Scale) Tetracycline Tablets (125 mg) 1.......................................................................1 – 2 min Friability ....................1 – 2 min Friability ..................42 Magnesium stearate [2] .... 20–25 °C) Weight ............................................ 3......biplanar Hardness.......... Tablet properties Weight .................... Formulation Tetracycline hydrochloride (Welding) ................8 mm sieve and press to tablets with very low compression force....100 Avicel PH 101 [5] ...........................< 0........................................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ......................1% 4..........2............................................................................................< 0................64 N Disintegration.................................................................278 mg Diameter ................... pass through a 0...............8 mm Form ............................................................................................ Manufacturing (Direct compression) Mix all components...........278 mg Diameter ..........

............0 g Talc [10] .................biplanar Hardness........2.....................5 g 2.....................5 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............0 g Kollidon CL [1]........................3 min Friability......0 g Kollidon 30 [1] ................0 g Aerosil 200 [4] ....... Formulation I......................... Manufacturing (Direct compression) Pass the components I through a 0.. II........... add the mixture II and press with low compression force......9 Tablet formulations (Lab Scale) Tetracycline Tablets (250 mg) 1...........62 N Disintegration ...0 g Lactose monohydrate D 20 [8].........28.................................0.....................250....................15.........................175.....................25.......5 mm sieve.....................3........................ Tetracycline hydrochloride ...............................12 mm Form ................505 mg Diameter . Tablet properties Weight .................................................................5 g Calcium arachinate [2] .................... 3............3..............

....................1 – 2 min Friability.......106 N Disintegration.................................................................. Manufacturing (Direct compression) Pass the components through a 0.......................................208 mg Diameter .............................................................113 Starch 1500 (Colorcon) ..................0.........................5 Magnesium stearate [2] ...............5 mm sieve and press with low compression force...........................2 g g g g g 2..................50 Avicel PH 101 [5]..................................... Tablet properties Weight .8 mm Form ................2 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................................................................2......30 Kollidon VA 64 [1] . Formulation Tetrazepam ... 3...............biplanar Hardness .................9 Tablet formulations (Lab Scale) Tetrazepam Tablets (50 mg) 1...................

......................4 mm (Knoll) .............................................141 N Disintegration ............2 Magnesium stearate [2] ....................... pass through a sieve and press with very low compression force.....0...............................................9 Tablet formulations (Lab Scale) Theophylline + Ephedrine Tablets (130 mg + 15 mg) 1... Tablet properties Weight .2 g g g g g 2..................... Manufacturing (Direct compression) Mix all components..97 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................................150 Aerosil 200 [4] ........... 3...................130 Ephedrine hydrochloride (Knoll) .................1% Dissolution of Theophylline 15 min .45 % 30 min .................................15 Ludipress [1] ....85 % 60 min .................. Formulation Theophylline 0..........biplanar Hardness ..................................8 mm Form ..............9 min Friability ....2...............302 mg Diameter ...................................................................................1/0...........

......83 N Disintegration ............100 g Ludipress [1] ...........................2 min Friability ..................................biplanar Hardness................. Formulation Theophylline 0...................... 3......247 mg Diameter ...15 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................. Manufacturing (Direct compression) Mix all components.9 Tablet formulations (Lab Scale) Theophylline Tablets (100 mg) 1...1/0..............8 mm Form ........2....................0...............................................................4 mm (Knoll) ............3 g 2.......147 g Magnesium stearate [2] ...................................... Tablet properties Weight ............................... pass through a sieve and press with low compression force....................................

... 4.................. BASF Fine Chemicals Generic Drug Formulations 1998 ........8 Liquid Formulations (Lab scale) Theophylline Injectable Solution (200 mg/5 ml) 1...................5.......15 g Propylene glycol Pharma [1] ......2 g Kollidon 12 PF [1] ...................2 and did not recrystallize in a short term test... Water for injectables ..5 % of cysteine could be added as antioxidant.........2 to 0. Antioxidant...q........ Properties of the solution The obtained clear and somewhat yellowish solution had got the pH value 5..................ad 50 g 2..................................s......q.............s.......... Remarks To prevent of discolouration of Kollidon in the solution during storage 0.............................. Formulation Theophylline (Knoll) ............... Manufacturing Dissolve Kollidon 12 PF and the preservative/antioxidant in water and add theophylline to the well stirred solution 3..10 g Preservative ....

...1 g II.......0 g Butylhydroytoluene ...... Maintain cool until the air bubbles escaped....... 5.......................5....................... Heat to about 50 °C and dissolve about 14 g of III in the combined solution I/II.6. Tretinoin (BASF).0.. dark) 0 Months Tretinoin content 100 % 6 Months 12 Months 100 % 96 % There was no loss of alpha bisabolol during these 12 months..0 g Cremophor RH 40 [1] ..70..... Chemical stability (20–25 °C.............05 g Lutrol E 400 [1]....... Lutrol F 127 [1] ....04 g (-)alpha-Bisabolol...............0......... BASF Fine Chemicals Generic Drug Formulations 1998 ........ Remark It is important to protect this formulation against light to avoid the isomerization and degradation of tretinoin...5 g 2......... 4........... Cool to about 6 °C and dissolve the rest of III..... 3....... Water.7 Formulations of semi-solid drugs (Lab scale) Tretinoin + Alpha Bisabolol Gel (50 mg + 100 mg/100 g) 1............s............3 g Preservatives.................. natural (BASF) . Formulation I.......0.......q................ Properties of the gel A clear yellowish gel was obtained..................... III...18............ Manufacturing Add solution II slowly to the clear solution I at about 40 °C......................................6.

......... 4.................................. 3...6...... Manufacturing Add II slowly to the clear solution I at about 40 °C..500 mg/100 g) 1.6........ dark) Tretinoin Dexpanthenol 96 % 100 % 5........ Water.................... Remark It is important to protect the gel against light to avoid the isomerization and degradation of tretinoin........0 mg Lutrol E 400 [1].......2.68........... Lutrol F 127 [1] ...... Chemical stability (12 months.7 Formulations of semi-solid drugs (Lab scale) Tretinoin + Dexpanthenol Gel (50 mg + 2.............................................................4 g Dexpanthenol (BASF).0 g Butylhydroytoluene ...50.......0 g 2........5.. Cool to about 6 °C and dissolve the rest of III................. Tretinoin (BASF) .5 g III............ Formulation I.18. Properties of the gel A clear yellowish gel was obtained... BASF Fine Chemicals Generic Drug Formulations 1998 ............... 23 °C.40 mg II............ Maintain cool until the air bubbles escaped..........0 g Cremophor RH 40 [1] ....... Heat to about 50 °C and dissolve about 4 g of III in I/II..

.480) BASF Fine Chemicals Generic Drug Formulations 1998 ..8... Manufacturing Separately prepare solution I and mixture II by heating to about 75 °C..0.......... 3.............5 Glycerol monostearate .2 g g g g g g g g g g g g 2....5 Perfumes .. Tretinoin (BASF)....... To the warm mixture II add solution I....05 Luvitol EHO [1] ....................... dark) Months Tretinoin content Loss of tretinoin 0 3 6 9 12 0..........4.......................... then mixture III and cool by stirring........047 % 0.................0..........7 Formulations of semi-solid drugs (Lab scale) Tretinoin Cream (50 mg/100 g) 1..........04 Propylene glycol Pharma [1] ........0....0 Tegiloxan ® 100 (Goldschmidt) .......76. Butylhydroxytoluene .....046 % 0....... Heat mixture III until a clear solution is formed.......0 Cremophor A 25 [1] .......... Formulation I.............................................................6..................0..... Chemical stability (20–25 °C........ Cremophor A 6 [1] ............0 Preservatives ...........3........3.......................................047 % 0% 0% 0% 0% Analytical method: Spectrophotometric at 358 nm in chloroform + 2-propanol 1+1 (E 1%/1 cm = 1...........0..........................3....................2 Water...1.....................0 Cetyl alcohol .....0 II.............046 % 0.....047 % 0.5 III..

Remark It is important to protect the gel against light to avoid the isomerizationand degradation of tretinoin.4. BASF Fine Chemicals Generic Drug Formulations 1998 .

.0 g Cremophor RH 40 [1] ....0.......0....0 g III........... Butylhydroxytoluene ............ Triethanolamine ......0 g Perfume ......... Manufacturing Prepare suspension II and add solution III to the well stirred suspension......... dark) No loss of tretinoin was measured after 1 year..................................04 g II..5 g Water.15.6. 5.........6 g 2.........................s. Tretinoin (BASF)................................... Carbopol® 940 (Goodrich) ..........q..............6............................... Formulation I..................................1.... Remark It is important to protect the gel against light to avoid the isomerization and degradation of tretinoin...........7 Formulations of semi-solid drugs (Lab scale) Tretinoin Gel (50 mg/100 g) 1................................05 g Ethanol .. Properties A clear yellowish gel was obtained..... 3.......................... BASF Fine Chemicals Generic Drug Formulations 1998 .......76....... Chemical stability (20–25 °C....... 4......7 g Water........ When a clear mixture is formed add solution I....0....0................

........046 % 0....................05 g Cremophor RH 40 [1] .5.....046 % = 100 % 0............... Introduce this warm solution slowly in solution II....0..0 g Propylene glycol Pharma [1] .........044 % 0.......... BASF Fine Chemicals Generic Drug Formulations 1998 ...................0 g Butylhydroxytoluene ...... 3............ II....s.......... Formulation I..........8 Liquid Formulations (Lab scale) Tretinoin Solution (50 mg/100 g) 1...70..1 g Water... (BASF)........05 g Alpha Bisabolol nat.......q........................ Chemical stability (20–25 °C............ Remark It is very important to protect this formulation from light to avoid the isomerization and degradation of tretinoin..14. It forms a clear yellow solution... 2..15....... 4...............0......0. Tretinoin (BASF)...045 % 0.. Properties of the solution Clear yellow liquid.....0 g Parabenes/sorbic acid .044 % = 96 % 5.. protected from light) Months Tretinoin content 0 3 6 9 12 0... Manufacturing Heat mixture I to 40 – 50 °C to obtain a clear solution.........

........ Manufacturing (Direct compression) Mix all components..................4 Ludipress [1] ..........................................45 N Disintegration .... Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation........... pass through a sieve and press with low compression force......................................206 mg Diameter ..2 % 4...................................8 mm Form ...................biplanar Hardness....... 3................... Formulation Triamcinolone.........2..... Tablet properties Weight ........................................................2 Magnesium stearate [2] ...................................................................................9 Tablet formulations (Lab Scale) Triamcinolone Tablets (4 mg) 1.0..............2 min Friability...............2 g g g g 2................... BASF Fine Chemicals Generic Drug Formulations 1998 ................191 Kollidon CL [1] .............................................

....3 min Friability .......2........ Manufacturing (Direct compression) Mix all components....... BASF Fine Chemicals Generic Drug Formulations 1998 ......................0........ Remark If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation..194 g Magnesium stearate [2] ...........biplanar Hardness.... Formulation Trifluoperazine hydrochloride........1 g 2..................................9 Tablet formulations (Lab Scale) Trifluoperazine Tablets (5 mg) 1...........................8 mm Form .. Tablet properties Weight ....................................204 mg Diameter .....................15 % 4............................................. 3............65 N Disintegration ....................................... pass through a sieve and press with very low compression force......................5 g Ludipress [1] ...............................................................................

..0....... Sodium hydroxide solution 10 % .....75...... 3...................20..7 Formulations of semi-solid drugs (Lab scale) Ultrasonic Adhesive Gel 1.4 g II....... Preservative (e......5 g Water..... Kollidon 30 [1] ............g....2...............................0.. Carbopol® 940 (Goodrich) .......................... Properties of the gel A clear colourless adhesive gel was obtained..... 4.0 g 2....6 g III. Formulation I...1...........6............. BASF Fine Chemicals Generic Drug Formulations 1998 ......................... Manufacturing Prepare solution I by heating and add II slowly to obtain a homogeneous suspension....... Add the solutions III and IV....... Parabenes) ...0 g IV... Remark The addition of salts like sodium chloride would be possible but the consistency could be changed by such modification..5 g Water..........

...........10 min Friability...................................................................................................0 Avicel PH 101 [5] ............................................3 g g g g g g 2.......120.................. Tablet properties Weight .......................................44.....36. 3...3.7. mix and press with low compression force.............9 Tablet formulations (Lab Scale) Valeriana Extract + Passiflora Extract Tablet Cores (44 mg + 30 mg) 1.3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............................................6 Magnesium stearate [2]...............................11.... powder..biconvex Hardness........... powder........8 mm sieve........231 mg Diameter ........9 mm Form ....................... Manufacturing (Direct compression) Pass all components through a 0... Formulation Valeriana extract........0 Aerosil 200 [4] .........0 Kollidon CL [1] ...............49 N Disintegration..0 Passiflora extract..............................2...............................0................

..........162 N Disintegration .............. BASF Fine Chemicals Generic Drug Formulations 1998 ............12 mm Form ....................1% 4.....................................................20 g Isopropanol .............................................0................. Remark The powder mixture was electrostatic.... Tablet properties Weight ............................................................................60 ml III....................607 mg Diameter ....................7 min Friability ..............................2........9 Tablet formulations (Lab Scale) Valproate Sodium Tablets (500 mg) 1. Manufacturing (Wet granulation) Granulate mixture I with solution II..........80 g II.......5 g 2............ mix the dry granules with III and press with low compression force...............................5 g Magnesium stearate [2] ................................. 3..... Formulation I....................... pass through a sieve.................500 g Corn starch [3] .................. Valproate sodium.......................... Kollidon CL [1] ..biplanar Hardness ...................... Kollidon 30 [1] ........

.....................................2.............. Tablet properties Weight .............4 % 4.......................9 Tablet formulations (Lab Scale) Verapamil Tablets (120 mg) 1................... Remark The tablet weight should be increased to about 400 mg.................................................374 mg Diameter ................. pass through a 0......................3 Aerosil 200 [4] ...............108 N Disintegration.......12 mm Form ..............................5 – 6 min Friability...... Manufacturing (Direct compression) Mix all components.............120 Ludipress [1] .................... Formulation Verapamil hydrochloride ........ 3............................... BASF Fine Chemicals Generic Drug Formulations 1998 .....................................................8 mm sieve and press with medium compression force...................biplanar Hardness .....3 g g g g 2.....270 Magnesium stearate [2] ..............0.....................

..................8 mm sieve........ Tablet properties Weight ............/g (BASF) Pyridoxine hydrochloride (BASF).......000 i.....9 Tablet formulations (Lab Scale) Vitamin A + Vitamin B6 + Vitamin E Tablets (40..000 i........... mix and press with high compression force...80 g 500.....12 mm Form ..................................................................5 g 2.395 g Magnesium stearate [2] ................. 3............. + 40 mg + 35 mg) 1........ Manufacturing (Direct compression) Pass all components through a 0..........................75 g (BASF) Ludipress [1] ..................... Formulation Vitamin A acetate dry powder ..................................................13 min Friability ........< 0............2.......89 N Disintegration...................... u..biplanar Hardness...........................................4 g Aerosil 200 [4] ..................... u.................1% BASF Fine Chemicals Generic Drug Formulations 1998 .........40 g Vitamin E acetate dry powder SD 50 .........................................583 mg Diameter ...........

...........2..........................290 mg Diameter ............... u.........9 Tablet formulations (Lab Scale) Vitamin A + Vitamin C + Vitamin D3 Chewable Tablets for Children (2.......1... u./g (BASF) Ascorbic acid......0 g Ludipress [1] .....300................ 3.......20.......30.............5... u...0 g Mannitol ..30....................................000 i... powder (BASF) ................107 N Disintegration ..8 mm sieve.................... powder [6].....................33.......1 g Cyclamate sodium .........) 1.............0 g 500... + 30 mg + 200 i.......000 i..biplanar Hardness ..............................................0 g Sucrose............. crystalline......0......0 g 2.. mix and press with high compression force.......................0 g Flavour mixture (Firmenich)..0 g Stearic acid [7] .........0 g Polyethylene glycol 6000.7 min Friability......................................................0................................... Tablet properties Weight ....... Manufacturing (Direct compression) Pass all components through a 0.......000 + 50. crystalline [10] ...............300.........................16 mm Form ...............................0 g Sorbitol......300...........................300...............4 % BASF Fine Chemicals Generic Drug Formulations 1998 .............4............0 g Saccharin sodium ..... Formulation Vitamin A + D 3 dry powder .........

.............. 3.....8 mm sieve.................... powder (BASF)... 2 Weight ....... + 60 mg + 30 mg) 1.... 1 No............................... Formulations No......60............................................2................................1% 279 mg 8 mm biplanar 67 N 6 min < 0..............53 N Disintegration ... 1 No.........0 g Aerosil 200 [4] .. mix and press with medium compression force. u.1............0 g 2...0 g 2......0 g 100............20......................0 g – 30................................– Kollidon CL [1] ...30...............4 g 60............biplanar Hardness ........8 mm Form ...........285 mg Diameter ......000 i........15 min Friability ....................................0 g Avicel PH 101 [5] .................– Talc [10] .........................0 g – 20.4 g 500................0 g Kollidon VA 64 [1]..............................................– Lactose monohydrate [8] ..............0 g 1.......< 0...... Tablet properties No.............................0 g Kollidon 25 [1] .......................0 g Mannitol ............................./g (BASF) Ascorbic acid..2...........9 Tablet formulations (Lab Scale) Vitamin A + Vitamin C + Vitamin E Tablets (1......0 g 5..... u...................0 g 60.........0 g 5...............................1% BASF Fine Chemicals Generic Drug Formulations 1998 ..............................60... 2 Vitamin A acetate dry powder ............105........................200 i.0 g Vitamin E acetate dry powder 50 % ...........5...................... Manufacturing (Direct compression) Pass all components through a 0..........

Properties of the solutions A clear yellow solution was obtained....) 1.......7 Mio i...5../g (BASF) ...... 5.1 g Magnesium sulfate .. to eliminate any separation of the phases that may have occurred.u...... 3... Sterilization can also be performed by membrane filtration under pressure.. After the ampoules have been heat-sterilized.. they should be shaken for a short time... u... Remark Perhaps it would be recommendable to use an other magnesium salt instead of the sulfate to avoid any precipitation of calcium sulfate during storage....... i...2... Formulation I..1.........85..000 i...000 i.0 g II..0 g III... Calcium gluconate ..............u..... u....... u.... Vitamin A palmitate 1./g 15 mg Solutol HS 15 [1]........ protected from light) No change of the clarity after some days.............. + 100 mg + 200 mg/g i. BASF Fine Chemicals Generic Drug Formulations 1998 .. while they are still hot....8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Calcium + Magnesium Injectable Solution (33... Add the water very slowly to the well stirred mixture I.13...... Physical stability (20–25 °C. Manufacturing Heat mixture I and the water (II) separated to about 65 °C..... Water for injectables . + 6...0 g 2..0 g Vitamin D 3 (Cholecalciferol) 40 Mio..... Cool to room temperature and dissolve the components III... 4.....1.......

. When the temperature is reached add the beta-carotene IV........ Properties of the solution Dark red-brown...................... Heat the water II to 65 °C and add it slowly to the heated mixture I.4 2.0 II..0.. + 10 mg + 8 mg/g) 1....... Formulation I..... clear solution... Manufacturing Heat mixture I to 65 °C...< 9......................u.........4 Cremophor EL [1]. Let cool under continuous stirring of about 30 minutes..1... Vitamin E acetate .8 g g g g g g g g g 2.u.... BASF Fine Chemicals Generic Drug Formulations 1998 ..........5 Mio i...... Sterilization can also be performed by membrane filtration under pressure......u. A clear solution is formed...............4.. Beta-Carotene crystalline (BASF)...0......000 i..0 Butylhydroxytoluene ..... Remark In Germany Cremophor EL must be declared on the package of injectables.../g (BASF) Vitamin D 3 40 Mio i.....05 Benzyl alcohol ............0 IV.. hold for 3 min at this temperature and then add Mixture I/II slowly during the next 4 minutes.... to eliminate any separation of the phases that may have occurred...... Water for injectables ..........1........... After the ampoules have been heat-sterilized....../g ..72. + 20.....0........................3 III... Vitamin A propionate .............. 4...........5.................0 Cremophor EL [1] ...u............. A clear solution is formed (= Mixture I/II).. Heat the mixture III to 180 °C....8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E + Beta Carotene Veterinary Injectable Solution (100..... they should be shaken for a short time.. while they are still hot..9.....000 i.. 3.....

.......0......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Aqueous Injectable Emulsion for Cattles (500..... and then add the water (60 °C) slowly and with vigorous stirring...... while they are still hot... butylhydroxytoluene and benzyl alcohol at approx......2 g Vitamin E acetate (BASF) .... u......... 60 °C....... 3..... Physical stability (20–25 °C................. BASF Fine Chemicals Generic Drug Formulations 1998 .5 g Solutol HS 15 [1]. pale yellow emulsion.1..ad 100 ml 2......../g (BASF) Vitamin D3 40 Mio............ Viscosity: Less than 20 mPa · s 4............ to eliminate any separation of the phases that may have occurred.... – After the ampoules have been heat-sterilized.... protected from light) No change of the appearance during 2 years. u.....5 Mio i................ + 50 mg/ml with Solutol HS 15) 1..u......5. Manufacturing Mix the vitamins.....0......... Properties of the emulsion Aspect: Milky........ Sterilization can also be performed by membrane filtration under pressure......5..000 i.... Solutol HS 15..0 g Water for injectables ... Formulation Vitamin A propionate ....0 g 2... they should be shaken for a short time......... + 75./g ....000 i....u...0 g Benzyl alcohol .....5 g Butylhydroxytoluene . i....................15..22...........

protected from light) i.5.000 = 20–25 °C = 6 °C 500. 16 % loss after 2 years. 700. u. Chemical stability of vitamin A (2 years.000 400./g Room temperature: 9 % loss after 1 year.000 600.000 0 3 6 9 BASF Fine Chemicals Generic Drug Formulations 1998 12 Months 15 18 21 24 .

+ 75.0..........1.... + 50 mg/ml with Cremophor EL) 1..... u.. and water at 60 °C is slowly incorporated with vigorous stirring..........5......ad 100 ml 2......000 i.000 i. Chemical stability of vitamin A (Stress test at 40°C) Vitamin A content 1 Month 2 Months 3 Months 92 % 86 % 81% 5..... to eliminate any separation of the phases.......0 g Butylhydroxytoluene .0....................... Properties of the emulsion Pale yellow milky....22..8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Aqueous Injectable Emulsion for Cattles (500........ they should be briefly shaken whilst they are still hot.................... 4. Cremophor EL.....0 g Water for injectables .....0 g 2.... BASF Fine Chemicals Generic Drug Formulations 1998 ...... Remark In Germany Cremophor EL must be declared on the package of injectables..... After the ampoules have been sterilized..10....u...5 g Benzyl alcohol .......u...../g (BASF) Vitamin D 3 (Cholecalciferol) .2 g Vitamin E acetate (BASF) .......5............. Manufacturing The vitamins..5 Mio i.....0 g Cremophor EL [1] ........... stable emulsion with a viscosity of less than 30 mPa · s.... 3............ butylhydroxytoluene and benzyl alcohol are mixed together at around 60 °C... Formulation Vitamin A propionate ..........................

Vitamin A found in the liver [%] 6. Bioavailability of vitamin A in broilers after 7 days (intramuscular application) 80 60 40 20 0 Aqueous emulsion Organic solution for comparison BASF Fine Chemicals Generic Drug Formulations 1998 Oily solution for comparison .

...................................8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Concentrates.. 1 No......./g ...20 g Butylhydroxytoluene .– (BASF) Vitamin D 3 40 Mio i.0 g Glycerol .......... Clarity: Formulation No....50 g Preservative ... u... miscible with water..06 g 29./g ...u./g ...06 g Cremophor EL [1] ........u...... Water-miscible (120.........u.50 g q.......4............ u.7.ad 100 ml – 4....................30... clear viscous liquids.....80 g 0... 2: 28 FTU 32 FTU BASF Fine Chemicals Generic Drug Formulations 1998 ....... II... 2 Vitamin A palmitate 1..7 Mio........5 Mio i......... Manufacturing Heat mixture I to about 65 °C..15 g 4. Properties of the solutions Yellow... ad 100 ml 2........... i.5........................... 3........................0............000 i.10 g (BASF) Vitamin A propionate 2....0.... Water ...0 g 6........s....... Formulations I............q...6... + 60.......s.. stir well and add very slowly the warm solution II (65 °C)...........000 i............20 g 0........... + 40 mg/ml) 1.... 1: Formulation No....... No.....15 g Vitamin E acetate (BASF) ........

...... Remark In Germany Cremophor EL must be declared on the package of injectables..5 Cremophor EL [1] .................. 4.....35.....u............/g in arachis oil........ + 50 mg/ml) 1..2..u... 3..5.....10. + 75.u...........5 DL-alpha Tocopherol (BASF) ...............0 1.......5 Miglyol ® 812 (Dynamit-Nobel) ..1.........0...2.......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Injectable Solution in Organic Solvents for Cattles (500.....5...000 i.......... Chemical stability (stress test at 40 °C) 3 – 4 % loss of vitamin A per month...........7 Benzyl alcohol ..... BASF Fine Chemicals Generic Drug Formulations 1998 .........4.. Manufacturing Mix all components at about 60 °C and cool................/g (BASF) Vitamin D 3 2.........................5 Vitamin E acetate (BASF) ....8 g g g g g g g g g 2...37.. Properties of the solution Yellow clear liquid..7 Mio i...0 Mio i............... 5.. Formulation Vitamin A palmitate.....000 i....0 Benzyl benzoate .............u...............5 Butylhydroxyanisole ........

.....0 Water for injectables ..u...0 Butylhydroxytoluene .. Formulation I II......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Veterinary Injectable Solution (100... If the obtained yellow solution is not completely clear heat for some minutes more at 65 °C..4.............................. Remark In Germany Cremophor EL must be declared on the package of injectables............../g (BASF) Vitamin D3 40 Mio i.< 15......4 Benzyl alcohol .......000 i........ 4..............u.. 3.....1 g g g g g g g 2............ Sterilization can also be performed by membrane filtration under pressure.......5................ Heat the water II to 65 °C separately and add it very slowly to the well stirred mixture I.. yellow liquid of low viscosity..... while they are still hot........ Properties of the solution Clear. they should be shaken for a short time......u......5 Mio i........78.... After the ampoules have been heat-sterilized..4 2.. to eliminate any separation of the phases that may have occurred..................0......05 Vitamin E acetate ....000 i..........1....1.. Vitamin A propionate ..u.. + 10 mg/g) 1..0 Cremophor EL [1] ......0. + 20... Manufacturing Mix the components I and heat to 65 °C......../g.... BASF Fine Chemicals Generic Drug Formulations 1998 ........

Water ..0. Formulation Vitamin A palmitate........ also heated to 65°C.....67...................... Properties of the concentrate Clarity: Density (25°C): Viscosity (25°C): Clear (27 FTU) 1....7 Mio.....6..../g (BASF) Vitamin D 3 40 Mio...... i...... u..................q. u.................... Water-miscible (100....../g ... u.. BASF Fine Chemicals Generic Drug Formulations 1998 .../D3/ml) 1..........................2 g 2............3 g Cremophor RH 40 [1].000 i.............014 g/ml 25 mPa · s The concentrate is miscible with water and can be processed further to liquid pharmaceuticals........... Add very slowly the solution of the preservative in water......0 g Preservative ............8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Concentrate.. with vigorous stirring........ i. u..... 3....../A + 20..........000 i.. Manufacturing Mix the vitamins and the antioxidant with Cremophor RH 40 at 65 °C....55 mg Butylhydroxytoluene ..26....5 g 1......s....5..

...............7........... Water .. BASF Fine Chemicals Generic Drug Formulations 1998 .... Properties of the solution Slightly opalescent.....u....../g ..../g (BASF) Vitamin D 3 40 Mio i.q...... stir well and add very slowly the warm solution II (65 °C)..........u.......u.10 g 1.... u...........0. II.....15 g Cremophor RH 40 [1]......25.7 Mio i..................5..........0 g 2... yellow liquid.......... Water-miscible (120........ 3..03 g Butylhydroxytoluene........ad 100.....s....... Formulation I............ Manufacturing Heat the mixture I to about 65 °C........... miscible with water (Clarity: 34 FTU)................... A + 12......000 i....0 g Preservative ......000 i. Vitamin A palmitate .0.......... D/g) 1...8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Concentrate.

...... Properties of the solution Yellow clear or slightly opalescent liquid....8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Drops (30...000 i...............74..................3 g Lutrol E 400 [1] ..........7.....0.8 g 2...0.u...... Manufacturing Heat mixture I and solution II to about 65 °C and add II slowly to the well stirred mixture I...0 g Butylhydroxytoluene .. Vitamin A palmitate.......000 i..8 g Sorbic acid ....10... BASF Fine Chemicals Generic Drug Formulations 1998 .2 g Water.........5 mg Cremophor RH 40 [1] ... u............/g (BASF) Vitamin D 3 40 Mio......u......7 Mio i.....0 g Parabene ........... u..................... + 3................5............/g ................. i..0............/g) 1......... II............12................................ 3......9 g 1......................1.. Formulation ............................

Chemical stability of vitamin A (about 23 °C) 30.000 0 0 3 BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 9 12 .000 25.000 88% 84% 20.i./g 4. u.

..1......026 g 0.... BASF Fine Chemicals Generic Drug Formulations 1998 ...000 or 10...........u.u........013 g Butylhydroxytoluene.../g (BASF) Vitamin D 3 40 Mio i. D3/ml) 1.u.000 i... 3. to eliminate any separation of the phases that may have occured..... Properties of the solutions Clear yellow solutions where obtained.1 g Solutol HS 15 [1] ....... while they are still hot....0.......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Injectable Solutions (30. Manufacturing Heat the mixture of the vitamins with butylhydroxytoluene and Solutol HS 15 to about 65 °C......000 i.............s.... Water for injectables ... Formulation 30. A + 5....0 g q... D 3 30..000 i...000 i.... D 3 Vitamin A palmitate .1 g 10... protected from light) No change was observed during 1 year...u.........000 i.........../g ..9....9 g 0. After the ampoules have been heat-sterilized.q.... Heat the solution of the preservative in water to the same temperature and add it slowly to the well stirred vitamin mixture.. A + 10.. ad 100 ml 2....u.0 –10.... 4. A + 5....000 i.s.. they should be shaken for a short time.....u.ad 100 ml 1. Sterilization can also be performed by membrane filtration under pressure..............0 g Preservative .........7 Mio i. Physical stability (20–25 °C.5........u..9 g 1.u.0.

..........0 g Preservative ......... BASF Fine Chemicals Generic Drug Formulations 1998 ..... yellow liquid....... Flavour ..60............... 4..............0.... II..............000 i..q.......u......../g (BASF) Vitamin D 3 40 Mio i.....8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Oral Solution for Children (1......................s./g ...... + 100 i.....s... 3.........................u.......0........5..0 mg 1..ad 100 ml 2...... Manufacturing Heat mixture I to about 65 °C.. Water................... Vitamin A palmitate .u............3 mg Butylhydroxytoluene ..3.... stir well and add slowly the hot solution II (65 °C).2 mg Cremophor EL or Cremophor RH 40 [1] .q............. /ml) 1.........7 Mio i...... Formulation I.... Physical stability (20–25 °C) No change of appearance after 2 weeks.....u. Properties of the solution Clear.

............ Manufacturing Heat mixture I to about 45 °C......... /ml) 1.5................ 4...... pH 6........... Properties of the syrup Clear.0 g Sugar syrup 50 % ...7...... yellow liquid...........8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Syrup (30..2.. stir well and add slowly the syrup II....... II......... Vitamin A palmitate.....u./g (BASF) Vitamin D 3 40 Mio i..9 g 1............ Formulation I......1. 3./g .25 mg Cremophor RH 40 ...7 Mio i..u...000 i.000 i... + 10..ad 100 ml 2..u...... Chemical stability of vitamin A (20-25 °C) Vitamin content After production 3 Months 6 Months 100 % 99 % 97 % BASF Fine Chemicals Generic Drug Formulations 1998 ...u...

Formulation Vitamin A acetate dry powder . powder [6] .....1% BASF Fine Chemicals Generic Drug Formulations 1998 ......15 g Cyclamate sodium (Merck) ............... u.....................> 15 min Friability ......204 N Disintegration (water) ....................< 0......biplanar Hardness.................. Tablet properties Weight ............. mix and press with high compression force..9 Tablet formulations (Lab Scale) Vitamin A + Vitamin E Chewable Tablets (30.....602 mg Diameter ............. 3................................................ crystalline [10] ...8 mm sieve...425 g Orange flavour.......15 g 2........70 g SD 50 (BASF) Sorbitol..............................000 i......... Manufacturing (Direct compression) Pass all components through a 0........... u.....000 i.....66 g 500........................12 mm Form ............. + 35 mg) 1...................................................../g (BASF) Vitamin E acetate dry powder...9 g Polyethylene glycol 6000..............................................................2.....................

../g .... 2 Vitamin A palmitate 1....71....... II...7 Mio.5 g 2........0 g DL-alpha-Tocopherol (BASF) ................5 g 1......u.... 1 No....21... yellow........5 g 5. No...1.............8 Liquid Formulations (Lab scale) Vitamin A + Vitamin E Drops (25..................0 g Cremophor RH 40 [1] ..... with stirring. 72....q......... i..........7 Mio i....... Properties of the solutions Clear....5........0 g Preservative ... u...0 g 20..0 g – q...... u............... Manufacturing Mix the vitamins with Cremophor RH 40 (and DL-alpha-tocopherol) at 60 °C and then add solution II (at 37 °C) slowly...../g (BASF) Vitamin E acetate (BASF) ....... + 50 mg/ml) 1. Formulations I.. BASF Fine Chemicals Generic Drug Formulations 1998 .... Water.....s.................5 g 1. viscous liquids.5...................000 i....1..s. 3....

Vitamin A content [%] 4. Chemical stability of vitamin A in Formulation No. 2 100 90 23 °C 80 70 40 °C 0 3 BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 9 12 .

....15.. Vitamin A palmitate......15..5.....8 Liquid Formulations (Lab scale) Vitamin A + Vitamin E Drops (5...........33 g 1........ad 100 ml 2......u... + 50 mg/ml) 1......0........... BASF Fine Chemicals Generic Drug Formulations 1998 ..7 Mio i.... II.................. 3................ stir well and add slowly the mixture II............00 g Water.../g (BASF) Vitamin E acetate (BASF) ....... Manufacturing Heat mixture I to about 65 °C...... Formulation I... Properties of the solution Colour: yellow Clarity: clear (turbity units: 25 FTU) 4...... The addition of butylhydroxytoluene as antioxidant would be recommendable..6...00 g Ethanol 96 % ..............000 i................ Remarks It must be tested if the ethanol concentration has a sufficient preservative efficiency........u.........00 g Cremophor RH 40 [1] ..

........... II..........0 g Preservative (e......30.10......0 g 2..... 3.....57.......0...3 g 2..5 g Butylhydroxytoluene .g.s...2 g Solutol HS 15 [1] .................000 i.. stir well and add slowly the warm solution II. Properties of the solution Clarity: pH: Colour: Viscosity: clear to slightly opalescent 6....8 Liquid Formulations (Lab scale) Vitamin A + Vitamin E Injectable Solution for Sheeps (250..... Vitamin A propionate..... After the ampoules have been heat-sterilized........ Sterilization can also be performed by membrane filtration under pressure............q............... they should be shaken for a short time....2........ benzyl alcohol) . Formulation I..... while they are still hot........... Water for injectables ......... to eliminate any separation of the phases that may have occured..........u...../g (BASF) Vitamin E acetate (BASF) .3 yellow 45 mPa · s BASF Fine Chemicals Generic Drug Formulations 1998 .5 Mio i..........u. Manufacturing Heat mixture I to 70 °C.....5.. + 25 mg/ml) 1.

.................146 of Kollidon 30 Kollidon CL [1] ..300 mg Diameter ............< 0................................. u....... Manufacturing (Direct compression) Mix all components....................... Formulation Vitamin A acetate dry powder ............................... Tablet properties Weight .... 3..../g (BASF) Vitamin E acetate dry powder........................................................17 g g g g 2. granulated with 10 % ..........................................9 Tablet formulations (Lab Scale) Vitamin A + Vitamin E Tablets (33.............8 mm sieve and press with high compression force......38 N Disintegration..000 i........69 500....000 i....... + 70 mg) 1.......... pass through a 0.biplanar Hardness.....2.................12 mm Form ....................14 min Friability .....1% BASF Fine Chemicals Generic Drug Formulations 1998 .........................................................70 SD 50 (BASF) Mannitol........ u........

..........750 mg Diameter .................... u............................000 i.....................2... Tablet properties Weight ...... u........< 0................12 mm Form ...........25 Magnesium stearate (Merck) ......................... Manufacturing (Direct compression) Mix all components.......................111 N Disintegration .............................................................. pass through a 0../g (BASF) Mannitol...8 mm sieve and press with medium compression force..9 Tablet formulations (Lab Scale) Vitamin A Chewable Tablets (100.... 3..........5 Aerosil 200 [4] ....... Formulation Vitamin A acetate dry powder.......................1% BASF Fine Chemicals Generic Drug Formulations 1998 .............................biplanar Hardness ...........350 325...............................................350 Kollidon VA 64 [1] ..000 i...........................24 min Friability .....) 1..............................3 g g g g g 2.......................................

..................... Vitamin A palmitate 1... Properties of the solution Clear.... stir well and add very slowly the warm solution II (65 °C)................7 Mio i.. yellow liquid.............q.....ad 100 ml 2. BASF Fine Chemicals Generic Drug Formulations 1998 .. u. miscible with water..21.0 g Preservative . Water.s..... Physical stability (20–25 °C) No change of appearance after 3 months......... Manufacturing Heat the mixture I to about 65 °C.... II......5 g Butylhydroxytoluene ............ Formulation I................./ml) 1. 3.000 i... 4...8 Liquid Formulations (Lab scale) Vitamin A Concentrate........5.... Water-miscible (100........../g (BASF) .....0......6.....u........2 g Cremophor RH 40 [1].......

............– Butylhydoxytoluene (BHT) .../g (BASF). i....... u...8 Liquid Formulations (Lab scale) Vitamin A Drops (50.... 2 3.. II.... stir very well and add slowly the hot water (65 °C)... Physical stability (20–25 °C..7 Mio......0 5.... Properties of the solutions Yellow clear or slightly opalescent solutions of low viscosity.. protected from light) No change of clarity and colour after 1 year..... 3...............0 g Lutrol E 400 [1] .1 g Water ..........9 g g g g g 2. 1 I.. BASF Fine Chemicals Generic Drug Formulations 1998 ......... Vitamin A palmitate 1................3...............000 i................. Formulations No.../ml) 1........ Manufacturing Heat the mixture I to about 65 °C.......0............0 10.1 81. 4...85...9 g No.........0 0..5.11............0 g Cremophor RH 40 [1]. u...

Chemical stability (20–25 °C.Vitamin A [%] 5. protected from light) 100 Formulation 2 90 Formulation 1 80 70 0 3 BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 9 12 .

........ II.5...... stir well and add slowly the warm solution II.0 g Cremophor EL (or Cremophor RH 40) [1] .......... BASF Fine Chemicals Generic Drug Formulations 1998 ..... Properties of the solution Appearance: Clear........... Manufacturing Heat mixture I to about 60 °C................ 3./ml) 1...................20.....ad 100 ml 2..5.....22.. Vitamin A propionate ..........917 g/ml Viscosity (25 °C): 12 mPa · s 4... After the ampoules have been heat-sterilized.....0 g Benzylalcohol ... they should be shaken for a short time.. Formulation I.........0 g Water for injectables . Remark In Germany Cremophor EL must be declared on the package of injectables.....8 Liquid Formulations (Lab scale) Vitamin A Ethanolic Veterinary Injectable Solution (500. yellow Density (25 °C): 0..........5. to eliminate any separation of the phases that may have occurred........u. while they are still hot.......000 i..0 g Ethanol 96 % ........ Sterilization can also be performed by membrane filtration under pressure.

..40 Lutrol E 1500 [1] .......7 Formulations of semi-solid drugs (Lab scale) Vitamin A Suppositories (150.......80 Lutrol E 4000 [1].........................Homogeneously yellow Drop point:........... Properties of the suppositories Weight: ..........................................000 i...................................22 min (emulsion) BASF Fine Chemicals Generic Drug Formulations 1998 ....50 g g g g g 2.....54 °C Disintegration in water: .... 3..u........1 Cremophor RH 40 [1] ...7 Mio i. Fill into moulds of suppositories to obtain the weight of 2 g........u............... Manufacturing Dissolve butylhydroxytoluene in the warm vitamin A..............6.............9 Butylhydroxytoluene .) 1..0 g Colour: .................................../g (BASF)....... add Cremophor and mix with the molten Lutrol E grades...........2..................................... Formulation Vitamin A palmitate 1.....

.............) 1............100 Kollidon VA 64 [1] .000 i....... u........................ mix and press with low compression force..........1 g g g g g 2.... Manufacturing (Direct compression) Pass all components through a 0........10 Kollidon CL [1] ......................................110 500...231 mg Diameter ..64 N Disintegration ........... Tablet properties Weight ........................9 Tablet formulations (Lab Scale) Vitamin A Tablet Cores (50..................< 0......................................................8 mm sieve...............5 Aerosil 200 [4] ........... u.................000 i.......................... 3..........1% BASF Fine Chemicals Generic Drug Formulations 1998 ................... Formulation Vitamin A acetate dry powder .....2.........................................9 mm Form ......................................................................./g (BASF) Avicel PH 102 [5] .........biconvex Hardness...........2 min Friability ......................

......... sieve and press with high compression force using a vibrating hopper..biplanar Hardness..... .....0 granulated with 3 % of Kollidon 30 [1] Polyethylene glycol.........000 i............................................ dissolved in isopropanol or water and pass through a 0........ u............. DI-TAB [9].. 3.......6 g g g g g 2..................4 Aerosil 200 [4] .........55........572...................................0..680 mg Diameter ..40 N Disintegration ....................28.... Formulation Vitamin A acetate dry powder................. Tablet properties Weight ......2.................................19./g (BASF) Dicalcium phosphate.................000 i.4 % BASF Fine Chemicals Generic Drug Formulations 1998 .........................0 Kollidon CL [1] ...........2 min Friability...9 Tablet formulations (Lab Scale) Vitamin A Tablets (25...........) 1.....12 mm Form ............... Mix the obtained dried granules with the other components.......5...5 mm screen................... u.......... powder [6] ............................. Manufacturing Granulate the dicalcium phosphate with Kollidon 30..........0 500...............

... 1 No.... 3 Vitamin A acetate dry powder....306 mg Diameter.... Tablet properties No......................– 120 g 110 g 120 g 10 g – – 1g 1g – 154 g 10 g 4g – 1g 2..........000 i.. 2 No.. 1 No.. u..2..................................1 g Aerosil 200 [4] ......biplanar Hardness ..............................................................1% 277 mg 8 mm biplanar 119 N < 1 min < 0...189 g Avicel PH 101 [5] ......... u. Manufacturing (Direct compression) Mix all components..51 N Disintegration .... Formulation No...8 mm sieve and press with low compression force................1% BASF Fine Chemicals Generic Drug Formulations 1998 ..) 1.................................... 3..– Kollidon VA 64 [1] .............– Kollidon CL [1] . 3 Weight .......3 min Friability .......1% 250 mg 8 mm biplanar 106 N 7 min 0........110 g 500.....................................9 Tablet formulations (Lab Scale) Vitamin A Tablets (50.....< 0./g (BASF) Ludipress[1] ......– Magnesium stearate (Merck) .....................8 mm Form ..........000 i.............. 2 No.... pass through a 0......................

........2 g Cyanocobalamin dry powder 0...................................... Kollidon VA 64 [1] ...600 g Sodium bicarbonate (Merck).................. Fill 2............1 g of the granules in sachets......10 g Potassium L-aspartate ................... pass through a 0............. dry well and mix with III.. BASF Fine Chemicals Generic Drug Formulations 1998 ........... DL-Carnitine hydrochloride............ Administration 2.......4 Formulation of granules...........10 g II................ granulate mixture I + II with the liquid III...... anhydrous ....... dry syrups and Iyophylisates (Lab scale) Vitamin B Complex + Amino Acids + Magnesium Effervescent Granules (Sugar-free) (1 RDA of Vitamins + 500 mg carnitine + 20 mg glutamine) 1.............1 g disperse homogeneously in 100 ml of water in about 60 seconds.... Isdopropanol .....................500 g Flavours ........ s.... Formulation I............. 3.......... Properties of the granules Colour: Flowability: Dispersibility: Yellow granules Very good 2..........350 g Citric acid...20 g Inositol ............4...............2 g Pyridoxine hydrochloride (BASF)......1% (BASF)....8 mm sieve...................................500 g Magnesium L-aspartate ...............1 g of the granules correspond to about 1 RDA of the vitamins and 500 g of carnitin and 20 mg of glutamin..50 g III..... add the mixture II.........q.. Thiamin hydrochloride (BASF) ...............................80 g 2....5 g L-Glutamine .............. Manufacturing Mix the components I....... 4..

20.......2........50...............50.................14.......... Formulation I.............................0 g Biotin.................. Manufacturing (Wet granulation) Granulate mixture I with solution II..0.0 g Inositol ......0 g Nicotinamide (Degussa)... 3...................95................2........................... mix with III and press with low compression force.5 g (BASF) Carnitine hydrochloride ................... Kollidon 30 [1] . powder [6] ....................................708 mg Diameter ..........1% BASF Fine Chemicals Generic Drug Formulations 1998 ......... Kollidon CL [1]........................... gelatin coated 1%..........8 mm sieve...........0 g Lactose monohydrate [8]..............9 Tablet formulations (Lab Scale) Vitamin B Complex + Carnitine Tablet Cores 1....0 g II.....................15............ pass through a 0...1 – 2 min Friability ......................7 g Isopropanol .....100...0 g Riboflavin (BASF) ..................0....2 g Cyanocobalamin.....................0 g Polyethylene glycol 6000............................13 mm Form ................ Thiamine mononitrate (BASF) ....0.biconvex Hardness..................122............................0 g Adenosine phosphate ........................................................0 g III...........................0 g 2.........26...100........0 g Folic acid (Knoll) ...70.................88 N Disintegration................ Tablet properties Weight .............................................................. dry..............................0 g Calcium D-pantothenate (BASF) .....2..............

sediment volume: .........60 mg Manganese phosphate.... Evening primrose oil (see Remark) .........................................0 g Sucrose ...0 g III.. Formulation I.................. 3..........0......................25.3 mg Riboflavin (BASF) ......................41.....20 mg IV. Add the components III to the well stirred solubilisate I/II................3.............easy BASF Fine Chemicals Generic Drug Formulations 1998 ....10 µg Nicotinamide ............. Kollidon 90 F [1] ..1...............0 g Saccharin sodium ............................5...........................Viscous yellow suspension (syrup) pH:............................0 ml Cremophor RH 40 [1]........................................................ Properties Appearance: ................85 % after 1 week Redispersibility:................................16............3 Viscosity (25 °C): ..000 mPa · s Rel.......50 mg Kollidon CL-M [1] .......... Ferric citrate .....5.5............................................2 g Cyclamate sodium.......................0 g Citric acid ......8 Liquid Formulations (Lab scale) Vitamin B Complex + Minerals + Linoleic/Linolenic Acid Syrup 1..........2...............000 –17..............................................................0 g II....... crystalline ..... Water............... Finally add Kollidon 90 F to the obtained suspension portionwise with stirring.20......5 g 2..................................300 µg Thiamine hydrochloride (BASF) ......4 mg Cyanocobalamin.. Manufacturing Mix the primrose oil with Cremophor RH 40 heat to 60 °C and add slowly the warm water II.............................0......................5 g Vanilla-flavour (Gunther) ...................

Prima Rosa. Remark 5 ml of Evening Primrose oil (Epopure‚. South Africa) contain 3.4.5 g linoleic acid + 0.45 g gamma linolenic acid BASF Fine Chemicals Generic Drug Formulations 1998 .

.....164 g Sodium bicarbonate .............................300 g Sucrose..................0..........................................5 g (BASF)........................1%....150 N Disintegration ...................................550 g Riboflavin (BASF).......2....................50 g II..............5 g Nicotinamide ...........s........350 g Kollidon 30 [1] .......biplanar Hardness .................................................................... 3......................50 g 2............. Thiamine mononitrate (BASF) ....25 g Pyridoxine hydrochloride (BASF)........................................................... powder [6].................... dry at 60 °C with vacuum......... crystalline ..q... mix with III and press with medium to high compression force.................... Polyethylene glycol 6000.2...2 g Cyanocobalamin gelatin coated 0...........400 g Tartaric acid.....................400 g Sucrose.............. powder .............................................................10 g Isopropanol ................................................ Tablet properties Weight ......................12 g Calcium carbonate ......... Manufacturing (Wet granulation) Granulate mixture I with solution II.....................................7 g Riboflavin (BASF).......20 mm Form ...........75 g Calcium glycerophosphate ..................... Ascorbic acid.... Kollidon 30 [1] ....................... powder (BASF) .2 min Friability.......................... powder ............................................20 g Calcium D-pantothenate (BASF) ................................ Formulation I..................................... III..........................500 mg Diameter ..40 g Kollidon CL [1] .................................9 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C + Calcium Effervescent Tablets 1.........

............................... Kollidon 30 [1] ...................................................................... Tablet properties Weight ..........biplanar Hardness ...........20 mm Form ................................................................................750 mg Diameter ..................................300 g Kollidon 30 [1] .................................................9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C + Ferrous Sulfate Tablets 1.9 g 2.9 % BASF Fine Chemicals Generic Drug Formulations 1998 ............................... powder [6]...............8 mm sieve.......120 N Disintegration ......2............................. Ferrous sulfate (1H20)............................................................0.... pass through a 0...................s. 3.......................................................................1..................................82 g Nicotinamide .... powder (BASF) ..................45 g Riboflavin (BASF) ......50 g Aerosil 200 [4] .......... mix with III and press with high compression force (25 – 30 kN).........q........6 g 2-Propanol .....69 g Ascorbic acid....470 g Ludipress [1] ...........10 g Pyridoxine hydrochloride (BASF). Thiamine mononitrate (BASF) . Manufacturing (Wet granulation) Granulate the mixture I with solution II..............690 g Polyethylene glycol 6000.......................6 min Friability...... III............. Formulation I...15 g II........

....750 g Kollidon 30 [1] ................. Thiamine mononitrate (BASF) ...................................................... crystalline .............. 3..................... Formulation I..............................1% ............................ powder .....0.................... Ascorbic acid...................................................................s....................4 g Pyridoxine hydrochloride (BASF) ................10 g Saccharin sodium...... crystalline (BASF) .....17 g Tartaric acid.................................................................10 g Nicotinamide .................2.......biplanar Hardness ..10 g Orange flavour............................20 mm Form ...................3 g Cyanocobalamin gelatin coated 0................................66 g Calcium D-pantothenate (BASF) ...........................33 g Riboflavin (BASF)..........................2 g Cyclamate sodium... powder [6]................5 g Polyethylene glycol 6000........141 N Disintegration .... Isopropanol .......8 mm sieve.............q...............9 % BASF Fine Chemicals Generic Drug Formulations 1998 ....... mix with II and press with high compression force at maximum 30 % of relative atmospheric humidity............... III......2 min Friability.......................... Manufacturing (Wet granulation) Granulate mixture I with the solvent II....... dry...350 g Sodium bicarbonate .... Tablet properties Weight ................9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C Effervescent Tablets 1...........................................315 mg Diameter .............2................................500 g Riboflavin..............30 g II.................................50 g 2......... pass through a 0............450 g Sucrose......

...........1. II............1% (BASF) Ascorbic acid..2 g Riboflavin phosphate sodium ............. (or 10 g in 100 ml flaks as dry syrup)...... 3..1............ Formulation I...........4 Formulation of granules... Fill 1 g of the granules in sachets................ Manufacturing Mix the components I..... powder (BASF) ..0 g Pyridoxine hydrochloride (BASF).................. gelatin ...................17.... granulate with soluiton II.......8 mm sieve.......9 g Nicotinamide (Degussa) . Properties of the granules Yellow homogeneous granules dispersible in cold water... 4.0 g Sucrose .0 g Kollidon 30 [1] .......4... dry and pass through a 0......5 g Cyanocobalamin.241........... BASF Fine Chemicals Generic Drug Formulations 1998 ................1.60 ml 2...... Thiamine hydrochloride (BASF)......0 g coated 0..............0 g Ethanol ..... Administration About 1 g of the granules (= 1 sachet) correspond to two daily vitamin B and vitamin C requirements of adults.............15............ dry syrups and Iyophylisates (Lab scale) Vitamin B Complex + Vitamin C Instant Granules (2 RDA of Vitamins) 1.....................5.50..........

BASF Fine Chemicals Generic Drug Formulations 1998 .5. Remark Due to the high loss of riboflavin phosphate sodium it should be substituted by riboflavin. Chemical stability of the granules (20–25 °C) Vitamin After production 4 Months 6 Months B1 B2 B3 B6 B 12 C 100 % 100 % 100 % 100 % 100 % 100 % 93 % 80 % 98 % 97 % 100 % 97 % 100 % 93 % 100 % 100 % 100 % 100 % 6.

...200 mg Kollidon 25 [1] .................60 mg Riboflavin phosphate sodium...................................................................8 Liquid Formulations (Lab scale) Vitamin B Complex + Vitamin C Syrup................... Manufacturing Mix solution I with sugar syrup II.... II............................ 64 g + 36 g) Total amount ............... Use nitrogen as an inert gas in the final packaging.. Thiamine hydrochloride (BASF) .............120 mg Pyridoxine hydrochloride (BASF) ...............................5 g Sugar syrup DAB . BASF Fine Chemicals Generic Drug Formulations 1998 ...................................................2-Propylenglycol Pharma [1].........25 mg EDTA sodium ..50 mg Sorbic acid..55 mg Ascorbic acid.....9 g 1.........5............................................10 g Water ............................10 g Glycerol ........... crystalline (BASF)..55 mg Nicotinamide .. Formulation I................ Adjust the clear solution to about pH 4.................................250 mg Dexpanthenol (BASF) ...............5 mg Propyl gallate ..........2.............................5 g Sorbitol................................................................................. I (2 – 3 RDA/10 g) 1..100 g 2.................. crystalline [10] .....900 mg Orange flavour ..60 g (sucrose + water.....................

Vitamin B1 B2 Nicotinamide Dexpanthenol B6 C 0 Months 6 Months 9 Months 12 Months 100 % 100 % 100 % 100 % 100 % 100 % 95 % 100 % 92 % 95 % 100 % 94 % 87 % 90 % 96 % 88 % 100 % 90 % 82 % 92 % 92 % 90 % 88 % not determined BASF Fine Chemicals Generic Drug Formulations 1998 . dark) The following vitamin contents were determined by HPLC.3. Chemical stability (20–25 °C.

........... Properties of the solution Yellow clear taste full solution having a density of 1........216 g 2....................................... Parabene .........................8 Liquid Formulations (Lab scale) Vitamin B Complex + Vitamin C Syrup.. II 1. Use nitrogen as inert gas during packaging...5............. cool and mix with solution I/II...............50 mg EDTA sodium..................... Prepare solution III by heating..............250 mg Sorbitol....70 g Total amount ......... 3.....10 mg II.... Formulation I.................400 mg Orange aroma ..................100 g Water.............27 mg Nicotinamide ...................... crystalline [10] ........................30 g + water (2 + 1) III...........15 g Sucrose........2 – 4.. crystalline.............23 g/ml (25 °C).....27 mg Riboflavin phosphate sodium ... Manufacturing Dissolve the components I in mixture II.....27 mg Ascorbic acid...55 mg Pyridoxine hydrochloride (BASF).. Propylene glycol Pharma [1] ............................................................. crystalline (BASF)............. BASF Fine Chemicals Generic Drug Formulations 1998 ............. Thiamine hydrochloride (BASF) ......................... Adjust to pH 4.5................125 mg Dexpanthenol (BASF) ...............

4. Chemical stability (20–25 °C. Vitamin B1 B2 Nicotinamide Dexpanthenol B6 C 0 Months 6 Months 100 % 100 % 100 % 100 % 100 % 100 % 85 % 91% 100 % 88 % 100 % 89 % BASF Fine Chemicals Generic Drug Formulations 1998 9 Months 12 Months 85 % 91% 100 % 86 % 96 % – – 87 % 100 % 86 % 96 % 88 % . dark) The following vitamin contents were determined by HPLC.

4 g Kollidon VA 64 [1] .....0 g Nicotinamide........... 1 No......5 g Choline bitartrate ........................................... Manufacturing (Direct compression) Weigh all ingredients in...400 mg Diameter .......8 mm-sieve and mix.0...1% 411 mg 12 mm biplanar 69 N 5 min 0.............................172.............................0 g Thiamine hydrochloride (BASF) ..............20...................... Formulations No..............0 g – – 8............................. Press the mixture with medium/low compression force.........0 g Magnesium stearate [2] ..5.......................0 g 220.....................................95 N Disintegration ...........................5.9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C Tablets 1......................0...........0 g – 25...0 g – – 100...................– Biotin (Merck) ......... 2 Weight ....0 g Pyridoxine hydrochloride (BASF) .......................................................... Tablet properties No.......– Ribolfavin (BASF)..... ......... 2 Thiamine mononitrate (BASF) .....3 – 4 min Friability.......0.........................................0 g 5.........10........ 3...................................2.................0 g Folic acid ...................0 g 2............ pass through a 0....0 g – 10.............. 1 No...........................– – 15...10 mm Form ................................0 g Stearic acid [7] ...............2...............0 g 2..........– Niacin .0 g crystalline/powder (BASF) Ludipress [1] ................biplanar Hardness ..............................30................................3 % BASF Fine Chemicals Generic Drug Formulations 1998 .........150....................5..................................................1 g Calcium D-pantothenate (BASF) ............0 g Ascorbic acid.....................................................

BASF Fine Chemicals Generic Drug Formulations 1998 . Remark For stability reasons it would be better to substitute thiamine hydrochloride by thiamine mononitrate in formulation No. 2.4.

................ Vitamin B1 B2 Nicotinamide B6 B 12 9 Months 12 Months 8% 6% 0% 9% 13 % 11% 10 % 0% 9% not tested BASF Fine Chemicals Generic Drug Formulations 1998 ...... filter through a 0..86..2 µm membrane and fill the clear yellow solution in ampoules of 2 ml under nitrogen............... 3.. The pH-value is about 4..... Thiamine hydrochloride (BASF) ............4.................0 ml Propylene glycol Pharma [1] .......about 200 ml 2....... disodium salt...2..0 ml Water for injectables ................ II.......72............. Stability (20-25 °C....270 mg Sodium hydroxide solution 1 molar .........................................20..100 mg Riboflavin phosphate sodium........400 mg Pyridoxine hydrochloride (BASF) . Formulation I..........50 mg Kollidon 17 PF [1] .. Manufacturing Dissolve the mixture I in the buffer solution II....................660 mg Nicotinamide ...............21.6 ml Hydrochloric acid 0.....................160 mg Citric acid.20 mg Propyl gallate ...........5...............8 Liquid Formulations (Lab scale) Vitamin B Complex Injectable Solution 1...............................................880 µg EDTA....440 mg Cyanocobalamin .........1...........10 g Parabenes . dark) The following vitamin contents were determined by HPLC............1 molar ........................... keep it during 5 min under nitrogen bubbles.........................................4 ml Total amount ...

........0 mg Vanilline......................120..... propylene glycol and water.............0 mg EDTA sodium ............250...........0 mg Pyridoxine hydrochloride (BASF) .........................0 g 2.............2...........200.... Formulation Thiamine hydrochloride (BASF) ..5 g Kollidon 25 [1] ......0 mg Sucrose .........10...............9........0 mg Nicotinamide ...31.........225..................0 mg Dexpanthenol (BASF) .............8 Liquid Formulations (Lab scale) Vitamin B Complex Syrup 1................ Stability (room temperature...5....0 mg Sorbic acid ..0 mg Riboflavin 5-phosphate sodium ... HPLC) Vitamin Content after 1 year B1 B2 B6 Nicotinamide Dexpanthenol BASF Fine Chemicals Generic Drug Formulations 1998 80 % 75 % 97 % 97 % 92 % ....5.........55....5 g Glycerol ............46.0 g Water..................60................................ Manufacturing Dissolve the sucrose in the heat mixture of glycerol......................................................55........................................................................0 g Propylene glycol Pharma [1] . 3... cool to room temperature and dissolve the other components to obtain a clear solution...............

............................16 g Avicel PH 101 [5] ...................................... 2 Weight .........9 Tablet formulations (Lab Scale) Vitamin B Complex Tablets.................................. Manufacturing (Direct compression) Pass all component through a 0...40 g Pyridoxine hydrochloride (BASF)..... 1 No............. 1 No......................................... 3....4 % 504 mg 12 mm biplanar 68 N < 1 min 0.............................0.....8 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........................2....................1 % (BASF) ......3 g — 25 g 25 g 80 g 40 g 16 g 16 g 282 g 16 g 3g 2.. I 1..73N Disintegration............................................... 2 Thiamine mononitrate (BASF) ........................................................... Formulations No....................... mix and press with medium to high compression force.......................12 mm Form ......................16 g Aerosil 200 [4]..................................................................... Tablet properties No.< 1 min Friability ........282 g Kollidon 30 [1] ................................................................biplanar Hardness ..........................513 mg Diameter .....25 g Nicotinamide ................16 g Cyanocobalamin gelatin coated 0...........8 mm sieve.............80 g Calcium D-pantothenate (BASF)...— Riboflavin (BASF).......25 g Thiamine hydrochloride (BASF) ...

4. Chemical stability of vitamin B1 (40°C. BASF Fine Chemicals Generic Drug Formulations 1998 . 1 Formulation No. closed) 0 Month Formulation No. 2 100 % 100 % 6 Months 12 Months 83 % 32 % 72 % 11% Result: Thiamine hydrochloride is not suitable in this formulations.

............. 3...................... Formulation Thiamine mononitrate (BASF) ..................................................2...........0 g Magnesium stearate [1].5........ Tablet properties Weight ....05 g Cyclamate sodium........biplanar Hardness ...............6 min Friability.......76 N Disintegration .......................0 g 2......2............2.......................... Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application.......................0..............................4..........280..........0 g Saccharin sodium........2...............7 g Cyanocobalamin gelatin coated 0.......8 mm Form ..................3 g Riboflavin (BASF).4 g (BASF) Ludipress [1] ............. II 1............................................2.......................3 g Calcium D-pantothenate (BASF)...........................9 Tablet formulations (Lab Scale) Vitamin B Complex Tablets...... mix and press with low compression force.2...................................0.6 g Nicotinamide .........2.......................................1% ..........2 g Pyridoxine hydrochloride (BASF)................................... Manufacturing (Direct compression) Pass all component through a 0...... BASF Fine Chemicals Generic Drug Formulations 1998 ....................314 mg Diameter .......................1% 4.....................8 mm sieve................14....0 g Flavour (Firmenich).....

q.............101 N Disintegration ..................s............... Formulation I..................... mix with III and press with low compression force.................................2..................................... III.......2 min Friability .........16 mm Form ............................. dry............................................. Thiamine hydrochloride (BASF)......................................... Polyethylene glycol 6000........0............................ 3..........................................15 g Ethanol 96 % .......................30 g Kollidon VA 64 [1] ...................................5 % BASF Fine Chemicals Generic Drug Formulations 1998 .biplanar Hardness..........100 g Corn starch [3] ..... Manufacturing (Wet granulation) Granulate mixture I with solution II..........................................................35 g 2............9 Tablet formulations (Lab Scale) Vitamin B1 + Caffeine Tablets (500 mg + 100 mg) 1.............................20 g II.......... Kollidon VA 64 [1] . powder [6] ....698 mg Diameter ............. Tablet properties Weight .......500 g Caffeine (Knoll) ........................... sieve.................

............... II.. 3...0 g Pyridoxine hydrochloride (BASF)...960 ml 2........6 g Nicotinamide ... 4....... Chemical stability (20–25°C) Vitamin Content after 1 year (HPLC) B1 B2 B3 B6 93 % 90 % 100 % 97 % Vitamin B 12 was not stable in this formulation BASF Fine Chemicals Generic Drug Formulations 1998 ...2 g Sodium hydroxide solution......5.....6.0.... sodium ..... Flush 5 –10 min..........8 Liquid Formulations (Lab scale) Vitamin B1 + Vitamin B2 + Vitamin B3 + Vitamin B6 Injectable Solution (100 mg + 6 mg + 40 mg + 4 mg/2 ml) 1...4 g Parabene ....8 g Citric acid .800 ml Water for injectables ........1....................... 0..........22 µm membrane and fill into 2-ml ampoules under nitrogen.. 1 molar ...240 ml Hydrochloric acid.............44. with nitrogen..... Manufacturing Prepare solution II by heating and allow to cool before dissolving the components of I in it.......11....1 molar ......................... Formulation I........25... filter through a 0.............0 g Riboflavin-5’-phosphate............ Properties of the solution A clear yellow solution was obtained having a pH of a about 4.4......... Thiamine hydrochloride (BASF) ....................................

............8 mm sieve..............................277 g Magnesium stearate [2] .................................................... gelatin coated 1% (BASF) ............................................3 g 2........................9 Tablet formulations (Lab Scale) Vitamin B1 + Vitamin B6 + Vitamin B12 Tablets (100 mg + 10 mg + 100 µg) 1..2..........10 g Ludipress [1] ..................................100 g Pyridoxine hydrochloride (BASF)........................................................63 N Disintegration .......... 3................394 mg Diameter .................4 min Friability .......biplanar Hardness .....10 g Cyanocobalamin.............0....... Tablet properties Weight ..12 mm Form ................................ Formulation Thiamine hydrochloride (BASF) ...............3 % BASF Fine Chemicals Generic Drug Formulations 1998 .................. Manufacturing (Direct compression) Pass all components through a 0......................................... mix and press with low compression force.............

......8 mm sieve and press with low compression force........... powder [6] ..................................5 min Friability ........ pass through a 0........................................2.............2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................................102 N Disintegration ...........45 g Aerosil 200 [4]............9 Tablet formulations (Lab Scale) Vitamin B1 + Vitamin B6 + Vitamin B12 Tablets (100 mg + 200 mg + 100 µg) 1........................ 3.... Formulation Thiamine mononitrate (BASF) ...........5 g 2.....................12 mm Form .....................10 g Ludipress [1] .....200 g Cyanocobalamin gelatin coated 1% (BASF) ..................................................................................................biplanar Hardness..........0...................................250 g Polyethylene glycol 6000.........609 mg Diameter ....100 g Pyridoxine hydrochloride (BASF).. Tablet properties Weight ............................................ Manufacturing (Direct compression) Mix all components..............................

..12 mm Form ............250 g Pyridoxine hydrochloride (BASF)..........9 –10 min Friability ... Tablet properties Weight ..s....................................4 % BASF Fine Chemicals Generic Drug Formulations 1998 .............2............. pass through a 0............... Cyanocobalamin...........9 Tablet formulations (Lab Scale) Vitamin B1 + Vitamin B6 + Vitamin B12 Tablets (250 mg + 250 mg + 1 mg) 1........... Kollidon 30 [1].............................................25 g Isopropanol........... Manufacturing (Wet granulation) Granulate mixture I with solution II.................................730 mg Diameter .................................... mix with III and press with low compression force applying a vibrating hopper.2 g Talc [10] ..................... III... 3..............................................0...... dry.............................................8 mm sieve.............................biplanar Hardness ............. gelatin coated 1%..................25 g Magnesium stearate [2] .....................................75 g II..................................................95 N Disintegration .............................250 g Lactose monohydrate [8] ....... Formulation I....q..5 g 2........................ Thiamine mononitrate (BASF) .....100 g (BASF) Kollidon CL [1] .....................................................................

....... Formulation No............................293 g Magnesium stearate [2] .... Tablet properties No.........................................................357 mg Diameter ...................50 g Thiamine mononitrate (BASF) ........5 g Aerosil 200 [4]...........................................1% 347 mg 12 mm biplanar 108 N 7 min < 0.......... mix and press with medium compression force.........0..110 N Disintegration .............2 g No.. 2 Weight . 3.........................................................2 – 3 min Friability...............12 mm Form ..........– Ludipress [1] .......... Manufacturing (Direct compression) Pass all components through 0......................... 1 No....9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (50 mg)................. I 1................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...........................2........ 2 50 293 5 2 – g g g g 2............................................................................................biplanar Hardness ...5 mm sieve......................... 1 Thiamine hydrochloride (BASF) ....

.....................................5 mm sieve.....1% 4............................12 mm Form ..... Manufacturing (Direct compression) Pass all components through 0............................................... 3........ II 1.............. Tablet properties No................ 1 Formulation No..... closed) Formulation No..........150 N Disintegration .................2 min Friability.. 2 50 150 150 15 2 g g g g g 2..................1% 373 mg 12 mm biplanar 150 N < 1 min < 0........................... 1 No....................50 g Thiamine mononitrate (BASF) ..............344 mg Diameter ...................9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (50 mg).......................................... mix and press with high compression force......... Formulation No........– Lactose monohydrate [8] ..........150 g Kollidon CL [1] ................150 g Avicel PH 101 [5] ..................................................15 g Aerosil 200 [4]........2................. 2 0 Months 3 Months 100 % 100 % 98 % 100 % BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 12 Months 90 % 96 % 97 % 97 % .........0............................. 1 Thiamine hydrochloride (BASF) ...... Chemical stability of thiamine (40 °C................biplanar Hardness........2 g No..................................... 2 Weight ...

..... Formulations No......... DC 1...............biplanar Hardness ................302 mg Diameter ........2........... Tablet properties No....5 mm sieve.............. 1 No............................................................................114 N Disintegration .........................190 g Lactose monohydrate [8] ............... 2 Thiamine hydrochloride (BASF) ......................................................................................................2 g – 100 g – 100 g 100 g 9g 1g – 2........................................2 % 320 mg 8 mm biplanar 150 N < 1 min 0............ 1 No.– Kollidon CL [1] . mix and press with medium compression force... 2 Weight ..................– Aerosil 200 [4].....– Avicel PH 101 [5].....................................110 g Thiamine mononitrate (BASF) ........................0.....................– Ludipress [1] ............................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........................................3 g Magnesium stearate [2] .................2 min Friability .. 3...8 mm Form ..................9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (100 mg)................................................. Manufacturing (Direct compression) Pass all components through 0.....................................

..........................100 Lactose monohydrate [8] ...........7 min Friability ...............8 mm screen...............................2 Aerosil 200 [4].... WG 1.................10 Isopropanol..............................................1 g g g g g g g 2.8 mm Form ......................................9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (100 mg)...60 III...... Kollidon 30 [1] ...... Manufacturing (Wet granulation) Granulate mixture I with solution II.........................................................9 % BASF Fine Chemicals Generic Drug Formulations 1998 .................................10 Magnesium stearate [2] ........ Kollidon CL [1] ......................................................330 mg Diameter ........................0..............200 II............................2..................................................174 N Disintegration .. 3........... dry and sieve through a 0.........................biplanar Hardness .................................... Tablet properties Weight .............. Formulation I....... mix with III and press to tablets................ Thiamine hydrochloride (BASF) ...................................

.. Kollidon CL [1] ............................................ Manufacturing (Wet granulation) Granulate mixture I with solution II...... DI-TAB [9] .....70 N Disintegration .......10 Magnesium stearate [2] ....15 Isopropanol .7 % 4................. dry and sieve through a 0.................. Formulation I...........................................................................................................100 II....... Chemical stability (30°C.......................about 50 III................................430 mg Diameter .................9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (300 mg) 1................................................................... Thiamine mononitrate (BASF) .......................4 g g g g g g 2.8 mm screen...................2.................. 70% relative humidity) Vitamin B1 content 0 Month 3 Months 6 Months 298 mg 298 mg 295 mg = 99 % BASF Fine Chemicals Generic Drug Formulations 1998 ....................... Kollidon 30 [1] ........... 3... Tablet properties Weight ............. mix with III and press to tablets.................3 – 4 min Friability .12 mm Form .......0.................................................300 Dicalcium phosphate.biplanar Hardness ..

.........0 Sicovit yellow orange lake [1] ............. 3.............................. orange BASF Fine Chemicals Generic Drug Formulations 1998 ...............1%.....8 mm Form ...........9 Tablet formulations (Lab Scale) Vitamin B12 (Cyanocobalamin) Tablets................................50........1% Colour .............................biplanar Hardness .. Coloured (50 µg) 1..0 Magnesium stearate [2] ..............................................5 mm sieve and press with low compression force................................ Formulation I...209 mg Diameter .......... add to mixture I.2.....150..........................0 g g g g g 2............0 (BASF) Ludipress [1] . pass through a 0..........2.......homogeneous..........80 N Disintegration ........5 Sicovit quinoline yellow lake [1] ................................................ Tablet properties Weight .....10 min Friability ........... Manufacturing (Direct compression) Prepare the premix II......1.< 0......................................3......................................... Cyanocobalamin gelatin coated 0...... II.....................

.............................. Remarks These tablets could be commercialized in Europe as dietary food because all components are allowed for this application...............biplanar Hardness .............................9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (3 mg) 1..........2 Aerosil 200 [4]..........195 Magnesium stearate [2] .................................8 mm sieve......... BASF Fine Chemicals Generic Drug Formulations 1998 ................................................3 Ludipress [1] ..............................................8 mm Form ........................ Formulation Ribolfavin C (BASF) ................. Tablet properties Weight ................................1 g g g g 2......... Manufacturing (Direct compression) Pass all components through a 0. mix and press with very low compression force (4 kN)...... 3..............0............................................................97 N Disintegration ........................2................................ If the content uniformity does not meet the requirements it would be recommended to prepare a premix of the active ingredient with a small part of the Ludipress or with lactose monohydrate before mixing with the other components of the formulation.1% Content uniformity: meets the requirements of DAB 4....202 mg Diameter ..................3 – 4 min Friability................................

0 Lactose monohydrate [8] ....................5 Hydrogenated castor oil (Henkel)...2........1.......0 Corn starch [3] ......0 II......< 0........20............................................................. dry...... Aerosil 200 [4] .........................7 g g g g g g g g g 2................................ Riboflavin (BASF) .........................................................................82 N Disintegration................8 Talc [10] .................. mix with II and press with low compression force....... 3.....................................1 – 2 min Friability ........75..... Formulation I..........................9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (10 mg) 1..................134 mg Diameter .......25 III........... Manufacturing (Wet granulation) Granulate mixture I with solution II......................................................... Tablet properties Weight ............10.....15..........2...1% BASF Fine Chemicals Generic Drug Formulations 1998 ...............8 mm sieve......................5 Water ....................0 Avicel PH 101 [5] ......8 mm Form .....................biplanar Hardness ............ pass through a 0.........................................................0............................... Kollidon 30 [1]............................................

.........................biplanar Hardness.375 Kollidon VA 64 [1] ............................... 3...........................................................0................... Manufacturing (Direct compression) Pass all components through a 0..................................12 g g g g g 2. crystalline [10]................................10 min Friability .....9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (75 mg) 1....................493 mg Diameter ...........23 Magnesium stearate [2] .......12 mm Form ................................ Formulation Riboflavin (BASF).......................................................................................................................................................8 mm sieve.................4 Aerosil 200 [4] ...................................75 Sorbitol... Tablet properties Weight ......2........ mix and press with low compression force.100 N Disintegration .....5 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........................

..................384 mg Diameter ..................................................................................10 g g g g g 2.. Manufacturing (Direct compression) Pass all components through a 0........5 Aerosil 200 [4] ................. 3......................2......................100 Sorbitol.19 Magnesium stearate [2] .......... mix and press with medium compression force.................12 mm Form ..............250 Kollidon VA 64 [1] . crystalline [10].......................................... Tablet properties Weight ......................................................................................... Formulation Riboflavin ...............................9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (100 mg) 1................................................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............................................biplanar Hardness ........7 min Friability ......8 mm sieve......................0.............................53 N Disintegration .....

............................150 Magnesium stearate [2] .................66 N Disintegration ............8 mm sieve and press with low compression force............... Tablet properties Weight ................................... Manufacturing (Direct compression) Mix all components.................................................................................... Formulation Ribolfavin (BASF) ...... 3..0.......................9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (150 mg) 1...............4 Aerosil 200 [4]......................8 mm Form ........................................................................308 mg Diameter .... pass through a 0......2.........................................2 min Friability......biplanar Hardness .................1% BASF Fine Chemicals Generic Drug Formulations 1998 ..............2 g g g g 2.............................156 Ludipress [1] ..........................................................

..........................................3 g g g g g 2.....................................................3 Aerosil 200 [4]..............16 Magnesium stearate [2] ................................................0.........................................................biplanar Hardness .....8 mm sieve....... Formulation Nicotinamide (Degussa) .2 % BASF Fine Chemicals Generic Drug Formulations 1998 ............................................................................................320 Avicel PH 101 [5] .......9 Tablet formulations (Lab Scale) Vitamin B3 (Nicotinamide) Tablets (300 mg) 1.................2..........................................89 N Disintegration......................< 1 min Friability ............................12 mm Form ........160 Kollidon VA 64 [1] ............... 3........... mix and press with medium compression force.......................... Tablet properties Weight .............506 mg Diameter . Manufacturing (Direct compression) Pass all components through a 0...................

..................................q.......< 0..... mix and press with low compression force.........................s......................biplanar Hardness ........987 mg Diameter ................ Manufacturing (Direct compression) Pass all components through a 0...................................................... Formulation Calcium D-Pantothenate (BASF)................... crystalline [10] .3 % 4..... powder [6] ...............................2...8 mm sieve................ BASF Fine Chemicals Generic Drug Formulations 1998 ........................................... Tablet properties Weight .........150 g Avicel PH 101 [5] ................................................ 2................................................................9 Tablet formulations (Lab Scale) Vitamin B5 (Calcium D-Pantothenate) Chewable Tablets (600 mg) 1...............610 g Sorbitol.> 150 N Disintegration (water) ... 3....140 g Kollidon CL [1] ..........................30 g Polyethylene glycol 6000..........................12 mm Form ....................... Remark Perhaps the addition of Kollidon CL is not needed..19 min Friability .......50 g Flavours...........

............................................. 3...........2.................................................................196 N Disintegration ........................8 mm Form ............. Manufacturing (Direct compression) Mix all components................3 g g g g 2................................................................................................biplanar Hardness.6 min Friability ..1% BASF Fine Chemicals Generic Drug Formulations 1998 .......................10 Magnesium stearate [2] . pass through a 0. Tablet properties Weight ..................................................................< 0...........................................9 Tablet formulations (Lab Scale) Vitamin B5 (Calcium D-Pantothenate) Tablets (100 mg) 1.. Formulation Calcium D-Pantothenate (BASF)..................150 Kollidon CL [1] ....100 Ludipress [1] .............................8 mm sieve and press to tablets with medium compression force..............252 mg Diameter ...

...........8 mm sieve and press to tablets with medium compression force...2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................................................................... Tablet properties Weight ............................................100 N Disintegration..........................3 g g g g g g 2....................12 mm Form ....................biplanar Hardness.......................< 0..9 Tablet formulations (Lab Scale) Vitamin B5 (Calcium D-Pantothenate) Tablets (280 mg) 1..... Formulation Calcium D-Pantothenate (BASF) ...................285 Avicel PH 101 [5] ................50 Dibasic calcium phosphate DI-TAB [9] .........................11 min Friability ............................ pass through a 0....................................2....................... Manufacturing (Direct compression) Mix all components...........3 Magnesium stearate [2] ......150 Kollidon CL [1] .........................................518 mg Diameter ..............................................20 Stearic acid [7]................................. 3.....................

........................................... Formulations No........... crystalline [10] .........60 g Corn starch [3] ...............biplanar Hardness ...52 g Calcium arachinate [2] ...................................100 g Kollidon VA 64 [1] .....12 mm Form ....................................... 1 No........................25 g Talc [10] ........6 g Aerosil 200 [4]................................. 2 Calcium D-Pantothenate (BASF) ...................................2.................. 1 No.................................– 305 g – – 75 g 70 g – 15 g – – – 25 g 2. Tablet properties No...0.........12 g Kollidon CL [1] ............... Manufacturing (Direct compression) Mix all components.................................... 3....................8 % 488 mg 12 mm biplanar 135 N 5 min < 0...................................................................................11 min Friability .. 2 Weight ........................................ pass through a 0..................................................6 g Polyethylene glycol 6000.......9 Tablet formulations (Lab Scale) Vitamin B5 (Calcium D-Pantothenate) Tablets (300 mg) 1...300 g Lactose Monohydrate [8] .– Avicel PH 101 [5] .................8 mm sieve and press to tablets with medium/low compression force.................................62 N Disintegration...............1% BASF Fine Chemicals Generic Drug Formulations 1998 .............................604 mg Diameter ........................50 g Sorbitol............. powder [6] ......................................................

...........................................40 g Lactose monohydrate [8] ................................................................................................1% 340 mg 12 mm biplanar 81 N 2 min 0..150 g Kollidon VA 64 [1] ..........................9 Tablet formulations (Lab Scale) Vitamin B6 (Pyridoxine) Tablets (40 mg).........................1 g 40 g 150 g 150 g – – 1g 1g 2....................5 mm sieve...........2.... 1 No....................................15 g Kollidon CL [1] ...................... DC 1..... Manufacturing (Wet granulation) Pass all components through a 0........ 1 No......< 0................................ Chemical stability of Formulation No.....12 mm Form .................140 N Disintegration ..2 min Friability ........... Tablet properties No..........1 g Aerosil 200 [4].............................361 mg Diameter .... 2 Pyridoxine hydrochloride (BASF) ...................................... Formulations No...10 g Magnesium stearate [2] . 1 (40°C............................................................... closed) Vitamin B 6 0 Months 3 Months 6 Months 100 % 100 % 100 % BASF Fine Chemicals Generic Drug Formulations 1998 ............biplanar Hardness......... mix and press with high compression force... 2 Weight ....150 g Avicel PH 101 [5] ............................2 4............. 3..............

....................................................................3 min Friability............9 Tablet formulations (Lab Scale) Vitamin B6 (Pyridoxine) Tablets (40 mg)...................... WG 1..........biplanar Hardness ..............12 mm Form ....................2........... Formulation I..............0......................... Tablet properties Weight ......1% 4........ dry. Kollidon 30 [1] .................................................................................... closed) 0 Months 3 Months 6 Months 100 % 100 % 100 % Vitamin B 6 BASF Fine Chemicals Generic Drug Formulations 1998 . Manufacturing (Wet granulation) Granulate mixture I with solution II................... Magnesium stearate [2] ...1 g Aerosil 200 [4]. Chemical stability (40°C................80 g III.....15 g Water + Isopropanol (1+1) ......2 g 2........................ Pyridoxine hydrochloride (BASF) .................70 N Disintegration ...... pass through a 0........8 mm sieve........................... 3..300 g II................................................354 mg Diameter ..................................40 g Corn starch [3] .... mix with III and press with high compression force..................................................

mix and press with medium compression force.......... 2 Weight .........................................2 % 360 mg 12 mm biplanar 61 N < 1 min < 0.................3 g Magnesium stearate [2] .......... Formulations No.....................................363 mg Diameter ..................................9 Tablet formulations (Lab Scale) Vitamin B6 (Pyridoxine) Tablets (100 mg) 1............10 g Kollidon CL [1] ...............................100 g Tabletlose [8]....74 N Disintegration.......1 g 100 g – 150 g 83 g 10 g 3g 1g 1g 2....12 mm Form ..............................................................< 1 min Friability ...............................................0....... 2 Pyridoxine hydrochloride .............................. Manufacturing (Direct compression) Pass all components through a 0................ 1 No...............................................................................2............. 1 No..... 3................................– Kollidon VA 64 [1] .................200 g Lactose monohydrate [8] ...................1 g Aerosil 200 [4]...........................................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...........biplanar Hardness ............... Tablet properties No.....................– Avicel PH 101 [5]......................8 mm sieve...........

............ 3..53 N Disintegration ................................................................................12 g Magnesium stearate [2] ...100 g Kollidon VA 64 [1] .............................. Formulation Pyridoxine hydrochloride (BASF)............................................8 mm sieve..............biplanar Hardness ...............................250 g Avicel PH 101 [5] .......................2 – 3 min Friability ......361 mg Diameter ......5 g 2............................................... mix and press with high compression force........................ Manufacturing (Direct compression) Pass all components through a 0..........1% BASF Fine Chemicals Generic Drug Formulations 1998 ...< 0.................................2...... Tablet properties Weight .................................................12 mm Form ..................9 Tablet formulations (Lab Scale) Vitamin B6 (Pyridoxine) Tablets (250 mg) 1....................

..............300 g Lactose monohydrate D 20 [8] ...................0............440 mg Diameter .........................................biplanar Hardness .... 3.20 g Isopropanol + water (1+1) ....... Pyridoxine hydrochloride (BASF)..............................60 g III........................10 g Aerosil 200 [4]. Kollidon CL [1] ......8 min Friability................110 N Disintegration .................. BASF Fine Chemicals Generic Drug Formulations 1998 ......................................9 Tablet formulations (Lab Scale) Vitamin B6 (Pyridoxine) Tablets (300 mg) 1...... Press with medium compression force....... Tablet properties Weight .........................................2................................................. Manufacturing (Wet granulation) Granulate mixture I with solution II..... dry and sieve through a 0.................................................................12 mm Form ................8 mm screen.100 g II..... Kollidon 30 [1].................. closed) No loss of vitamin B6 after 3 and 6 months.................... Chemical stability (40 °C....................2 g 2.......................... Formulation I.....................................1% 4.....

2.9 Tablet formulations (Lab Scale)

Vitamin C + Calcium Carbonate
Effervescent Tablets
(500 mg + 300 mg)
1. Formulation
I.

Calcium carbonate .......................................315 g
Sodium bicarbonate .....................................450 g
Tartaric acid, powder ....................................600 g
Kollidon 30 [1]................................................35 g
II. Kollidon 30 [1] ................................................10 g
Isopropanol..................................................200 g
III. Sucrose crystalline .......................................400 g
IV. Ascorbic acid, crystalline (BASF) ...................550 g
Kollidon CL [1]..............................................120 g
Polyethylene glycol 6000, powder [6] ..............60 g

2. Manufacturing (Wet granulation)
Granulate mixture I with solution II, mix with III and dry. Add IV and press
with a high compression force at maximum 30 % of relative atmospheric
humidity.

3. Tablet properties
Weight ...................................................2,500 mg
Diameter ....................................................20 mm
Form ........................................................biplanar
Hardness.....................................................100 N
Disintegration ...............................................2 min
Friability ..........................................................2 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C + Vitamin E Lozenges
(100 mg + 50 mg)

1. Formulation
I.

Ascorbic acid, crystalline (BASF) ...................100 g
Vitamin E acetate dry powder SD 50 (BASF) ..100 g
Dextrose ......................................................400 g
Kollidon 90 F [1] ...............................................4 g
II. Isopropanol....................................................25 g
III. Polyethylene glycol 6000, powder [6] ................6 g

2. Manufacturing (Wet granulation)
Granulate mixture I with isopropanol, dry, pass through a 0.8 mm sieve,
mix with III and press with high compression force.

3. Tablet properties
Weight ......................................................600 mg
Diameter ....................................................12 mm
Form ........................................................biplanar
Hardness ......................................................61 N
Friability .....................................................< 0.1%

4. Stability of appearance
No change of the tablet colour during 3 months at 30 °C and 70 %
relative humidity.

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic acid) Chewable Tablets
(100 mg, 500 mg, 1,000 mg)

1. Formulation
Ascorbic acid, powder (BASF) .....................42.2 %
Microcristalline cellulose, .............................28.3 %
e.g. Avicel PH 101 [5]
Sucrose, powder ........................................13.0 %
Sucrose, crystalline.......................................8.0 %
Kollidon VA 64 [1] .........................................2.4 %
Cyclamate sodium ........................................2.4 %
Polyethylene glycol 6000, powder [6] .............2.0 %
Orange flavour + strawberry flavour (2+1).......1.2 %
Aerosil 200 [4] ..............................................0.2 %
Saccharin sodium .........................................0.1%

2. Manufacturing (Direct compression)
Mix all components, pass through a 0.8 mm sieve and press to tablets
with medium to high compression force.

3. Tablet properties
Vitamin C content / Tablet
100 mg
500 mg
1000 mg
Weight
Diameter
Form
Hardness
Disintegration (water)
Friability

250 mg
8 mm
biplanar
157 N
15 min
< 0.1%

1250 mg
15 mm
biplanar
> 100 N
> 15 min
0.8 %

2500 mg
20 mm
biplanar
> 150 N
14 min
0.6 %

4. Remark
This formulation also is mentioned in “Standardzulassungen für Fertigarzneimittel”, Deutscher Apothekerverlag, 1988.

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic Acid + Ascorbate)
Chewable Tablets
(500 mg)
1. Formulations
No. 1
Ascorbic acid, crystalline (BASF) ..................500 g
Sodium ascorbate, crystalline (BASF) ...................–
Sorbitol, crystalline [10] ..............................1,100 g
Sucrose, crystalline .............................................–
Sucrose, powder.................................................–
Dextrose ......................................................300 g
Polyethylene glycol 6000, powder [6].............100 g
Magnesium stearate [2]...................................10 g
Aerosil 200 [4] ................................................10 g
Saccharin sodium ...............................................–
Cyclamate sodium..........................................10 g
Orange flavour ...............................................30 g

No. 2
100
450
264
200
200

g
g
g
g
g

60 g
3g
4g
1g

20 g

2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with
medium to high compression force.

3. Tablet properties
No. 1

No. 2

Weight ...................................................2,080 mg
Diameter ....................................................20 mm
Form ........................................................biplanar
Hardness ..................................................> 150 N
Friability .......................................................0.7 %

1,295 mg
16 mm
biplanar
126 N
0.7 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic acid) Chewable Tablets
with Dextrose
(100 mg)
1. Formulations
No. 1

No. 2

Ascorbic acid, crystalline ..............................105 g
Ascorbic acid, EC coated 97.5 % (Merck)..............–
Dextrose ......................................................500 g
II. Kollidon 90 F [1] ...............................................4 g
Water and/or isopropanol.........................30 – 50 g
III. Polyethylene glycol 6000, powder [6] ................6 g


110 g
500 g
4g
30 – 50 g
6g

I.

2. Manufacturing (Wet granulation)
Granulate mixture I with solution II (in a fluidized bed), sieve, add III and
press with high compression force.

3. Tablet properties
No. 1

No. 2

Weight ......................................................620 mg
Diameter ....................................................12 mm
Form ........................................................biplanar
Hardness.....................................................150 N
Disintegration .............................................10 min
Friability .....................................................< 0.1%

620 mg
12 mm
biplanar
> 100 N
not tested
0.1%

BASF Fine Chemicals Generic Drug Formulations 1998

4. Chemical stability (40 °C, closed)
0 Months

3 Months

6 Months

100 %
100 %

100 %
92 %

100 %
93 %

Formulation No. 1
Formulation No. 2

5. Remarks
1. If no fluidized bed is available water should be avoided as granulation
solvent.
2. The use of coated ascorbic acid does not increase the stability.

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic Acid) Chewable Tablets
with Fructose
(120 mg)
1. Formulation
Ascorbic acid, powder (BASF) .......................120 g
Fructose ......................................................500 g
Ludipress [1] ................................................200 g
Avicel PH 101 [5] ..........................................100 g
Kollidon VA 64 [1] ...........................................15 g
Aerosil 200 [4]..................................................4 g
Polyethylene glycol 6000, powder [6] ..............35 g

2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with high
compression force.

3. Tablet properties
Weight ......................................................970 mg
Diameter ....................................................12 mm
Form ........................................................biplanar
Hardness.....................................................222 N
Disintegration (water) ....................................9 min
Friability ..........................................................0 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic acid) Chewable Tablets
with Sucrose
(500 mg)
1. Formulation
Ascorbic acid (BASF) ....................................500
Sucrose, crystalline ......................................850
Avicel PH 101 [5] ..........................................575
Kollidon VA 64 [1] ...........................................60
Magnesium stearate [2] ..................................15

g
g
g
g
g

2. Manufacturing (Direct compression)
Pass all components through a 0.8 mm sieve, mix and press with
medium compression force.

3. Tablet properties
Weight ...................................................2,000 mg
Diameter ....................................................20 mm
Form ........................................................biplanar
Hardness.....................................................130 N
Disintegration...........................................> 20 min
Friability .......................................................0.5 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic acid) Effervescent
Tablets
(100 mg and 1000 mg)
1. Formulation
No. 1
100 mg

No. 2
1000 mg

Ascorbic acid, powder (BASF) .......................112 g
Ascorbic acid, crystalline (BASF) ..........................–
Sorbitol, crystalline [10] .......................................–
Sorbitol Instant (Merck) .................................200 g
Citric acid, anhydrous .................................1000 g
Sodium bicarbonate .....................................587 g
Polyethylene glycol 6000, powder [6] ..............65 g
Lemon flavour ................................................10 g
Cyclamate sodium..........................................25 g
Saccharin sodium ............................................1 g


1000 g
800 g

150 g
660 g
80 g
q.s.
q.s.
q.s.

2. Manufacturing (Direct compression)
Dry the sodium bicarbonate during 1 hour at 100 °C, mix with the other
components, pass all through a 0.8 mm sieve and press with high
compression force at maximum 30 % of relative atmospheric humidity.

3. Tablet properties
No. 1
Weight ....................................................2050 mg
Diameter ....................................................20 mm
Form ........................................................biplanar
Hardness.....................................................150 N
Disintegration (water) ...............................2 – 3 min
Friability .....................................................< 0.1%

No. 2
2,690 mg
20 mm
biplanar
174 N
2 – 3 min
0.8 %

BASF Fine Chemicals Generic Drug Formulations 1998

2.9 Tablet formulations (Lab Scale)

Vitamin C (Ascorbic Acid) Effervescent
Tablets
(500 mg)
1. Formulation
I.

Sodium hydrogen carbonate .........................500 g
Tartaric acid .................................................430 g
II. Kollidon 25 [1]..................................................8 g
2-Propanol .................................................200 ml
III. Ascorbic acid, crystalline (BASF) ...................550 g
Sucrose (<0.5 mm) .......................................660 g
IV. Polyethylene glycol 6000, powder [6] ..............67 g
Dextrose, powder...........................................67 g
Orange flavour ...............................................10 g
Saccharin sodium ............................................1 g

2. Manufacturing (Wet granulation)
Granulate mixture I with solution II, pass through a 0.5 mm-sieve, and
dry at 60 °C. Dry mixture III also at 60 °C and mix together with I/II and
IV. At maximum 30 % relative atmospheric humidity, press to effervescent
tablets.

3. Tablet properties
Weight ...................................................2,300 mg
Diameter ....................................................20 mm
Form ........................................................biplanar
Hardness.....................................................100 N
Disintegration (water) ....................................2 min

BASF Fine Chemicals Generic Drug Formulations 1998

. powder (BASF) ...... 3..........06 % 15 kN 55 N 1 – 2 min < 0...........2.............. BASF Fine Chemicals Generic Drug Formulations 1998 .05 % 4............1 g 2. sieve and press to tablets of 335 mg weight...232 g Magnesium stearate [2] .. Manufacturing (Direct compression) Mix all components........ Influence of the compression force on the tablet properties compression force Property Hardness Disintegration Friability 7 kN 20 N 1 min 0....100 g Ludipress [1] .........9 Tablet formulations (Lab Scale) Vitamin C (Ascorbic Acid) Tablets (100 mg) 1................. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application...........05 % 22 kN 83 N 2 – 3 min < 0. Formulation Ascorbic acid.........

....................4 % Dissolution................1........> 90 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........................0 – 256...biplanar Hardness ................2 Magnesium stearate [2] ........0 Kollidon CL [1]..........2.25.... 3...........12 mm Form .............15. 30 min........................................ powder (BASF)..2.2 min Friability ........231..............0 Kollidon VA 64 [1] ..5 g g g g g g 2.. pass through a 0..............0..................200..................0 Ludipress [1]................................................................................................................................................................................. Formulation Ascorbic acid...............................9 Tablet formulations (Lab Scale) Vitamin C (Ascorbic Acid) Tablets (200 mg) 1................499 mg Diameter ....................................73 N Disintegration ........8 mm screen and press with medium compression force (18 kN).... Manufacturing (Direct compression) Mix all components......0 Aerosil 200 [4] ............ Tablet properties Weight ...............................................

9 Tablet formulations (Lab Scale) 80 Hardness Friability 70 60 50 40 Kollidon VA 64 Kollidon 30 BASF Fine Chemicals Generic Drug Formulations 1998 HP MC 11000 10 9 8 7 6 5 4 3 2 1 0 Friability [%] Hardness [kN] 4. Substitution of Kollidon VA 64 by other dry binders .2.

......2.... Formulation Ascorbic acid....................................... BASF Fine Chemicals Generic Drug Formulations 1998 ...........14 g Orange flavour ............196 g Stearic acid [7] .... powder (BASF).................500 mg Diameter ........................12 mm Form ..................................................................6 min Friability ....................................................................................................6 g Saccharin sodium .....................................3 g 2................................ pass through a 0.................0.... 3.......9 Tablet formulations (Lab Scale) Vitamin C (Ascorbic Acid + Ascorbate) Tablets (250 mg) 1..........3 g Aerosil 200 [4]..........................................................3 % 4................................. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application.............106 N Disintegration ........................................... Tablet properties Weight ........ Manufacturing (Direct compression) Mix all components...............208 g Ludipress [1] ..70 g Sodium ascorbate ...8 mm sieve and press with high compression force...................................biplanar Hardness...............................

...........9 Tablet formulations (Lab Scale) Vitamin C (Ascorbic Acid) Tablets (400 mg) 1..................................................................................... dry.........37........4 – 5 min Friability ..............75.........593 mg Diameter ... BASF Fine Chemicals Generic Drug Formulations 1998 ...........q........................110 N Disintegration ............................5 g Isopropanol............................ Ascorbic acid...............440................................................ Formulation I.. powder [6].biplanar Hardness ................. III...........5 g II.......0........ Tablet properties Weight ....................... Kollidon VA 64 [1] ..... pass through a 0............................5 g 2....12 mm Form ..........s................0 g Polyethylene glycol 6000.......2.......... Manufacturing (Wet granulation) Granulate mixture I with solution II......... Stability of appearance No change of the tablet colour during 3 months at 30 °C and 70 % relative humidity.................8 mm sieve.. Avicel PH 101 [5] ..... add III and press with medium to high compression force........................0 g Kollidon CL [1] . crystalline (BASF) . 3..........13.............3 % 4............4.........

.... 4......8 Liquid Formulations (Lab scale) Vitamin E + Benzocaine Solution (5 % + 2 %) 1............ Cool the clear solution to about 5 °C and dissolve Lutrol F 127............... Manufacturing Dissolve sorbic acid and benzocain in water at 60 °C........ Formulation Vitamin E acetate ........ Physical stability (22 °C and 40 °C) No change was observed after 2 months..........0.....................8 g g g g g g 2...............62.. viscous liquid.........5........................2 Water...... BASF Fine Chemicals Generic Drug Formulations 1998 ..0 Cremophor RH 40 [1]...............25.. add slowly the heated mixture of Vitamin E acetate and Cremophor RH 40 (60 – 65 °C).5............................ 3........5...........0 Sorbic acid ...................................... Properties of the solution Clear colourless...0 Benzocaine ..............2.....0 Lutrol F 127 [1] ....

....... 4........................... 3....22............ colourless liquid.. while they are still hot. BASF Fine Chemicals Generic Drug Formulations 1998 ..5....... Remark In Germany Cremophor EL must be declared on the package of injectables. Properties of the solution Clear or slightly opalescent.......0 g Preservative ....33 g Water for injectables ... they should be shaken for a short time.....8 Liquid Formulations (Lab scale) Vitamin E + Selenium Veterinary Injectable Solution (60 mg E + 3 mg Se/ml) 1... Vitamin E acetate (BASF) ............0 g Cremophor EL or Solutol HS 15 [1] .... Sterilization can also be performed by membrane filtration under pressure.6...s.. II.. stir well and add very slowly the hot solution II (60 °C).....ad 100 ml 2.0.......q....... Formulation I... to eliminate any separation of the phases that may have occurred................ Sodium selenite... Manufacturing Heat mixture I to about 60 °C............ After the ampoules have been heat-sterilized.......

..... BASF Fine Chemicals Generic Drug Formulations 1998 .....– granulated with 5 % Kollidon 30 Aerosil 200 [4] ...................... 1 No. 3 Vitamin E acetate SD 50 ..................12 min Friability .......... crystalline [10] ......................200 g (BASF) Ludipress [1]............................................. .106 N Disintegration .......2....biplanar Hardness .....– Sorbitol. Formulations No......................................................... 2 No...................................0 % 727 mg 12 mm biplanar 102 N 15 min 0% 624 mg 12 mm biplanar 68 N 17 min 0% 4............... Manufacturing (Direct compression) Mix all components..... 3 Weight ............12 mm Form ............ 3.. pass through a 0...........100 g Dicalcium phosphate [9]..8 mm screen and press with high compression force......390 g Mannitol .... 1 No.....711 mg Diameter ..... Tablet properties No........ 2 No......9 Tablet formulations (Lab Scale) Vitamin E Chewable Tablets (100 mg) 1...... Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application..3 g 200 g 200 g 493 g – – – – – – 400 g 7g – 4g – 2..................7 g Magnesium stearate [2] .........................

........8 mm sieve...............300........................................ Manufacturing (Direct compression) Pass all components through a 0..........0 SD 50 (BASF) Sorbitol [10].................................0 g g g g g 2.....0................620 mg Diameter .......... Formulation Vitamin E acetate dry powder .....9 Tablet formulations (Lab Scale) Vitamin E Chewable Tablets (150 mg) 1......0 Aerosil 200 [4] ..... mix and press with high compression force........ 3......................6.................................1% 4.......6............................< 0................................................300......80 N Disintegration (water) .0 Saccharin sodium.......12 mm Form ................................ Tablet properties Weight .......2................... BASF Fine Chemicals Generic Drug Formulations 1998 ..................biplanar Hardness.........................2 Magnesium stearate [2]......................> 30 min Friability .......... Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application........

................... Formulation Vitamin E acetate dry powder ..................................10.....................................................................610 mg Diameter . Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application............................................................................... Tablet properties Weight ....................biplanar Hardness..0 Aerosil 200 [4] .... BASF Fine Chemicals Generic Drug Formulations 1998 ...9 Tablet formulations (Lab Scale) Vitamin E Chewable Tablets (200 mg) 1................................................ 3.............1 g g g g 2.........................400.......12 mm Form .....67 N Disintegration (water) ..> 30 min Friability ...................... Manufacturing (Direct compression) Mix all components......0........0 SD 50 (BASF) Ludipress [1] ..2.200. pass through a 0.....0 Saccharin sodium ...........................................8 mm sieve and press with high compression force.0 % 4....

0 % 4......108 N Disintegration (water) ........... 3........................ BASF Fine Chemicals Generic Drug Formulations 1998 .................................................. Tablet properties Weight ..........s...........................q.....................> 30 min Friability ..9 Tablet formulations (Lab Scale) Vitamin E Chewable Tablets (400 mg) 1..........................................................800 g SD 50 (BASF) Ludipress [1] .................................. Manufacturing (Direct compression) Pass all components through a 0............. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application...............790 g Aerosil 200 [4] .... 2.....5 mm sieve..............665 mg Diameter .............................. mix and press with high compression force..1...................................... Formulation Vitamin E acetate dry powder...20 g Flavours .........................................biplanar Hardness ..............2..............20 mm Form ......

.8 Liquid Formulations (Lab scale) Vitamin E Concentrate.. 4.......... Properties of the solution Clear colourless liquid... Vitamin E acetate (BASF)... BASF Fine Chemicals Generic Drug Formulations 1998 ...q............... II....10.. Manufacturing Heat the mixture I and solution II separately to about 65 °C and add mixture I slowly to the well stirred solution II (or solution II slowly to mixture I).................. Water.. s......................0 g Preservative ............................... Formulation I...... Water-miscible (10 % = 100 mg/ml) 1................ 3..........5......25... Physical stability (20–25 °C) No change of appearance after 3 months..ad 100 ml 2.5 g Cremophor RH 40 [1].... miscible with water..

. Vitamin E acetate (BASF) ......0 g Preservative .........q.... Manufacturing Heat mixture I and solution II to about 65 °C and add solution II slowly to mixture I...... Properties of the solution Clear or lightly opalescent......5...8 Liquid Formulations (Lab scale) Vitamin E Drops (50 mg/ml) 1..........79...... Water ............ II............................. 3.......................16....... BASF Fine Chemicals Generic Drug Formulations 1998 ..... colourless liquid......... s..........0 ml 2.... Formulation I........0 g Cremophor RH 40 [1]...5.......

............................. Properties of the gel-cream Turbid white gel at temperatures between 20 – 50 °C. Physical stability After 2 weeks at 40 °C no changes of aspect or viscosity were observed.15 Lutrol F 127 [1] ..... BASF Fine Chemicals Generic Drug Formulations 1998 ................... Manufacturing Mix vitamin E acetate with propylene glycol and add the water..................... After cooling to about 6 °C dissolve slowly Lutrol F 127 in the well stirred mixture...........10 Propylene glycol Pharma [1] .. 3.6. 4.7 Formulations of semi-solid drugs (Lab scale) Vitamin E Gel-Cream (10 %) 1.......... Maintain cool until the air bubbles escaped.55 g g g g 2....... Formulation Vitamin E acetate (BASF) ...................... Viscosity at 25 °C about 120...........20 Water............000 mPa · s......

........38. BASF Fine Chemicals Generic Drug Formulations 1998 ..0 g Ethanol 96 % ...0 g 2.......4... Manufacturing Heat mixture I to about 60 °C...0 – 5................. Vitamin E acetate (BASF)......57.......0 g Water ..............8 Liquid Formulations (Lab scale) Vitamin E Solution with Ethanol (0...........01% = 1 mg/10 ml) 1.....10 mg Cremophor EL [1] ..... stir well and add slowly the warm solvent mixture II.............. Properties of the solution Clear. II.....5..... colourless liquid of low viscosity...................... Formulation I............ 3..............

...... 1 No..............140 g Tablettose [8] ...... Tablet properties No........................ crystalline (Merck) .......................................... Formulations No..... 2 Weight ...................9 Tablet formulations (Lab Scale) Vitamin E Tablets (50 mg) 1.........................................................10 g 100 g 300 g – – – 3g 3g 2...................................1% BASF Fine Chemicals Generic Drug Formulations 1998 ...15 g Magnesium stearate [2] .....1% 413 mg 12 mm biplanar 70 N 11 min < 0.2..biplanar Hardness .12 mm Form ...410 mg Diameter ......................< 0........................................................................................................................................100 g SD 50 (BASF) Sorbitol... 1 No..................................................................................... 2 Vitamin E acetate dry powder........9 min Friability ........ mix and press with high compression force...........................................8 mm sieve..................... Manufacturing (Direct compression) Pass all components through a 0..– Mannitol......................................34 N Desintegration ........... 3.........140 g Kollidon VA 64 [1] .......2 g Aerosil 200 [4] .

. BASF Fine Chemicals Generic Drug Formulations 1998 . 4.......8 Liquid Formulations (Lab scale) Vitamin K1 (= Phytomenadion) Injectable Solution (10 mg and 20 mg/ ml) 1...........0g q.. 87. Water for injectables ....0 g 2....0 g Solutol HS 15 or Cremophor EL [1]... After the ampoules have been heat-sterilized..... 1) Stored at 40 °C and protected from light the heat sterilized solution did not show any change of the clarity and colour after 12 weeks...... they should be shaken for a short time......0 g 11.... Formulation No.............. Remark In Germany Cremophor EL must be declared on the package of injectables... 1 No. The sterilisation can be done by heat at 120 °C or by filtration.. while they are still hot. Properties of the solution A clear colourless solution of low viscosity was obtained.............. Manufacturing Dissolve phytomenadion in Solutol HS 15 heated to about 60 °C and add slowly the warm water.......... 3.......... 2 Phytomenadion .. to eliminate any separation of the phases that may have occurred....1.............. Physical stability (Formulation No. Stored at 20 – 25°C in the day light the heat sterilized solution did not show any change of the clarity and colour after 12 weeks.......s. 5......q.....s.5....93..........0 g 2..6.5 g Preservatives ..........

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