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)

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). Water-miscible (10 % = 100 mg/ml) Vitamin E Drops (50 mg/ml) Vitamin E Gel-Cream (10 %) Vitamin E Solution with Ethanol (0. DC Vitamin B 1 Tablets (100 mg). II Vitamin B 1 Tablets (100 mg). I Vitamin B 1 Tablets (50 mg). 1. DC Vitamin B 6 Tablets (40 mg). 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).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. 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. 500 mg.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 .

Significant differences in the properties of the preparations may occur if the same active substance is used. The excipients mostly used in the formulations and their suppliers are listed in Table 1. the manufacturer’s name and the registered trademark are given for excipients. BASF Fine Chemicals Generic Drug Formulations 1998 . 1. Chapter 2. Since the manufacturer’s name was mostly not mentioned. For this reason.4 Active substances The active substances are almost exclusively generic. Thus. but has a different grain size or originates from another manufacturer. as necessary.1.5). They were mostly supplied free of charge as samples by pharmaceutical companies. scale-up for production must therefore be checked and revised. it unfortunately cannot be listed here.3 Size and optimization of the formulations All the formulations were developed exclusively on a laboratory scale of the order of 1 kg maximum. The reason for this is that the difference in physical properties may exert a strong effect particularly on solid drugs (cf. The serial numbers in the left-hand column of this table are quoted in the formulations.5 Excipients As far as possible. 1. the formulations are merely suggestions that require further optimization. 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.

PA 19103. USA Stearic acid Meggle Milchindustrie GmbH Postfach 40 83512 Wasserburg. Germany Polyethylene glycol 6000. Box 5439 675 McDonnel Boulevard St. powder Mallincrodt Inc.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.O. Germany Calcium arachinate Magnesium stearate [3] Cerestar GmbH Düsseldorferstrasse 191 47809 Krefeld. Germany BASF Fine Chemicals Generic Drug Formulations 1998 . P. Louis. MO 63134. Germany Potato starch Corn starch Degussa AG GB Industry + Fine Chemicals Postfach 1345 63457 Hanau. Germany Aerosil® 200 FMC Corp. Germany Lactose Monohydrate D 20 Tablettose ® [4] [5] [6] [7] [8] BASF AG Department MER 67056 Ludwigshafen. USA Avicel ® products Ac-Di-Sol ® Hüls AG Postfach 45674 Marl. Food + Pharmaceutical Products 735 Market Street Philadelphia.

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

Data on the chemical stability are often available for sensitive materials. PVP-iodine or vitamins. a.1. The formulations are practically always modified by the customer when they are scaled up to meet the demands of industry. Thus the final formulation must be checked in any event. The reasons are as follows. b. 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. The stability of the preparation may change as a result of items a.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. c. In view of the very number of formulations presented here and for capacity reasons. data are also listed on the physical stability. e. In a number of formulations. g. Aromas or colorants are added to the formulations in amounts depending on the particular taste of the target group. and b. BASF Fine Chemicals Generic Drug Formulations 1998 .

disintegrant. 1.2 Tablets 2. The limiting factors are the physical properties of the active substance and its concentration in the tablets (cf. particularly in the production of generics. It thus combines the properties of a filler. disintegration. This combination even allows 500 mg of paracetamol to be pressed into good tablets with a weight of 700 mg. 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). By virtue of its versatility formulations containing it are usually very simple. Plasticity.2 Direct compression The technology involved in direct compression assumes great importance in the tablet formulations. g. Ludipress and Kollidon VA 64. calcium phosphate. many analgetics. microcrystalline cellulose. Active substances. e.000 g of the mixtures to be tabletted were used. Kollidon 30. is an important parameter in direct compression. and a disintegrant. Ludipress. Normally. This limit may be shifted upwards by special direct compression auxiliaries. and chipping of the tablets and the data on their release are measured values. No other dry binder has a binding power and plasticity comparable to those of Kollidon VA 64. and the fraction of Ludipress required in the tablets is too large for paracetamol (= acetaminophen). 2. lactose. 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 %. that the active substance permits. ibuprofen requires a larger amount. hardness. e. g. or starch. e.000. this technique is not as suitable if the content of ascorbic acid is higher. However. binder.1 Size of formulations and measured values The formulations were developed on a laboratory scale in which case 200 –1. g. g.5). can be found in the BASF line of pharmaceutical excipients for direct compression. B. Ludipress Ludipress is a speciality derived from lactose. and Kollidon CL. The beneficial properties of Kollidon VA 64 can BASF Fine Chemicals Generic Drug Formulations 1998 . the amounts weighed out in the formulations correspond to the amount in the tablets multiplied by a factor of 1. The weight. As can be seen in Fig. e. Kollidon CL. Two important alternatives. because it is often the cheapest means. Kollidon VA 64 An alternative to Ludipress is the outstanding dry binder Kollidon VA 64 together with excipients. behave very differently with Ludipress when the dosage is extremely high. this property of Kollidon VA 64 is not adversely effected by increasing the pressure. viz. and flowability agent and also often acts as a release accelerator. in particular. Chapter 2. A. Acetylsalicylic acid and metamizole can be pressed when little Ludipress has been added.

The example of a placebo tablet illustrated in Fig. e.8 0. Substituting Kollidon 25 or Kollidon 30 by Kollidon 90 F would be particularly interesting for obtaining greater hardness without increasing the pressure.7 0. g.5 % binder + 0. 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. 2 shows that tablets of twice the hard- .Plasticity 1. Cellulose HPMC 11000 Plasticity = plastic energy/total energy Fig. e. Kollidon VA 64 and Ludipress can also be combined with one another.5 0. because direct compressing is not the most suitable technology for many active substances that are in high dosages or in fine powder form. Various alternatives to wet granulation in general are offered by BASF pharmaceutical excipients: Obviously. moistening. Fluidized-bed granulation was resorted to only in exceptional cases in view of the amounts needed. The granules for tabletting of the presented formulations were mostly produced by traditional means.9 0.0 Force: 18 kN Force: 25 kN 0.6 0. screening. Other alternatives consist of using different grades of Kollidon. – 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. drying. 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. eliminates all problems in wet granulation.4 Kollidon VA 64 Kollidon 30 Mc. and again screening. 1 Plasticity of dry binders in tablets (99. in a fluidized bed. modern equipment.3 Wet granulation Great significance is still attached to wet granulation. i.

2. 5 % Kollidon VA 64) BASF Fine Chemicals Generic Drug Formulations 1998 .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. Tablet Hardness (N) Conversely. 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. the same hardness is usually achieved by increasing the amount of Kollidon.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. 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.4 Tablet press All the formulations were devised on rotary tabletting presses that were fitted with 10 – 20 punches. 3 Direct compression of different types of ascorbic acid (40 % ascorbic acid. however. In practice.

....... 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 .......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..... 2..... Unfortunately........... 2. The release is determined by the methods laid down in the corresponding monographs for the tablets (usually USP) and in the prescribed medium.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.0 Povidone K 90 . Tablets of greater hardness are obtained if fine instead of coarse Povidone K 90 is taken...... 2.. but when the active substance consists of crystals of two different sizes (crystalline = > 150 µm........... Fig..... This is demonstrated in Table 2 in the light of the example of hydrochlorothiazide..... these data cannot be given for all formulations..physical properties of the active substance............. This particularly concerns the particle size.. If it is not stated to the contrary... 50..5 Magnesium stearate .5 Lactose monohydrate ...5 Water ......... 422. the disintegration time is measured in artificial gastric juice..... or USP).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 . 2.. 3 shows the difference that can occur when ascorbic acid tablets of the same composition are produced at the same pressure.6 Effect of the physical properties of the excipients Characterization of the physical properties of excipients is also important..Eur.... 37.... the disintegration and the release are also affected.. 7.. powder = < 150 µm)... To a certain extent..

BASF Fine Chemicals Generic Drug Formulations 1998 .in a time when this parameter was not yet demanded. 2.9 Formulations The formulations in this chapter have been arranged in the alphabetic order of their active substances.

for which the minimum amount of cores is 5 kg.5 Formulations The formulations in this chapter have been arranged in the alphabetic order of their function. these two are interchangeable. the conditions for processing the formulations on a given scale have been quoted.4 Colour additives Normally the colorants added were Sicovit colour lakes or Sicovit pigments. the fluidized-bed granulator WSG Glatt 15 or a traditional coating pan was used. 1 kg of spray solution or spray suspension and 5 kg of tablet cores.3 Conditions for spraying Whenever they are of importance. . 3.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. To a certain extent.3 Coating of tablets and capsules 3. 3. BASF Fine Chemicals Generic Drug Formulations 1998 3. In a few cases.2 Equipment The tests were mostly performed in the Accela-Cota 241. 3. The batches usually consisted of ca.

3 for details on the suspensions. powders.2 Methods of granulation The granules were mostly produced by traditional means. i. 4. 4. Larger batches. Fluidized-bed granulation was resorted to only in exceptional cases in view of the amounts needed. Normally the amounts used were those required for a trial of 50 – 500 g. The parameters that attracted most attention were the relative sediment volume (volume of sediment/total volume) and the redispersability. moistening. 4.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. e.3 Assessment of the properties of the granules Most of the cases concerned granules that were suspended in water before the administration. were only resorted to in exceptional cases. drying. the properties of the suspension thus formed were assessed. in fluidized-bed granulation. screening. and again screening. dry syrups and lyophilisates 4. BASF Fine Chemicals Generic Drug Formulations 1998 . See Chapter 5. Consequently.4 Formulations The formulations in this chapter have been arranged in alphabetical order of their active substances.4 Granules.g.e.

on the principle of hydrophilization. C Hydrophilization Typical fields of application are oilsoluble vitamins. mouth disinfectants. Micelle formation is certainly of minor significance. hexiditin. This may be affected by the molecular weight.5 Liquid preparations 5. Cremophor EL. A Microemulsions Cremophor RH 40. 5.000 g size. BASF Fine Chemicals Generic Drug Formulations 1998 . The longer the chains or the higher the K-value of the Kollidon type. The mechanism is probably based. antimycotics of the miconazole type. and clear solutions in water are thus obtained. The micelle that envelops the active substance is so small that it is invisible or perhaps visible in the form of an opalescence. BASF Pharmaceutical Excipients offer several possibilities and mechanisms. the stronger is the solubility effect and thus the greater the solubility that can be obtained by the active substance.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. In practice. and etherian oils or fragrances. and there is also a restriction on the amount to be used for each dose administered in intramuscular application.3 Stabilizing suspensions Various BASF pharmaceutical excipients with different functions can be used for stabilizing suspensions.2 Solubilization of insoluble active substances In order to solubilize insoluble lypophilic or hydrophobic active substances in an aqueous medium. this effect was mostly exploited for the solubilization of antibiotics in human and veterinary medicine. Details are given in the book “Kollidon – Polyvinylpyrrolidone for the pharmaceutical industry”. Active substances can also be solubilized by Lutrol F 68 in addition to the Cremophor and Kollidon products. 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. It is laid down in many countries that the K-value must not exceed 18. There are also restrictions on the use of this auxiliary in human parenterals. B Formation of complexing compounds The soluble Kollidon products form reversible complexes with many hydrophobic active substances. 5. The batches were of 50 –1. e. and Solutol HS 15 act as surfaceactive solubilizers in water and form the structures of micelles.g. for the most part.

g. B.1 Oral and topical suspensions The following groups of products can be offered for stabilizing oral and topical suspensions. of Kollidon 90 F suffice to stabilize aqueous suspensions.5 % in water) BASF Fine Chemicals Generic Drug Formulations 1998 . an effect that is consistent with the low viscosity. 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. which undergoes hardly any sedimentation. i. 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. e.5. Fig.). etc. 4 demonstrates that it can completely prevent sedimentation. which is only half of that of conventional crospovidone.3. % In this book. The addition of 5 – 9 % has practically no effect in changing the viscosity. 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. Soluble Kollidon products Low concentrations. The example taken was a crospovidone suspension. Kollidon CL. but strongly reduces the rate of sedimentation and facilitates the redispersability. 2 – 5 %. 4 Effect of Kollidon 90 F on the volume of sediment in a crospovidone suspension (7.e. surfactants. Kollidon 30 is also used for this purpose. A. It can be combined with all conventional suspension stabilizers (thickeners. 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. in particular. Relative sediment volume (24 h). One of the reasons for this Kollidon CL-M effect is its low (bulk) density. It can clearly be seen from Fig.

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

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

250 rpm) BASF Fine Chemicals Generic Drug Formulations 1998 . with the result that care must be exercised in scaling up from a laboratory to a production scale. The size of the batch was usually 100 g. 6. are intended as water-soluble base for suppositories and ovula. creams. viz.6 Semi-solid drugs (gels. gels are growing in importance in the pharmaceutical industry. This is often coupled with a guarantee of superior absorption. Lutrol E 400.3 Excipients as a base for suppositories and ovula 6. Lutrol E 1500. in contrast to pastes and creams. mixtures of the polyethylene glycols.4 Gel formers At the present time.1 Size of formulations and amounts used The formulations were developed on a laboratory scale. 6. C Fig. Lutrol E 4000. The BASF line of pharmaceutical excipients includes a gel former. and Lutrol E 6000. 6. because.2 Emulsifying agents in pharmaceutical creams Rel. suppositories and ovula) consistency of a cream. it can be visually ascertained that the active substance is dissolved. viscosity [mPa·s] The Cremophor types. 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. 6 Influence of the temperature on the consistency of 20 % Lutrol F 127 in water (rotary viscometer. They allow the production of physically stable formulations when they are used in low concentrations in the vicinity of 1 – 4 %. deg. 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.

Consequently. 6 that the gels are liquid at low temperatures i. The physical stability. was mainly determined on creams. BASF Fine Chemicals Generic Drug Formulations 1998 . A feature of these gels is their thermoreversible consistency. For the gels based on Lutrol F 127 the addition of 0. a gel reversibly exists whose consistency depends on the concentration of the Lutrol F 127. 6.polyoxamer Lutrol F 127. Data on the chemical stability are scanty. Preparations with PVP-iodine as disinfectant are an exception. below 15 °C and at temperatures above 75 °C. 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). In between these two values.2 % sorbic acid is recommended. No neutralization whatever is necessary. this point must be worked out in the final formulation.6 Stability 6. on applying heat at 45 °C. The formulations given in this chapter have been arranged in alphabetical order of their active substances.e. It allows the production of gels whose structures are stable in a pH range of 4 – 8.7 Formulations Preservatives and fragrances were not always added.5 Preservatives and fragrances 6. It is apparent from Fig.

5 Miglyol ® 812 (Dynamit-Nobel).1..................64.9............. Maintain cool until the air bubbles escaped. firm gel was obtained..9 Lutrol E 400 [1]..................... Lutrol F 127 [1] ..... Aceclofenac .4..........5 %) 1............... Manufacturing Mix the components I with water and cool to about 5 °C. Water..7 g g g g g 2... Properties of the gel A milky........ 3..............9 II........... Add slowly Lutrol F 127 and continue stirring until Lutrol F 127 is dissolved...........................9 Tablet formulations (Lab Scale) Aceclofenac Gel-Cream (1........................2.................. Formulation I.19.......0 III.......... BASF Fine Chemicals Generic Drug Formulations 1998 ...

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

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

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

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

... 1 Acetylsalicylic acid............................. 2 325 g 250 g – 100 g 12 g 30 g 3g 2....9 Tablet formulations (Lab Scale) Acetylsalicylic Acid + Vitamin C Tablets (325 mg + 250 mg) 1............................ Tablet properties No..............................................325 Ascorbic acid......................................40 Kollidon VA 64 [1] .............................8 mm sieve............................. crystalline [10] ...........250 Sorbitol..... 2 Weight ........................... Formulations No............ powder (BASF).120 Avicel PH 101 [5] ...................790 mg Diameter ...2 g g g g g g g No..92 N Disintegration .............2 min Friability .biplanar Hardness ......25 Kollidon CL [1] ....................................... 3....2.....................20 Magnesium stearate [2] . mix and press with medium/high compression force....................................................................................................................... Manufacturing (Direct compression) Pass all components through a 0...........12 mm Form ........ crystalline (Merck) ................1% 726 mg 12 mm biplanar 100 N < 1 min 1% BASF Fine Chemicals Generic Drug Formulations 1998 ................................... 1 No.............

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 % < 0.01% . Chemical stability of formulation No.4.01% < 0.01% < 0.

.............................................99 Stearic acid [7] .12 mm Form ........15 g g g g 2.................... Formulation Acetylsalicylic acid......97 % 4...............4 % Dissolution........................<1 min Friability....4 % 100..........90 N Disintegration .............................2.........................0 % 100...84 % 30 min ... pass through a 0................... 3..................... Chemical stability Storage time RT 40 °C 0 months 6 months 12 months 100.... Manufacturing (Direct compression) Mix all components............ Tablet properties Weight ..................400 Ludipress [1] ........................................ 15 min.... crystalline (Merck) ................. BASF Fine Chemicals Generic Drug Formulations 1998 ...................0 % 100.2 %........................8 mm sieve and press with low compression force...0 % 100.........................0.......516 mg Diameter ................0 % 98..................................biplanar Hardness......9 Tablet formulations (Lab Scale) Acetylsalicylic Acid Tablets (400 mg) 1....................0 % The content of free salicylic acid remained always below 0.....1 Kollidon CL [1].............................

........ 3................................................................8 mm sieve.. Tablet properties Weight ....................................0.... mix and press with low compression force.......25 Magnesium stearate [2] .......................12 mm Form ..15 Kollidon CL [1] ....500 Avicel PH 101 [5] ..................................................................2... Formulation Acetylsalicylic acid (Merck) ............7 % BASF Fine Chemicals Generic Drug Formulations 1998 ......... Manufacturing (Direct compression) Pass all components through a 0.................................9 Tablet formulations (Lab Scale) Acetylsalicylic Acid Tablets (500 mg) 1.............biplanar Hardness............................................<1 min Friability...........................3 g g g g g 2.707 mg Diameter .....200 Kollidon 30 [1] ........................................................................61 N Disintegration ......................................

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

...................3 Sorbitol..... Fill 50 g of the granules in a 100 ml flask (= dry syrup) or 5 g in sachets (= instant granules) 3.................................2 g g g g g g 2.... The suspension has no bitter taste........ Manufacturing Granulate mixture I with solution II......4.................. The obtained suspension has no bitter taste. dry syrups and Iyophylisates (Lab scale) Albendazole Dry Syrup or Instant Granules (200 mg) 1.......4 Formulation of granules. BASF Fine Chemicals Generic Drug Formulations 1998 . crystalline [10]. Albendazole ..... Instant granules (200 mg albendazole sachet): Suspend 5 g of the granules (= 200 mg albendazol) in a glass of water..22 Lutrol F 68 [1] ....88 Ethanol 96 % .....3 Sodium citrate..................... dry and sieve again..................8 mm screen.................................. Formulation I.............................. 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 ..... pass through a 0... II.........................................

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

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

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

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

..................1 g 2...8 mm screen and press with low compression force....................................................................148 g Magnesium stearate [2] .............biplanar Hardness .........5 g Ludipress [1] ..............0... Formulation Alprazolam........ BASF Fine Chemicals Generic Drug Formulations 1998 .....................................3 min Friability ......................... sieve through a 0..................1% 4.............8 mm Form .................5 mg) 1..........158 mg Diameter .....106 N Disintegration .................2................. Manufacturing (Direct compression) Mix all components........ Tablet properties Weight .................................................. 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........9 Tablet formulations (Lab Scale) Alprazolam Tablets (0........<0... 3..................................................

....about 50 III. dry......10 Lutrol E 6000 [1]......................................... mix with III and press with medium compression force..................................................23 Magnesium stearate [2] .. Aluminium acetylsalicylate ........... Kollidon CL [1] ..0....biplanar Hardness ................................110 N Disintegration.............................................................4 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................................... 3....... Formulation I...........8 mm sieve....... pass through a 0..........................................540 mg Diameter ....................................................................2...........255 Mannitol ...........12 mm Form ..28 II..........5 g g g g g g g g 2......... Kollidon 90 F [1] ............. Manufacturing (Wet granulation) Granulate mixture I with solution II.........213 Corn starch [3] ......................9 Tablet formulations (Lab Scale) Aluminium Acetylsalicylate Tablets (250 mg) 1...................................................1 – 2 min Friability............5 Isopropanol ............................................. Tablet properties Weight ........................

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

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 .

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

..........8 Liquid Formulations (Lab scale) Aluminium Hydroxide + Magnesium Hydroxide + Simethicone Suspension (8 % + 8 % + 0...........8 –10....................2....... s.......8............3....... Add emulsion I to the stirred suspension II and adjust the pH to about 9 with citric acid if needed....8.. Dissolve the flavours and saccharin in water and suspend aluminium hydroxide.......0 g Magnesium hydroxide..... heat to about 50 °C stirring well and add the warm water............................................ Aluminium hydroxide dry gel (Giulini) .........0 g Water ....White Aspect: . III......................5 g Saccharin sodium .............8 %) 1..Homogeneous....................................................................... Mix Cremophor RH 40 with simethicone.......0 g Sorbitol...............0.. crystalline [10] ........................................ to adust pH 9 2........................10........ Properties of the suspension Colour: ....................0 g II................. 3.....0 g Banana flavour ................. II....ad 100 ml III.......7................... Simethicone 30 % ....1 g Water...99 % BASF Fine Chemicals Generic Drug Formulations 1998 .....q.......... Manufacturing I........7 g Cremophor RH 40 [1] ..................0......5............ Citric acid ........... Formulation I...........4 g Coconut flavour........0 g Kollidon CL-M [1] ............... milky Relative sediment volume (1 day):............. magnesium hydroxide and Kollidon CL-M...0...

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

......... Manufacturing Mix Cremophor RH 40 well with the silicon oil....76... BASF Fine Chemicals Generic Drug Formulations 1998 ..............................8 Liquid Formulations (Lab scale) Aluminium Hydroxide + Magnesium Hydroxide Suspension (4 % + 4 %) 1..........5. Properties of the suspension There was only a slow sedimentation during storage and the redispersibility after weeks was excellent....................... 3....4.........0.......5...0 Magnesium hydroxide..............1 Kollidon CL-M [1]............................10......................... Formulation Aluminium hydroxide ..........0 Cremophor RH 40 [1] ......0 Silicon oil DC 200 (Serva) ....0 Water...4. add the water and suspend the solid substances...........9 g g g g g g 2..................

8 mm sieve and press with a compression force of 20 kN..................biplanar Hardness....................0 Ludipress [1] ......................................12..........16 mm Form .........0 Aerosil 200 [4] ... 3......................................6.................................................. Tablet properties Weight ...... pass through a 0..........................9 Tablet formulations (Lab Scale) Aluminium Hydroxide + Magnesium Silicate Chewable Tablets (120 mg + 250 mg) 1...0 Magnesium stearate [2]...640 mg Diameter ....... 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....232....6............................1................................................0 Menthol ..0 Magnesium trisilicate ...... Manufacturing (Direct compression) Mix all components.............. BASF Fine Chemicals Generic Drug Formulations 1998 .................250.............83 N 4...... Formulation Aluminium hydroxide dried gel (Giulini) .....................120..2.........5 g g g g g g g 2.................................0 Cyclamate sodium ...

......................... Formulation Ambroxol hydrochloride ............................................................0..... Manufacturing (Direct compression) Mix all components...............2.................217....................8 mm Form ...................... pass through a 0................. Tablet properties Weight ..82 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........2.................................................9 Tablet formulations (Lab Scale) Ambroxol Tablets (30 mg) 1.115 N Disintegration ........................5 g Magnesium stearate [2]............................biplanar Hardness ............30...........................5 g 2...........0 g Ludipress [1] ............. 30 min ..........2 % Dissolution.250 mg Diameter ........ 3.....7 min Friability.8 mm sieve and press with low compression force...................................................

.. mix with III.........80 N Disintegration ............ 1 No............ 2 Aminophylline............................... powder [6] ............5 mm sieve and press to tablets with medium compression force. Kollidon VA 64 [1]...............................................biplanar Hardness .179 mg Diameter .........................80 g Corn starch [3] ...................30 g III.......................................3 g Water ...8 mm sieve............2......... pass through a 0.........................– 90 g – 74 g 3g 3g 27 g – – 10 g I................ 3.3 – 4 min Friability ........................90 g Potato starch [3] .................. dry...........4 % BASF Fine Chemicals Generic Drug Formulations 1998 ..............................................– Kollidon VA 64 [1]........... Formulations No..9 Tablet formulations (Lab Scale) Aminophylline Tablets (90 mg) 1.......8 mm Form ...................................4 % 180 mg 8 mm biplanar 72 N 6 – 7 min 0.................... 2................. 2 Weight ........................0..3 g II...4 g Polyethylene glycol 6000.......... 1 No......................................... Magnesium stearate [2] ...........1 g Talc [10] .......................................................... Tablet properties No.. pass through a 0.................................................................................. hydrous powder (Knoll) ... Manufacturing (Wet granulation) Granulate mixture I with solution II.......

........biplanar Hardness ...... 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...............................12 mm Form ........2 % 4..... BASF Fine Chemicals Generic Drug Formulations 1998 ..... 3.......................1 – 2 min Friability.........12 g 2......................................9 Tablet formulations (Lab Scale) Aminophylline Tablets (100 mg)...... Tablet properties Weight ..................................................................................200 g Kollidon VA 64 [1] ............124 N Disintegration.......2...............................318 mg Diameter ..0.... sieve and press on a rotary press to tablets with low compression force....2 g Aerosil 200 [4] .....100 g Avicel PH 200 [5] ............................6 g Magnesium stearate [2] .. Formulation Aminophylline powder (Knoll) ................................ I 1....................................................................................................... Manufacturing (Direct compression) Mix all components...............

..97 N Disintegration..........................2 g g g g 2..................................................................... Manufacturing (Direct compression) Mix all components................................................................9 Tablet formulations (Lab Scale) Aminophylline Tablets (100 mg)........................................87 % 15 min: .. pass through sieve and press with low compression force................................................... 3...0.8 mm Form ........biplanar Hardness....100 % 4....... Tablet properties Weight ....... Formulation Aminophylline (Knoll) ............10 min Friability..... 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.................................... II 1........................ BASF Fine Chemicals Generic Drug Formulations 1998 ...............................................100 Ludipress [1] ..254 mg Diameter ...............2...................................................2 Magnesium stearate [2] ....................................150 Aerosil 200 [4] ..2 % Dissolution 10 min:.........

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

..... 4.......................0 Kollidon CL-M [1] ............... 3....4 g g g g g g g g g 2........0.............1 Sodium gluconate .......... Properties of the suspension The pH of the suspension is about 4.1...............4 Formulation of granules...................... The redispersibility is very easy after 2 weeks.. 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....0 Citric acid.....6...............9... Formulation Amoxicillin trihydrate.................5............... BASF Fine Chemicals Generic Drug Formulations 1998 ............. Manufacturing Mix all components and fill in a flask...........4................................ crystalline .....0 Sodium citrate............. dry syrups and Iyophylisates (Lab scale) Amoxicillin Dry Syrup (5 % = 500 mg/10 ml) 1.40...5........0 Orange flavour ..........5 Saccharin sodium....0 Sorbitol crystalline [10] ....................................0......................5. No sedimentation could be observed during more than 24 hours....5 Lemon flavour .........2..

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 .

......25 g Kollidon 12 PF [1] .. Formulation Amoxicillin sodium .. 1979.6...496. the dry content of an ampoule is mixed with 1..........9 ml of water to give a clear injection solution....495 + 0.4 Formulation of granules....... Beecham) 1.4... Manufacturing Dissolve the active ingredient in the well stirred solution of Kollidon 12 PF and after freeze-drying....00 ml 2..... fill 500-mg-portions of the dry lyophilisate into ampoules.7............. dry syrups and Iyophylisates (Lab scale) Amoxicillin Lyophylisate for Injection (250 mg) (according to Eur.......012... Patent 0......... BASF Fine Chemicals Generic Drug Formulations 1998 ..50 g Water for injections .....012.. Administration Prior to administration.........add 100..... 3.....

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

. Castor oil ......8 Liquid Formulations (Lab scale) Ampicillin + Cloxacillin Oily Suspension (1...........................5 g Cloxacillin sodium... BASF Fine Chemicals Generic Drug Formulations 1998 .5 g 2................. Add the components I and stir during cooling to room temperature... 4..3.. 3.............................. Remark The castor oil should not be heated to more than 50 °C because at higher temperature a strong thickening effect was observed.. Properties of the suspension A homogeneous suspension was obtained.......................... Formulation I............q....0 %) 1.. Manufacturing Heat the mixture III to 50 °C and dissolve II................. Lutrol F 68 [1]........ s...0 g III..................5................. Antioxidant..1.0 g II...............5 % + 4...... Ampicillin sodium ...91.4....

........... No sedimentation could be observed during more than 24 hours.......0...4 g g g g g g g g g 2.... Manufacturing Mix all components and fill in a flask.2...............5 Saccharin sodium.......... BASF Fine Chemicals Generic Drug Formulations 1998 ... The redispersibility is very easy after 2 weeks....... 3.............0 Orange flavour ......... Formulation Ampicillin trihydrate ...........................9..............4 Formulation of granules.....................4.............1 Sodium gluconate ....... 4............... dry syrups and Iyophylisates (Lab scale) Ampicillin Dry Syrup (5 % = 500 mg/10 ml) 1..........0 Sodium citrate..................................5 Lemon flavour .. Properties of the suspension The pH of the suspension is about 4............................0 Citric acid..............................6.......1..........0 Kollidon CL-M [1] .... crystalline .....5.5.......5.. 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........0.0 Sorbitol crystalline [10] .40......................

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 .4.

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

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

........... Formulation I.. heat to about 65 °C...5............. Anise oil ................34.......7 g Ethanol .............1......... 3.... Properties Clear or slightly opalescent............. Manufacturing Mix the anise oil with Cremophor RH 40.........8 Liquid Formulations (Lab scale) Anise Oil Solution (1%) 1..............................63.....s. colourless liquid....... stir strongly and add slowly the hot solution II.......q.................... BASF Fine Chemicals Generic Drug Formulations 1998 ....... II.................1... Water...3 g 2............0 g Cremophor RH 40 [1] .......0 g Preservatives..............................

........200 Parsley extract.................................................9 min Friability .....................200 Kollidon VA 64 [1] ...................................12 mm Form ....636 mg Diameter ........................... mix and press with low compression force....................... crystalline [10] ................................................. Manufacturing (Direct compression) Pass all components through a 0.0 % BASF Fine Chemicals Generic Drug Formulations 1998 ............ powder .......................biplanar Hardness.............. Formulation Asparagus extract.8 mm sieve.. Tablet properties Weight .........................................4 g g g g g g 2..................................20 Kollidon CL [1]........................................ powder ..................10 Magnesium stearate [2] .................9 Tablet formulations (Lab Scale) Asparagus Extract + Parsley Extract Tablets (200 mg + 200 mg) 1........ 3........................49 N Disintegration ............200 Sorbitol..........2...................

................biplanar Hardness.......................................14.............7 % BASF Fine Chemicals Generic Drug Formulations 1998 ....2... pass through a 0.........0 g Sorbitol............... Formulation Aspartame .66 mg Diameter .4 g Tartaric acid..............3 g Sodium bicarbonate.......................................7 g Kollidon 25 [1] .9 Tablet formulations (Lab Scale) Aspartame Effervescent Tablets (20 mg) 1................. crystalline [10] ....................... Manufacturing (Direct compression) Mix ................<1 min Friability.... Tablet properties Weight .....7 g Polyethylene glycol 6000....................................1................................................ 3.....................6 mm Form .................10.......5 mm sieve and press to tablets......1 g 2..............0..........................18...................1..............................25 N Disintegration .............20........ powder [6]........... powder ...................

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

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

..287.....................biplanar Hardness...........2........ 3..........................................................9 Tablet formulations (Lab Scale) Atenolol Tablets (90 mg) 1..............1% BASF Fine Chemicals Generic Drug Formulations 1998 .................................85 N Disintegration.9 g g g g g 2........................................12 mm Form .93......... Tablet properties Weight ................................ Manufacturing (Direct compression) Mix all components...........................................52.............................. pass through a 0....<0...................0 Magnesium stearate [2].........0..............2 – 3 min Friability ....2 Aerosil 200 [4] ...........0 Ludipress [1]..................0 Kollidon CL [1].............436 mg Diameter ................. Formulation Atenolol (Stober).....2........................8 mm sieve and press to tablets with low compression force..............................................

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

0 g Citric acid ..ad 100 ml 2. The bitter taste of Azithromycin is almost completely masked............................. Manufacturing Add the mixture I to the solution II and fill with water to a total volume of 100 ml shaking very well. 3......................................2.....5.....................5 g Chocolate flavour ................0 g Sucrose ...........................................................0.................8 Liquid Formulations (Lab scale) Azithromycin Suspension (5 % = 500 mg/10 ml) 1..........0 g II.............................. BASF Fine Chemicals Generic Drug Formulations 1998 .................. Cremophor RH 40 [1] ...........0.....................5.........60.0 g Sodium citrate.................9...10.0 g Kollidon CL-M [1] ................0 g III.....2 g Water ............. Properties of the suspensions Light-brown suspension showing no sedimentation during 24 hours and good redispersibility............. Formulations I............. Azithromycin dihydrate . Water....5.................

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

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

............... Add the water II to the obtained solution I with rigorous stirring.......................7 III.........................2 II.........2-propylene glycol... Cetylstearyl alcohol................ Propylene glycol [1] .. 3................... This basic cream was tested with different active ingredients soluble in 1...1.0....0 Cremophor A 6 [1] .....0 Active ingredient ....................7 Formulations of semi-solid drugs (Lab scale) Basic Cream for Different Active Ingredients 1.... Physical stability No change of appearance were observed during 6 weeks at 45 °C..................... Formulation I. Properties White cream.......67................0..........6.........1...... BASF Fine Chemicals Generic Drug Formulations 1998 ..7....8....5 Liquid paraffin ... Water .......12....... 4......................1 – 2........... Heat III until the active ingredient is dissolved......0 Parabene(s)......5 Cremophor A 25 [1] .. Manufacturing Heat the mixture I and the water II separately to about 80 °C. mix with I/II and continue to stir during cooling to room temperature..........................0 g g g g g g g g 2...8 – 69...

........ 1 No.................................5 1...........................................................................2.....5 0.................5 mm Form ........................5 g g g g 2..............– 5........................... 2 Weight ......................120 mg Diameter ................– Magnesium stearate [2] ..........................< 0................ 3.06 % 121 mg 5 mm biplanar 113 N 3 min 0.......................... 2 Benzhexol chloride ............114... Formulations No...........9 Tablet formulations (Lab Scale) Benzhexol Tablets (5 mg) 1...................... 1 No......0 g Corn starch [3] .biplanar Hardness. Manufacturing (Direct compression) Mix all components for 10 minutes in a turbula mixer and press with low compression force......0 14.......................4 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................120 N Disintegration ...........................7 min Friability .........................0 g 100..... Tablet properties No....0.......6 g Aerosil 200 [4]................0 g (= trihexylphenidyl hydrochloride) Ludipress [1]......................5............................

....40..................2 %) 1....8 g II..................................................... Manufacturing Prepare suspension II and let swell during one hour...............0 g Water............. Properties of the gel Colourless transparent gel......... BASF Fine Chemicals Generic Drug Formulations 1998 ......6........... Carbopol® 940 (Goodrich) .............1.................2 g Propylene glycol Pharma [1] .............0 g Triethanolamine .......0 g Water.......0 % + 0.....................0 g Kollidon 30 [1] ... natural (BASF) ...... Formulation I....40.........3..................... Alpha-Bisabolol....0........ Add this suspension to the well stirred solution I.....3..... Benzoyl peroxide ................ Add III.7 Formulations of semi-solid drugs (Lab scale) Benzoyl Peroxide + Alpha-Bisabolol Gel (5..0 g 2....1.0 g III...5........6...... 3......0 g Cremophor RH 40 [1] .....................

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

.......... 3.20.20......000 units + 200 mg/ml) 1............................ Procain benzylpenicilline .......0.....0..........5 % of cysteine could be added as antioxidant............... Remark To prevent of discolouration of Kollidon in the solution during storage 0.. BASF Fine Chemicals Generic Drug Formulations 1998 ............................ Water for injectables .....0 g Dihydrostreptomycin sulfate .................. add the components I to the well stirred solution II and pass through a colloid mill.ad 100 ml 2...................8 Liquid Formulations (Lab scale) Benzylpenicilline + Dihydrostreptomycin Injectable Suspension (200..5 g Carboxymethyl cellulose sodium .. 4.s....................5.0...2 to 0.... Formulation I...... II. Manufacturing Prepare solution II..6 g Parabene .....................0 g Kollidon 12 PF [1] .q. Properties A white homogeneous suspension was obtained.....5 g Sodium citrate............

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

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

..................................... powder (BASF) ......................................................................................... 1 (40 °C........................– Magnesium stearate [2] ........................... Manufacturing (Direct compression) Pass all components through o 0.100 g Vitamin E acetate dry powder 50 % ......................................60 N Disintegration (water) ....2...................... 2 Weight .................. Tablet properties No.65 g Ascorbic acid............... crystalline (Merck) ....................2 % 4..........7 min Friability .............................– Kollidon CL [1] .........6 g 65 g 100 g 60 g – 233 g 30 g 8g 4g 2. 3...................12 mm Form ......... Formulation No..................... mix and press with medium or high compression force....................8 mm sieve. 1 No.... closed) Beta carotene/tablet 0 weeks 15 weeks 80 mg 78 mg BASF Fine Chemicals Generic Drug Formulations 1998 .....................0...................... 2 Betavit ® dry powder 10 % (BASF) .................................................biplanar Hardness .60 g Ludipress [1] ..............3 % 502 mg 12 mm biplanar 59 N 7 min 0..... 1 No............................9 Tablet formulations (Lab Scale) Beta Carotene + Vitamin C + Vitamin E Tablets (6 mg + 100 mg + 30 mg) 1........369 g Sorbitol.– Kollidon VA 64 [1]..........599 mg Diameter ........... Chemical stability of beta carotene in Formulation No..............

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

.....240 g Kollidon CL [1] ........497 mg Diameter ............ Formulation Betavit® dry powder 10 % (BASF) ............. 3.................. Remarks A colourant pigment should be added to obtain a homogeneous appearance of the tablets............8 min Friability ................... powder (BASF).......... These tablets could be commercialized in Europe as dietary food because all components are allowed for this application..55 N Disintegration ............< 0.................. Tablet properties Weight ...............................8 mm sieve..........................75 g Ascorbic acid.............................................60 g Vitamin E acetate dry powder 50 % .1% 4.........50 g Sorbitol..... mix and press with low compression force......................................30 g Magnesium stearate [2] .........12 mm Form ..... BASF Fine Chemicals Generic Drug Formulations 1998 .............. crystalline [10] ..................................................... Manufacturing (Direct compression) Pass all components through a 0.2.biplanar Hardness..9 Tablet formulations (Lab Scale) Beta Carotene + Vitamin C + Vitamin E Tablets (7 mg + 60 mg + 25 mg) 1.........................................................5 g 2.....................

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

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

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

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

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

..................... 3........................00 Lutrol F 127 [1] .......13 Neomycin sulfate .ad 100.............. Mix both solutions....0........6. Formulation Betamethasone valerate ..1% + 0.............. Manufacturing Dissolve betamethasone valerate in the mixture of Lutrol E 400 and Miglyol 812...... Properties of the gel-cream A milky white soft gel-cream is obtained...6 %) 1...65 Lutrol E 400 [1] ...................20........ BASF Fine Chemicals Generic Drug Formulations 1998 ..........................00 Water ........... Dissolve Lutrol F 127 and neomycin sulfate in water at 5 –10°C..10............00 g g g g g g 2............15.......0.7 Formulations of semi-solid drugs (Lab scale) Betamethasone + Neomycin Gel-Cream (0......00 Miglyol ® 812 (Dynamit-Nobel) . Maintain cool until the air bubbles disappeared.

Add the water II to the obtained solution I with rigorous stirring... Physical stability No change of appearance or crystallization were observed during 6 weeks at 45 °C............ Remark This formulation could be used for other active ingredients too.1.............0.7 Formulations of semi-solid drugs (Lab scale) Betamethasone Cream (0...........................................................1 g g g g g g g g 2....0.........12.. Water............................. Properties White cream......... Cetylstearyl alcohol..0 Cremophor A 6 [1] ....8......... BASF Fine Chemicals Generic Drug Formulations 1998 ......... Heat III until the active ingredient is dissolved... Manufacturing Heat the mixture I and the water II separately to about 80 °C......7 III......1....7.........5 Liquid paraffin . Propylene glycol [1] ...........................1%) 1......5 Cremophor A 25 [1] .....6...... 5................ Formulation I.................................. 4............2 II..0 Parabene(s)..... mix with I/II and continue to stir during cooling to room temperature.......... 3........69.........0 Betamethasone .........

............... Formulation I......0......20.........0 Propylene glycol Pharma [1] ...........0 g g g g g 2................ Mix both solutions.. Betamethasone valerate ..7 Formulations of semi-solid drugs (Lab scale) Betamethasone Gel (0...0 Water .10.. 3...22....... Properties of the gel The obtained gel is clear and colourless.... BASF Fine Chemicals Generic Drug Formulations 1998 .....................0 Lutrol F 127 [1] ..1 Ethanol 96 % ... Maintain the temperature until the air bubbles disappeared.......... Manufacturing Prepare the solution I at room temperature and solution II at about 6 °C (or at > 70 °C)......1%) 1......... 4. II.................... Remark Perhaps a certain amount of propylene glycol could be substituted by water...........................47..........6....

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

...2...................................................200 Kollidon 30 [1] .......................................................3 min Friability.........................................................................0.....5 Aerosil 200 [4] ................................................................... These tablets could be commercialized in Europe as dietary food because all components are allowed for this application......477 mg Diameter ........4 % 4................................................ the hardness of tablet is higher but the content uniformity is less..... BASF Fine Chemicals Generic Drug Formulations 1998 ......4 g g g g g 2...4 Magnesium stearate [2] ........... 3.250 Ludipress [1] ................. Tablet properties Weight .................12 mm Form . pass through a sieve and press with medium compression force...... DC 1... Remark If the bran is not milled...... Formulation Bran wheat (milled <1 mm)...................52 N Disintegration ............. Manufacturing (Direct compression) Mix all components.....biplanar Hardness...........9 Tablet formulations (Lab Scale) Bran Tablets (250 mg)..................................................

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

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

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

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

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

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

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

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

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

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

.......... Tablet properties Weight ...........9 Tablet formulations (Lab Scale) Carbamazepine Tablets (200 mg) 1....8 mm sieve and press with low compression force....................biplanar Hardness ......0..................3 % Dissolution 10 min:........ 3...................1 min Friability........................................86 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................................................................................200 g Ludipress [1] ........................................................496 mg Diameter ...............128 N Disintegration ............. Manufacturing (Direct compression) Mix all components........................................................................... pass through a 0......2.....................83 % 60 min: ....300 g Magnesium stearate [2] ....12 mm Form ..... Formulation Carbamazepine .............................2 g 2.........................................75 % 30 min: ..........................

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

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

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

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

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

........8 Liquid Formulations (Lab scale) Chloramphenicol Ophthalmic Solution (3 %) 1......................... Water ...0 g Kollidon 25 [1] .....s...... Properties Clear colourless solution having a low viscosity.........5 % of cysteine could be added as antioxidant..................... 3...3....... Remark To prevent of discolouration of Kollidon in the solution during storage 0. dissolve Kollidon 25.0 g 2... add chloramphenicol and stir until a clear solution is obtained................... 4...... BASF Fine Chemicals Generic Drug Formulations 1998 ..... cool.............2 to 0.0 g Preservative ...5.............add 100........q..15. Manufacturing Dissolve the preservative in hot water.................... Formulation Chloramphenicol .....

....... Cool to 40 °C and add this solution slowly to the well stirred solution II..... crystalline ................ad 100 ml 2..... Chloramphenicol palmitate...............................................40.5 % = 250 mg/10 ml) 1..............0 g III......5 g Lutrol E 400 [1]..................0 g II....2. Properties White. 3..5...... Water........8 Liquid Formulations (Lab scale) Chloramphenicol Palmitate Oral or Topical Emulsion (2..........40................. Manufacturing Mix components I at 70°C to obtain a clear solution..... BASF Fine Chemicals Generic Drug Formulations 1998 .... homogeneous emulsion without foam formation......0 g Water.......... Formulation I..0 g Cremophor RH 40 [1] .........4. Sucrose. Fill up with III to 100 ml...................................4........

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

3.. BASF Fine Chemicals Generic Drug Formulations 1998 ............................ Formulation Chlorhexidin diacetate .............. Properties of the gel A clear colourless gel is obtained.....7 Formulations of semi-solid drugs (Lab scale) Chlorhexidine Gel (2 %) 1....... Physical stability (4 months....... 40 °C) No change of the appearance.........22 Water... Manufacturing Dissolve chlorhexidin diacetate in propylene glycol at > 70 °C.......................... stir well and add slowly Lutrol F 127 and water..30 Lutrol F 127 [1] ...........6.........46 g g g g 2............. Maintain the temperature until the air bubbles escaped....2 1. 4.................2-Propylene glycol Pharma [1] ...

........... Kollidon VA 64 [1] .. 5.........................................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ........................................................................................ 5............. 8 mm Form .........0 Sorbitol...............2....... pass through a 0.... 5.............. biplanar Hardness............... 0.. 150...... crystalline [10] .8 mm sieve and press with medium compression force................................... 2.0 Eucalyptol..... Formulation Chlorhexidine (Sigma) .............9 Tablet formulations (Lab Scale) Chlorhexidine Lozenges (5 mg) 1...........................................0 Aspartame............................................ 63 N Disintegration. 1........................ sodium ................. 5... potassium .................... 1................................................................0 Menthol........0 g g g g g g g g g 2.0 Magnesium stearate [2] .........0 Saccharin...... crystalline .... 3... Tablet properties Weight........... Manufacturing Mix all components. 0... crystalline ............ 175 mg Diameter ..... > 10 min Friability ............1 Aerosil 200 [4] ............

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

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

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

.........92 N Disintegration .............................9 Tablet formulations (Lab Scale) Cimetidine Tablets (200 mg) 1........12 mm Form ......5 g 2............................... Manufacturing (Direct compression) Pass the mixture through a 0....biplanar Hardness...................................0.....................................200 g Ludipress [1] ...................................88 % BASF Fine Chemicals Generic Drug Formulations 1998 .510 mg Diameter ....................................................... Formulation Cimetidine..2.8 mm screen and press with low compression force.................2 % Dissolution (15 min) .................. 3......................................................................................................... Tablet properties Weight .........................................295 g Magnesium stearate [2] ..1 min Friability..................

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

.................100 % BASF Fine Chemicals Generic Drug Formulations 1998 ..........400 Corn starch [3] .................. Cimetidine........ add III and press to tablets with low compression force..........................biplanar Hardness.............................91 N Disintegration ......................................... pass through a 0.8 mm sieve............0....9 Tablet formulations (Lab Scale) Cimetidine Tablets (400 mg) 1..62 % (20 min) .........100 III........ Tablet properties Weight ...................2....................................91% (30 min) ..601 mg Diameter .................................................................................. Formulation I....................................................20 Water .......................... 3...............12 mm Form ..................................5 % Dissolution (10 min) ......3 g g g g g 2.......4 min Friability...........170 II.......................... Kollidon VA 64 [1] ............................... Magnesium stearate [2] .............................................................................. Manufacturing (Wet granulation) Granulate mixture I with solution II......

.2..........biplanar Hardness.........................................0..........02 g Ludipress [1] ............................... BASF Fine Chemicals Generic Drug Formulations 1998 ..........00 g 2......... Formulation Clenbuterol hydrochloride .... Manufacturing (Direct compression) Mix all components in a turbula mixer and press to tablets with a compression force of 20 kN....... 3.......3 min 4.................100 mg Diameter ........ Tablet properties Weight .............................................75 N Disintegration . 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...1.....................................................8 mm Form .....................................................99..............00 g Magnesium stearate [2].........9 Tablet formulations (Lab Scale) Clenbuterol Tablets (20 µg) 1.........

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

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

..0 g Sodium hydroxide........ Manufacturing Dissolve Closantel in solution II and add solution III.....0 g Kollidon 12 PF or Kollidon 17 PF [1] ....... formation of oedemas) and to increase the retention time in the tissue.5...g....ca.. Closantel ..01 – 0..0....... Sodium bisulfite ............ II.... Remarks The function of Kollidon 12 PF or Kollidon 17 PF is to reduce strongly the local side effects (e. 60 g III................ BASF Fine Chemicals Generic Drug Formulations 1998 ... 20 g 2...0 g Propylene glycol Pharma [1] .8 Liquid Formulations (Lab scale) Closantel Veterinary Injectable Solution (12 – 20 g/100 ml) 1......12.04 g Water for injectables ..ca...... 50 % in water ..5 – 3......... The sterilisation can be done by heating (120 °C......... Formulation I.. Properies of the solution Clear yellow solution 4...2...0 – 20....0 –12.9........... 20 min) 3...

................................................... viscous liquid...............................8 Liquid Formulations (Lab scale) Clotrimazol Topical Solution (3 %) 1..............0 g Cremophor RH 40 ...................34 g Water... Ethanol 96 % ...... BASF Fine Chemicals Generic Drug Formulations 1998 ..q..... Formulation I.0 g Preservative ....... s..... colourless...............5...........3........ Properties Clear.......... II...............30.33 g 2.... Clotrimazol.... 3.............. stir strongly and add slowly the hot solution II...... Manufacturing Dissolve Clotrimazol in Cremophor RH 40 at about 60 °C............

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

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

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

... 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................................................8 mm Form ......... 3 min Friability..................... Manufacturing (Direct compression) Pass all ingredients through a 0...... 3................... Tablet properties Weight .......2.............................................. Mix and press with very low compression force (4 kN)............................................202 mg Diameter .......................... Formulation Cyproheptadine ............................2 g 2.............biplanar Hardness.. BASF Fine Chemicals Generic Drug Formulations 1998 .........8 mm sieve....0......9 Tablet formulations (Lab Scale) Cyproheptadine Tablet (4 mg) 1.........................................4 g Ludipress [1] .........................................194 g Magnesium stearate [2] ......46 N Disintegration ...............................5 % 4........

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

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

9 Tablet formulations (Lab Scale) Diazepam Tablet (10 mg) 1.........................100 % BASF Fine Chemicals Generic Drug Formulations 1998 .. Formulation Diazepam..................................................................... Tablet properties Weight ..................according to the formulation Form ........................................10 g Ludipress ..........< 0............100 – 480 g Magnesium stearate ..........110 – 490 mg .........biplanar Hardness ........2...< 5 min Friability ...> 100 N Disintegration ............1% Dissolution (10 min) ...............................5 – 2.................................................. 3.......... pass through a 0.8 mm sieve and press with medium compactation force................................0 g 2.............. Manufacturing (Direct compression) Mix all components.......0.............................................

.. Formulation Diclofenac sodium ....................................6................20 Lutrol F 127 [1] .. BASF Fine Chemicals Generic Drug Formulations 1998 ........7 Formulations of semi-solid drugs (Lab scale) Diclofenac Gel (1%) 1.22 Water....... 3........ 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....................1 Propylene glycol Pharma [1] ...................57 g g g g 2................................... Properties Colourless clear gel.......... Maintain the temperature until the air bubbles disappeared....

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

...................0 g Kollidon 17 PF [1] ..8 Liquid Formulations (Lab scale) Diclofenac Injectable Solution (75 mg/3 ml) 1.. The sterilisation could be made by aseptic filtration (0.....0 g Benzyl alcohol .......5.... benzyl alcohol and water................ BASF Fine Chemicals Generic Drug Formulations 1998 ...to 300 ml 2............7..............2 µm).............. Manufacturing Dissolve Kollidon 17 PF in the mixture of propylene glycol.. Formulation Diclofenac sodium ..........................12............... add diclofenac sodium and stir until a clear solution is obtained...0 g Water for injectables.5 g Propylene glycol Pharma [1] ................5.....50.......

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

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

.....0 g Kollidon CL [1] ....150..................................................15.... Tablet properties Weight .. pass through a 0................................2.................................................................10............................................................. 3......... Manufacturing (Direct compression) Mix all components.........................................8 mm Form ...........................77 % (30 min)........0 g Ludipress [1] .................................. powder [6] ..1............58 % (15 min) ................................0 g Magnesium stearate [2]............biplanar Hardness.....5 g Polyethylene glycol 6000..16 min Friability ....................72 N Disintegration .... Formulation Diclofenac sodium ...................8 mm sieve and press with low compression force........<0.............................................50...........9 Tablet formulations (Lab Scale) Diclofenac Tablets (50 mg) 1.........................0 g 2.......226 mg Diameter .1% Dissolution (10 min) .......99 % BASF Fine Chemicals Generic Drug Formulations 1998 ....

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

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

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

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

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

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

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

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

.............2...............112 mg Diameter ...........2 min Friability .........9 Tablet formulations (Lab Scale) Ethambutol Tablets (800 mg) 1............. Formulation I................................8 mm sieve..........20 mm Form ..........................................q.............................. DI-TAB [9] ..........30 g Isopropanol ........... pass through a 0.1% BASF Fine Chemicals Generic Drug Formulations 1998 .................................. Ethambutol (Helm) ................ Kollidon CL [1] ......................... Tablet properties Weight ....................................................................s.......200 g II........oblong Hardness....... dry.... add III and press with high compression force. Kollidon 30 [1] ....15 g 2.....1...................................78 N Disintegration ....... Manufacturing (Wet granulation) Granulate mixture I with solution II............................50 g Magnesium stearate [2]...................... 3.............................1....... III..800 g Dicalcium phosphate..............

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

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

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

....... 2 Weight ..............3 min Friability.......................... Tablet properties No........2....................3 % not tested not tested BASF Fine Chemicals Generic Drug Formulations 1998 ......................– Aerosil 200 [4]..............................<0.................................... Formulations No..................8 mm sieve and press with low compression force...........40 g Ludipress [1] ..63 % (30 min) ...1% Dissolution (10 min).8 mm Form ...............................................9 Tablet formulations (Lab Scale) Famotidine Tablets (40 mg) 1....................................................................149 mg Diameter ...105 g Magnesium stearate [2] ...... 3........................................................................ Manufacturing (Direct compression) Mix all components...... 1 No........................................3 g Stearic acid [7] ......... 2 Famotidine..4 g 40 g 104 g – 2g 4g 2......74 N Disintegration (gastric juice).................................................................biplanar Hardness ................... pass through a 0................................................. 1 No...............95 % 148 mg 8 mm biplanar 49 N 1 min 0..........................

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

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

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

...........0 Camphora.... 3...........................................5.......40............ Properties of the solution Clear or slightly opalescent liquid............ Manufacturing Mix the active ingredients with Cremophor RH 40 and heat to 50 – 60 °C....45......................7 g g g g g 2.3 Water.5....3........ 4........... Formulation Fir needle oil (Frey & Lau) .....................0 Cremophor RH 40 [1] ...... Add the ethanol and slowly the warm water to the well stirred solution...........0 Ethanol 96 % ....... Remark The needed amount of Cremophor RH 40 depends on the type of fir needle oil...............8 Liquid Formulations (Lab scale) Fir Needle Oil Solution (3 %) 1......6. BASF Fine Chemicals Generic Drug Formulations 1998 ........

.......213 mg Diameter .....1% 4.....................195............................................................205 N Disintegration ........................................ BASF Fine Chemicals Generic Drug Formulations 1998 ........5 g 2.....< 0...........................0 g Ludipress [1] .. Tablet properties Weight .. Formulation Folic acid .................... pass through a 0.........9 Tablet formulations (Lab Scale) Folic Acid Tablets (5 mg) 1......... 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.....8 mm Form .............. Manufacturing (Direct compression) Mix all components....................7 min Friability ......1..........biplanar Hardness........................5........0 g Magnesium stearate [2].. 3...........................8 mm sieve and press to tablets with medium compression force.........................................................

. add the mixture III and press with low compression force.............3 g Magnesium stearate [2]......................................... Formulation I.55 N Disintegration .....biconvex Hardness........63....6........2.. Remark To accelerate the disintegration the amount of Kollidon 90 F should be reduced and Kollidon CL should be applied in intra............................ Fucidine ........ pass through a 0........ Tablet properties Weight ......................and extragranular form.......................25 min Friability ...9 Tablet formulations (Lab Scale) Fucidine Tablet Cores (125 mg) 1..................................................0 g 2. dry..................5 g Isopropanol ........................ Kollidon 90 F [1] ..3....9 mm Form ........ 3.................................................................2 g Aerosil 200 [4] ........125.......................................................................2................. Kollidon CL [1] .... Manufacturing (Wet granulation) Granulate mixture I with solution II.....200 mg Diameter ........... DI-TAB [9] ...0 g Dicalcium phosphate............................................1........................ BASF Fine Chemicals Generic Drug Formulations 1998 ...0 % 4.............30 ml III.....0 g II...........8 mm sieve....

. BASF Fine Chemicals Generic Drug Formulations 1998 .......2 to 0. Formulation Furaltadone....00 g Tartaric acid .... Remark To prevent of discolouration of Kollidon in the solution during storage 0..ad 100 ml 2.......25............. 20 min)...............5........00 g Water of injectables .....25 g Kollidon 12 PF [1] ......... 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....................5 % of cysteine could be added as antioxidant.1.8 Liquid Formulations (Lab scale) Furaltadone Injectable Solution (50 mg/ml) 1.. 3...............................

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

.....200 Ludipress [1] ............. 3......618 mg Diameter ................................3 – 4 min Friability....2 % BASF Fine Chemicals Generic Drug Formulations 1998 .............................6 Aerosil 200 [4] .................................. pass through a 0..............................................0.12 mm Form ...........................388 Magnesium stearate [2] .....2............................................8 mm sieve and press with low compression force........................................ Formulation Furosemide ..........biplanar Hardness ... Manufacturing (Direct compression) Mix all components................159 N Disintegration ............................................................ Tablet properties Weight ........................................................9 Tablet formulations (Lab Scale) Furosemide Tablets (200 mg) 1...............6 g g g g 2..........

BASF Fine Chemicals Generic Drug Formulations 1998 ................. Formulation I............................... Kollidon 30 [1] ..... pass through a 0.3 % 4................. Tablet properties Weight ........23 min Friability..... Calcium phosphate............................... Manufacturing (Wet granulation) Granulate mixture I with solution II............312 mg Diameter ...............2 g g g g g g 2.98 N Disintegration .....0.......................................8 mm sieve............................................................2...biconvex Hardness..................................................... add III and press with low compression force..............94 II................... dibasic [9] ......... Dried garlic powder ........................................95 Lactose monohydrate [8] ................................................ 3......................9 Tablet formulations (Lab Scale) Garlic Tablets Cores (100 mg) 1..................... Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application....25 III.9 mm Form .............................100 Magnesium stearate [2] ..9 Water...

pass through a 0.........8 mm sieve and press with low compression force (about 10 kN).......... 2 Glibenclamide micronized (Guidotti)...........5 g – 5......2..... Tablet properties No..0 g 194...............................7 mm Form ...........................0 g 2..0 g Glibenclamide .................................0 g Magnesium stearate [2] ............................ 3................... Formulation No.................................................– Ludipress [1] ..................... 1 No........< 0...biplanar Hardness ..........69 % (60 min) ....5...........120...................................1% – – – BASF Fine Chemicals Generic Drug Formulations 1998 .......................50 % (30 min) ........................................0 g 1.........80 N Disintegration ......75 % 201 mg 8 mm biplanar 107 N 3 – 4 min < 0................ Manufacturing (Direct compression) Mix all components............................. 1 No.............0...........125 mg Diameter .2-3 min Friability ..2 % Dissolution (10 min)................................................... 2 Weight ..................................9 Tablet formulations (Lab Scale) Glibenclamide Tablets (5 mg) 1.........................................

1% Compression force 10 kN 20 kN 107 N 3 – 4 min < 0.1% .4.1% 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. 2) Property Hardness Disintegration Friability 5 kN 47 N 2 – 3 min < 0.

...8 mm sieve and mix with III.... Kollidon 30 [1] ...................... 3............................................573 g Sorbitol.................................11 g Magnesium stearate [2] .....................................719 mg Diameter ............................ Tablet properties Weight...................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ........ Formulation I...................138 N Disintegration ... Press with low compression force to tablets.............................................................................2.0.s.....6 min Friability. pass through a 0............................biplanar Hardness .........115 g II....................... Manufacturing (Wet granulation) Granulate mixture I with solution II...17 g Water........2 g 2...........................q....... dry.............. III........................ Glutaminic acid .... Kollidon CL [1] .........12 mm Form ...................9 Tablet formulations (Lab Scale) Glutaminic Acid Tablets (550 mg) 1... crystalline [10] ................................................................

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

......... BASF Fine Chemicals Generic Drug Formulations 1998 ........................................9 Tablet formulations (Lab Scale) Griseofulvin Tablets (125 mg) 1..............................3 % Dissolution.............78 % 40 min ..................5 mm sieve.......... micronized (Aldrich) ...................................88 % 60 min ............... 3... Remark The flowability of the tabletting mixture should be increased by higher amounts of Ludipress or/and Aerosil 200....92 % 4..........................10 g Aerosil 200 [4] .... powder [6] ..........biplanar Hardness............................12 mm Form ....................................................... Tablet properties Weight .....79 N Disintegration ........................19 g 2.........................................................1 min Friability..........2............................0....367 mg Diameter .... mix and press with low compression force applying a vibrating hopper.......... Manufacturing (Direct compression) Pass all components through a 0....................................... Formulation Griseofulvin..... 20 min ...........250 g Polyethylene glycol 6000..125 g Ludipress [1] ....................

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

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

........q.......75 N Disintegration. Formulation I. 3...............................................489 mg Diameter ............ 2............................................ Tablet properties Weight ............................... Manufacturing (Wet granulation) Granulate the extract I with solution II..........................12 mm Form ..about 120 g III..........................................biplanar Hardness.........2 % BASF Fine Chemicals Generic Drug Formulations 1998 ................. II...................................2 – 3 min Friability.............. Horsetail extract................8 mm sieve......0.......................................2.... mix with III and press with high compression force.......14 g Lutrol F 68 [1] ................ dry............................... Kollidon CL [1]..........s.........5 g Isopropanol ..9 Tablet formulations (Lab Scale) Horsetail Extract Tablets (450 mg) 1...14 g Magnesium stearate [2]................................................ pass through a 0. powder .................456 g Kollidon VA 64 [1] ...............

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

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

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

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

8.. Heat III until the active ingredient is dissolved....... Remark This formulation could be used for other active ingredients too.0 Hydrocortisone............. mix with I/II and continue to stir during cooling to room temperature.... 5................ Properties White cream.............................1.. 4.... Cetylstearyl alcohol........6............ 3.5 Cremophor A 25 [1] ................. Physical stability No change of appearance or crystallization were observed during 6 weeks at 45 °C........1...................2 II...........................12.68.7 Formulations of semi-solid drugs (Lab scale) Hydrocortisone Cream (1%) 1.......... Manufacturing Heat the mixture I and the water II separately to about 80 °C... Formulation I....................5 Liquid paraffin ............................0 Parabene(s)...............0 g g g g g g g g 2............................0.........0 Cremophor A 6 [1] ............................ BASF Fine Chemicals Generic Drug Formulations 1998 .1........8 III..............7. Propylene glycol [1] ... Water... Add the water II to the obtained solution I with rigorous stirring.

.. Formulation I............................6 Ethanol 96 % ......7...........7 Formulations of semi-solid drugs (Lab scale) Hydrocortisone Ethanolic Gel (0.......6.......... II............60.......0 Carbopol 940 (Goodrich) .5 Water.......5 Cremophor RH 40 [1] .......... BASF Fine Chemicals Generic Drug Formulations 1998 .0... Manufacturing Prepare solution II and mix slowly with solution I.....9 Water ..................5 g g g g g g g 2........................................0......... Hydrocortisone acetate....................24.............................. Properties Clear......0 Triethanolamine ..................... colourless gel.............0........5 %) 1...... 3...........6..

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

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

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

................. suspend Kollidon CL-M and ibuprofen in this solution by stirring and add the rest of water................25 g Kollidon CL-M [1] ..................................................8 Liquid Formulations (Lab scale) Ibuprofen Suspension (4 % = 400 mg/10 ml)..4 g Sucrose ......... I 1.......................................................................94 % (after 4 weeks) Redispersibility............................... sediment volume ........white Aspect ................100 % (after 1 day) Rel................................. Kollidon 90 F and sodium citrate in about 40 ml of water.............................................. Manufacturing Dissolve sucrose......................................Homogeneous Viscosity.........2 g Sodium citrate........ad 100 ml 2.5.............................. 3... Suspension properties Color ................2 g Water.... Formulation Ibuprofen (Knoll-Boots) ......... sediment volume .........................................................low Rel..........................very easy (after 4 weeks) BASF Fine Chemicals Generic Drug Formulations 1998 .......8 g Kollidon 90 F [1] .......

Relative sediment volume. 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 . 4 weeks [%] 4.

.........s................10............ BASF Fine Chemicals Generic Drug Formulations 1998 .. Water..................... II 1....q.........0 g Lutrol F 68 [1].......5.... Properties of the suspension The redispersibility of the suspension is very easy after 14 days at room temperature......................8 Liquid Formulations (Lab scale) Ibuprofen Suspension (4 % = 400 mg/10 ml)......81 g 2.0 g Cremophor RH 40 [1] .............. Ibuprofen (Knoll-Boots) ......0 g Preservative .... II.......... Manufacturing Dissolve Lutrol F 68 and the preservative in water II and ibuprofene in Cremophor RH 40 (I)..4................5..... The viscosity is low............ Formulation I............ 3........... Add the solution II slowly to the ibuprofeneCremophor RH 40 mixture I whilst stirring.................

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

4 % – 91% 120 N – 0. 10 min 20 min BASF Fine Chemicals Generic Drug Formulations 1998 – – – 85 % 87 % 8 Months 12 Months 121 N 2 – 3 min 0. 2 (20–25ºC) 6 Months Hardness Disintegration Friability Dissolution.4.2 % 89 % 88 % . Physical stability of formulation No.

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

.............0 Avicel PH 101 [5] .....2......20.........3....................................108 N Disintegration......................... Tablet properties Weight ..10 mm Form ...... Kollidon 30 [1] .................20.................... dry...1....................2 % Dissolution...0 Water.....52...........................0 III...........0 Lactose monohydrate [8] .............................2..0 Potato starch [3] ................biplanar Hardness ..... mix with III and press with medium compression force (17 kN)..........................................................................9 Tablet formulations (Lab Scale) Ibuprofen Tablets for Children (150 mg) 1......................... Formulation I...............................100 % 4..95 % 20 min.....................0 Croscarmelose [5] ...........18... BASF Fine Chemicals Generic Drug Formulations 1998 ...........0.............................. pass through a 0......150...... Manufacturing (Wet granulation) Granulate mixture I with solution II.................. Avicel PH 102 [5] .............................................0........0 Aerosil 200 [4] ................... Remark Croscarmelose could be substituted by Kollidon CL................290 mg Diameter .....................................8 mm sieve............................. Ibuprofen ....2 g g g g g g g g g g 2....... 10 min.76............................0 II.............................7 Magnesium stearate [2]...................11 min Friability..... 3...................

Cool to room temperature....... Manufacturing Dissolve indomethacin in Cremophor RH 40 at 60 – 70°C... Formulation Indomethacin ....6.............. Physical stability (4 weeks........................ 4......... I 1......... 40 °C) No change of appearance....... BASF Fine Chemicals Generic Drug Formulations 1998 ............................... 3.........7 Formulations of semi-solid drugs (Lab scale) Indomethacin Gel (1%).......................15 Water.............. Properties of the gel A clear soft gel was obtained...........1 Cremophor RH 40 [1].74 g g g g 2.....................10 Lutrol F 127 [1] .. add slowly the water (60 – 70°C) stirring well the mixture and dissolve Lutrol F 127.

.......0 g Propylene glycol Pharma [1] ...... Water . Lutrol F 127 [1].............. 1: No change during 1 year at room temperature... dissolve II well stirring about 30 minutes... BASF Fine Chemicals Generic Drug Formulations 1998 ... mix with III and cool......................... II 1.. Physical stability Formulation No...1.......0 g g g g g g 2.0 – 15..........0 g III..20............. Manufacturing Heat solution I to about 70°C................0 23...... 2: No change during 12 weeks at 40 °C......6............. 1 I................................0 g Ethanol 96 %.......20........38... 2 1...... 3.....7 Formulations of semi-solid drugs (Lab scale) Indomethacin Gel (1%)...... Formulation No.... It forms a clear yellow gel.............0 22...........0 g No...... 23 °C and 6 °C..0 39.........21................... Indomethacin .........– Lutrol E 400 [1] .... Formulations No.0 g II................

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

.....................4 Formulation of granules.... Manufacturing Mix the components for about 10 min and fill in hard gelatin capsules to obtain 160 mg indomethacin in each capsule..... Formulation Indomethacin .320 g Aerosil 200 [4] ... dry syrups and Iyophylisates (Lab scale) Indomethacin Powder for Hard Gelatin Capsules (160 mg) 1................. Indomethacin dissolved [%] 3........................160 g Kollidon CL [1]......4........... 2................... 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 ......................q.s..

..3 mg Water..............5.......7 Formulations of semi-solid drugs (Lab scale) Indomethacin Suppositories (50 mg) 1....8........................3.....................6....slightly yellowish BASF Fine Chemicals Generic Drug Formulations 1998 ...........3 mg Lutrol E 4000 [1] .................141. II....0 g 2.0 g Lutrol E 6000 [1] .......................................... Properties of the suppositories Weight: ............... 3.......................................6 g Colour:.....................................................0 g EDTA .. Formulation I............16.............. Manufacturing Prepare solution II... Indomethacin . mix with the melted mixture I and fill into the moulds of suppositories..............14..........1........0 g Butylhydroxytoluene ...............................

......................................................176 N Disintegration ............................... Tablet properties Weight ....... pass through a 0...3 min Friability...................303 mg Diameter ..8 mm sieve and press with medium compression force.........3 g g g g 2.2........... DC 1..................9 Tablet formulations (Lab Scale) Indomethacin Tablets (50 mg).. 3..............................................................................................................227 Kollidon CL [1] .2 % BASF Fine Chemicals Generic Drug Formulations 1998 ..............0...............50 Ludipress [1] ...........................biplanar Hardness ............................................ Manufacturing (Direct compression) Mix all components......................................20 Magnesium stearate [2] ........... Formulation Indomethacin .............8 mm Form ..............................

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

......................................0....................5 min Friability.............................................9 Tablet formulations (Lab Scale) Indomethacin Tablets (100 mg) 1.. Formulation Indomethacin ........................................................biplanar Hardness.......................................3 g 2.8 mm sieve and press with low compression force..................................100 g Ludipress [1] .................2.....4 % BASF Fine Chemicals Generic Drug Formulations 1998 . 3....12 mm Form ................................................................500 mg Diameter ............................................ Tablet properties Weight ...397 g Magnesium stearate [2] ........ Manufacturing (Direct compression) Mix all components... pass through a 0....61 N Disintegration ...........................

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

..5 g Lactose monohydrate [8] .......................... Formulation Isosorbide dinitrate + Lactose (4+6).............1% BASF Fine Chemicals Generic Drug Formulations 1998 ............................................. 3............4 g Kollidon CL [1] ....................0........9 Tablet formulations (Lab Scale) Isosorbide Dinitrate Tablets (5 mg) 1...0 g Magnesium stearate [2]...152.....................................9.2... Tablet properties Weight ................8 mm Form ........................................ Manufacturing (Direct compression) Mix all components..........12................................1 g Kollidon 30 [1] .....0 g 2............................................< 1 min Friability ...................8 mm sieve and press with low compression force........1............................biplanar Hardness........45 N Disintegration ..........................5...........184 mg Diameter .................... pass through a 0.......

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

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

............................... Mix and press with low compression force.......2........00 g g g g 2............... Manufacturing (Direct compression) Prepare premix I............................................................biplanar Hardness ........00 g Ludipress [1] ....6 mm Form ......05 g Citric acid....05 10......– Magnesium stearate ........0.........8 mm sieve...........05 mg) 1.......... The effectiveness was not controlled in this formulation.......00 1.............................. 2 Weight .. II.......... 2 is the stabilization of the active ingredient..................... 2 0............... Formulations No...........1% 4.00 89.........................9 Tablet formulations (Lab Scale) Levothyroxine Tablets (0.................. Tablet properties No.. add II and pass the mixture through a 0. Levothyroxine sodium .............103 mg Diameter ........... Remarks If the content uniformity of formulation No..... The function of citric acid in formulation No...... 3..... BASF Fine Chemicals Generic Drug Formulations 1998 ....................00 g No.............1..0..................1 – 2 min Friability..................... 1 No........52 N Disintegration........not controlled 101 mg 6 mm biplanar 45 N 4 min < 0.............. 1 I....99........ anhydrous....................1% Content uniformity ....................... 1 does not meet the requirements it would be recommended to add a small part of Ludipress (= part II) to the premix I.....

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

................. BASF Fine Chemicals Generic Drug Formulations 1998 ................................... Formulation I... Lidocain hydrochloride.....15 II.... Liquid paraffin .......... Manufacturing Prepare solution I at room temperature and mix with II.10 III. 20–25°C) No change was observed...................50 Propylene glycol Pharma [1] ..... Heat to 70 °C or cool to 6 °C and add slowly III to the well stirred solution until it is dissolved...................5 Water...................... Maintain cool until the air bubbles escaped..7 Formulations of semi-solid drugs (Lab scale) Lidocain Gel-Cream (5 %) 1.20 g g g g g 2............................. 3..6. Physical stability (3 months................................ Lutrol F 127 [1] ..

....... Manufacturing (Direct compression) Pass all components through a 0.....................................2.2 % BASF Fine Chemicals Generic Drug Formulations 1998 ..10 g Ludipress [1] ....................................................................................................................... Formulation Lisinopril ...biplanar Hardness....................2 – 3 min Friability......1 g 2..0................8 mm sieve.............9 Tablet formulations (Lab Scale) Lisinopril Tablets (10 mg) 1........ 3........................94 N Disintegration...........8 mm Form .......................................................................139 g Magnesium stearate [2] ................................... mix intensively and press with low compactation force (10 kN).............152 mg Diameter .............. Tablet properties Weight ....................

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

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

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

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

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 .Number of shakings needed to homogenize 4.

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

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

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

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

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

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

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

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

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

........650 mg Diameter .......................................... mix with III...> 200 N Disintegration ........100 g Kollidon 90 F [1] .........15 g II...............................................5 g Polyethylene glycol 6000..........2...................................................6 min Friability.............. Metformin hydrochloride ...................12 mm Form .... Manufacturing (Wet granulation) Granulate the mixture I with solution II.... Tablet properties Weight .........................3 % 4.................... Formulation I...9 Tablet formulations (Lab Scale) Metformin Tablets (500 mg) 1............ pass through a 0.....................................8 g Isopropanol.......................................biplanar Hardness ..................90 g III.... BASF Fine Chemicals Generic Drug Formulations 1998 ...........15 g 2................................................ Kollidon CL [1] .. Remark Due to the high hardness the amount of Kollidon 90 F could be reduced........8 mm sieve and press with medium compression force.............................. powder [6] .......................................... Kollidon 90 F [1] ...... 3.500 g Dicalcium phosphate [9]........0....

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

. 4...6 Propylene glycol Pharma [1] .................................... Lutrol F 127 [1] ... Methyl salicylate ..............5 Lutrol E 400 [1]...... Formulation I......20 Cremophor RH 40 [1] ..............................................6...... 3.................. Manufacturing Dissolve II in solution I and mix with III............... BASF Fine Chemicals Generic Drug Formulations 1998 .19 g g g g g g g 2......... The clear gel can be diluted with water......................... 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..................7 II.............................7 Formulations of semi-solid drugs (Lab scale) Methyl Salicylate + Menthol Gel (11% + 5 %) 1....................................... 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..............11 Menthol ...32 III.... Water..........

............ 20–25 ºC) Weight ................................100 % BASF Fine Chemicals Generic Drug Formulations 1998 .................................2................................................. pass through a 0.......... 3.8 mm sieve and press with medium compression force..89............................1% Dissolution (15 min) ...................0 g Ludipress [1] ..............10... Tablet properties Weight ...................6 mm Form ..........0........ Formulation Metoclopramide hydrochloride ................100 mg Diameter ..............0.................................................5 g Magnesium stearate [2]..biplanar Hardness...35 N Disintegration (gastric juice) .5 g 2........................... Physical stability (18 months.................100 mg Hardness...............1% Dissolution (15 min) ..35 N Disintegration (gastric juice) .100 % 4.................. Manufacturing (Direct compression) Mix all components.....3 min Friability ..........................................................................................0.........................................................3 min Friability ...9 Tablet formulations (Lab Scale) Metoclopramide Tablets (10 mg) 1....................................................

............................................50 g 2..... mix with III and press.........................................150 ml III............... Tartaric acid.........................4 min Friability...............1........biplanar Hardness ...........30 g II. Formulation I.............................................................................500 g Sodium bicarbonate ................................................113 N Disintegration ......10 g Isopropanol ...................9 Tablet formulations (Lab Scale) Metronidazole Effervescent Vaginal Tablets (500 mg) 1.................8 % BASF Fine Chemicals Generic Drug Formulations 1998 ......... Tablet properties Weight.....................1700 mg Diameter ............................................ Kollidon 30 [1] ..............2.... Manufacturing (Wet granulation) Granulate I with solution II....................8 mm sieve.. Metronidazole ......16 mm Form ..........................600 g Kollidon 30 [1] ............... powder [6]............. pass through a 0.500 g Polyethylene glycol 6000.. crystalline............................ 3.....

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

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

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

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

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

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

.....................3...1300 mg Diameter ....................... 2 Weight ........................................biplanar Hardness ...................................................1% 4......1% 1205 mg 16 mm biplanar 88 N < 1 min < 0.............................................< 1 min Friability .................... 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................... BASF Fine Chemicals Generic Drug Formulations 1998 C 95 % 94 % ........................................16 mm Form . 1 No........................... Chemical stability of formulation No........ Tablet properties No.. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application..94 N Disintegration (water).......

................2 g Nicotinamide .000 i.......... Formulation Vitamin A acetate dry powder.....0 g Kollidon VA 64 [1] ........./g (BASF) Thiamine mononitrate (BASF) .2.7..............0 g 500....................0 g Vitamin D 3 acetate dry powder 100..........0 g Raspberry flavour.3............. dry powder ..............8 g Cyanocobalamin 0.... dry powde ..........200.................. u..................200..... BASF Fine Chemicals Generic Drug Formulations 1998 ................5 g (BASF) Ascorbic acid................0 g Orange flavour...........000 i.......................1......6..0 g Pyridoxine hydrochloride (BASF)..........0 g dry powder SD 50 (BASF) Sorbitol.......60.......1......2........ dry powder..... pass through a 0. crystalline [10] ....0 g 2.................. Manufacturing (Direct compression) Mix all ingredients.....20................ u....9 Tablet formulations (Lab Scale) Multivitamin Chewable Tablets for Children 1............................2 g Riboflavin (BASF)./g (BASF) ...8 mm sieve and press with medium to high compression force (20 kN).1..................1% dry powder .30......0 g Aerosil 200 [4] ..............0 g Cyclamate sodium...........20.0 g Sucrose....6.......................0 g Passion fruit flavour. crystalline.5.... powder (BASF) ..........................31...........0 g Vitamin E acetate ..1..

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

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

......... dry syrups and Iyophylisates (Lab scale) Multivitamin Effervescent Granules (1 RDA of Vitamins) 1......00 g Cyclamate sodium ....00 g Saccharine sodium .00 g III... Fill 3 – 4 g in sachets........1........./g CWD (BASF) ...50 g Vitamin D 3 dry powder 100..20.00 g 2........0...............20. BASF Fine Chemicals Generic Drug Formulations 1998 .................... powder (BASF) ........0........ Manufacturing Granulate mixture I with solution II.... Thiamin hydrochloride (BASF).......... Formulation I.........80 g Vitamin E acetate dry powder 50 %.................000 I..U..35.0...........00 g Isopropanol ..............1.......00 g Citric acid .....0.........................................0......10 g II.....10 g Pyridoxine hydrochloride (BASF)......15............4 Formulation of granules...............U...........40......00 g Flavours .......................................................00 g Fructose ............8 mm sieve..... Kollidon VA 64 [1] ........25...............10 g Cyanocobalamin gelatin ..1% (BASF) Sodium bicarbonate ...........................................66 g coated 0....2.....00 g Sucrose .........../g CWD (BASF) ............50...........1.....0...............................4...25 g Calcium D-pantothenate (BASF) ................130..........26 g Riboflavin (BASF) .............00 g Kollidon CL-M [1]................... dry well and mix with III.. Vitamin A acetate dry powder 325........2......... pass through a 0....................000 I.....................80............30 g Nicotinamide .......50 g Ascorbic acid...

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 . 4. Properties of the granules Colour: Flowability: Dispersibility: Yellow granules Very good 4 g disperse homogeneously in water after about 40 seconds.

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

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

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

...........................Disintegration (water) ......1 – 2 min Friability............. 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 ...........1% 4..........................

...5 g Pyridoxine hydrochloride (BASF) ..500...............30.0 g Fructose .........................0 g Vitamin E acetate dry powder 50 % ............0 g Sodium bicarbonate ..........0 g Cyanocobalamin 0.400..0 g 0.............0 g Flavours (Firmenich) ..................................... Manufacturing (Direct compression) Mix all components.. crystalline ................. sieve through a 0.........................200...– Tartaric acid.....20...................5..............0 g 100...................8 mm screen and press with high compression force at maximum 30 % relative atmospheric humidity.0 g 200.....................6.110..................... Formulations No..................600.................0 g 30............ powder [6]....... powder ........0 g Polyethylene glycol 6000........5..0 g Ascorbic acid.1% dry powder ...0 g 20.. 1 No.......200.......0 g Vitamin A palmitate dry powder 325000 i...............5 g 60...................2..0 g Sucrose....0 g Saccharin sodium ..5 g Cyclamate sodium.0 g Ludipress [1] ..200....5 g 40.0 g 2............. BASF Fine Chemicals Generic Drug Formulations 1998 .....0 g – 500.30.....5 g Nicotinamide ....................9 Tablet formulations (Lab Scale) Multivitamin Effervescent Tablets II (3 – 4 RDA of Vitamins) 1...... 2 Thiamine mononitrate (BASF) .60..5 g Ribolfavin (BASF).....................0 g Citric acid..70.... u...0 g 500..........0 g 50............5 g 5.0 g 500.... powder ..40...........0 g 30...100.......0 g 70.......5 g 6...0 g 5..0...............0 g 200......./g CWD (BASF) ........ powder (BASF).0 g 200............................0 g Calcium D-pantothenate (BASF)...

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

.........................0 g II........................................s..............0......... i............ Preservative ..4.. Formulations No.........q..............1 g 0..................0 g Solutol HS 15 [1] ...........27 mg 40 Mio........1 g Pyridoxine hydrochloride../g (BASF) Vitamin D 3 (Cholecaciferol) ....0 g 22..1 g 0...ad 10 ml 4..........................5 g Benzyl alcohol........5 g 2..........5 g 2.......5 Mio..8 Liquid Formulations (Lab scale) Multivitamin Injectable for Veterinary Application 1..1 g Thiamine hydrochloride.... BASF Fine Chemicals Generic Drug Formulations 1998 .................100 ml 100 ml I...6 g Riboflavin phosphate sodium ......0 g q./g Vitamin E acetate (BASF) ......5 g 1................ u..1..........10 mg Water .... Nicotinamide .........1..6 g 10 mg ad 10 ml Total amount......... Water for injectables ............... Prepare solution III and add to the cool mixture I/II................6 g EDTA sodium ....................................... 2 Solution Vitamin A propionate ................ stir well and add very slowly the hot solution II... Manufacturing Heat mixture I to about 65 °C...................0.............s....................... 27 mg 2...... u...................0................................................ 1 Emulsion No..........1 g Butylhydroxytoluene ....5 g Dexpanthenol.6 g 0.................2.............................0.............................1 g 0....................0.ad 90 ml III.6....... ad 90 ml 1........5.......... i......5 g 0......

3. Properties Emulsion (formulation No. 1) A yellow milky emulsion was obtained having a viscosity below 5 mPa · s and a pH of 4. Solution (formulation No.5. 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 4.1.

.000 g Ethanol or Isopropanol ...................1...... Vitamin A+D dry powder 250....... Manufacturing Pass mixture through a 0............... 3....110 g Pyridoxine hydrochloride (BASF).................approx...22 g Calcium D-pantothenate (BASF) ........ II.......150 g Vitamin E acetate dry powder ... E and B 12 should be added after the granulation of the other components......33 g Nicotinamide .........26 g Riboflavin (BASF)............ BASF Fine Chemicals Generic Drug Formulations 1998 ............1....000 + 50....000 g Orange flavour...................................4 Formulation of granules..000 g Kollidon CL-M [1]..............................8 mm sieve and granulate with solution II in the fluidized bed................. finely ground ..5./g CWD (BASF) ...........000 g Kollidon VA 64 [1] .........U..1%.........................4......2.000 I........ dry syrups and Iyophylisates (Lab scale) Multivitamin Instant Granules (2 – 4 RDA of Vitamins) 1.....200 g Thiamine mononitrate (BASF) ..20.........210 g SD 50 (BASF) Sucrose........... Administration Suspend 6 –12 g (= 1 sachet) in a glass of water corresponding to 2 – 4 RDA of vitamins... the dry powders of vitamin A.. If the technology of a fluidized bed is not available..................... 7 l 2.........150 g Cyanocobalamin 0......... Fill 6 –12 g of the granules in sachets............. Formulation I.................66 g gelatin coated (BASF) Ascorbic acid powder (BASF) ...........

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

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

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

.. Properties A clear yellow gel was obtained..................0 ml Vitamin A palmitate ......................................55..........20......7 Mio....5... Dissolve at 20 – 25 °C the components III in this clear solution I/II.............14.50 mg Ascorbic acid....150 µg Cremophor RH 40 [1]...0 g IV....0 g Lutrol F 127 [1] .......................................u...0 g I...7 Formulations of semi-solid drugs (Lab scale) Multivitamin Oral Gel with Linoleic Acid and Linolenic Acid 1..... Thiamine hydrochloride (BASF) ........................ Water........................ Add the warm water II (65 °C) slowly to the well stirred mixture I... Maintain the cool temperature until the air bubbles escaped......u... Formulation Evening Primrose Oil (Epopure®.....6....................................3 mg Riboflavin (BASF) .. crystalline (BASF) .............10 mg Nicotinamide . Total amount: .......15 mg Cyanocobalamin........... Prima Rosa/SA) ............0 g III................0 g II..................5...30 mg 1...10 µg Calcium D-pantothenate (BASF) ... Manufacturing Prepare mixture I and heat to about 65 °C............. 3................ Lutrol F 127 [1] ................................./g ................. BASF Fine Chemicals Generic Drug Formulations 1998 ......19 mg Vitamin D 3 40 Mio i....../g (BASF) Vitamin E acetate (BASF)...3 mg Pyridoxin hydrochloride (BASF) ...about 100 g 2.......... Cool the obtained solution to about 5 °C and dissolve the rest of Lutrol F 127 (= IV).. i.... crystalline ...............1.....................................

BASF Fine Chemicals Generic Drug Formulations 1998 . Remark 5 ml of Evening Primrose Oil Epopure contains 3.4.45 g gamma-linolenic acid.5 g linoleic acid and 0.

....0 mg Nicotinamide ............. Formulation I......6 g Water........0 – 4..........15........0 g V...... Glycerol ..... III/IV and V and adjust the pH value to 4....... crystalline (BASF).....................................0 mg Propylene glycol Pharma [1] .........15...............................0 g Total amount .......0 mg Butylhydroxytoluene .............. Manufacturing Heat I and II separately to about 60 °C and mix slowly well stirring to obtain a clear solution.....25........... i...................5....0 mg Riboflavin 5’-phosphate sodium.0 mg IV...................15........0 mg Ascorbic acid.......u...55......100..........0 mg Citric acid.................2..................0 mg Pyridoxine hydrochloride (BASF) .. BASF Fine Chemicals Generic Drug Formulations 1998 .....0 g III..80.0 g Methyl parabene ..................7 Mio....... i./g. u............4.....300.. Saccharose .......10......../g (BASF) . Dissolve III in the hot solution IV to obtain a clear solution........................10..........0 mg Sorbic acid ..0 mg Cremophor RH 40 [1] .....................05 mg Vitamin E acetate (BASF) ........ Thiamine hydrochloride (BASF) ....................................8 Liquid Formulations (Lab scale) Multivitamin Syrup.............................100 g 2............100............200......0 mg 1......................................................... Vitamin A palmitate ..........5 g II.............9.. Vitamin D 40 Mio.......................... Mix the cool solutions I/II.............5...0..... I (1 – 2 RDA/20 ml) 1..... Pass during 10 min nitrogen through the solution and fill in flasks under nitrogen....2.45............. Water .....

3. Chemical stability (20–25 °C. 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 % .

....... Manufacturing Heat mixture I to about 65 °C.. Thiamine hydrochloride (BASF) ..........................05 g Riboflavin phosphate sodium .............. 3...3.... Mix with solution III and add the syrup IV........................ yellow viscous liquid.........0.......................00 g III..25 g Water .......0..5 g IV.02 g Pyridoxine hydrochloride (BASF).. BASF Fine Chemicals Generic Drug Formulations 1998 ..............0.0.....ad 100 ml 2. stir well and add very slowly the warm solution II (65 °C).....17.....00 g II....0...........10 g Water ...5..1...0....... II 1......1 mg Butylhydroxytoluene .......... crystalline (BASF) ....u.................0 mg Cremophor RH 40 [1]..0 mg 1........ Physical stability (20–25 °C protected from light) No change of the appearance after 3 months............ Parabenes .... 4...................17.7 Mio i..... Vitamin A palmitate ................................................ u.../g (BASF) Vitamin D 3 40 Mio i...8 Liquid Formulations (Lab scale) Multivitamin Syrup.................... Sugar syrup USP. Properties of the syrup Clear...............................02 g Ascorbic acid.../g ... Formulation I......

.........9 Tablet formulations (Lab Scale) Multivitamin Tablets I (1 – 2 RDA of Vitamins) 1.........5 g Pyridoxine hydrochloride (BASF) .2 g Cyanocobalamin 0......................2 g Ribolfavin (BASF)........................0 g 2..... 2 Vitamin A acetate dry powder ...............................7.2 2...0 g Orange flavour .....85...........................0 g Microcrystalline cellulose....2 g Saccharin sodium . Manufacturing (Direct compression) Mix all components......0 g Vitamin E acetate dry powder SD 50 .....0 g (BASF) Ludipress [1] ..........1% dry powder.2..16...........2 g 16....2..........0 3.............. powder (BASF)............– Magnesium stearate [2] ....2....5 g 11.....5 g 10.......5 g Calcium D-pantothenate (BASF) ........................2 g Nicotinamide . pass through a 0...2.6.... 1 No...... Thiamine mononitrate (BASF) .....................0 g 500...... u...– (Rettenmaier) Kollidon VA 64 [1]..........000 i...............2 g 2. BASF Fine Chemicals Generic Drug Formulations 1998 ...............11....... Vitacel ® ...5 g g g g 2..10..3.......0 g 31....8 mm sieve....................................31... mix and press with medium compression force (15 kN)......................321.......0 g Ascorbic acid......5 g 2..0 g 85....0 g – 300...2...........................0 7...... Formulation No..../g (BASF) .2 g 6........................0 g 21...............................

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

20......0 Orange flavour.0 Avicel PH 101 [5] ... Thiamine hydrochloride (BASF) ......................................0 Pyridoxine hydrochloride (BASF)........................11...........20.........2............300......0 Cyanocobalamin gelatin coated 0............1% (BASF) .................................000 + 50........0 Ascorbic acid.... Kollidon 30 [1] or Kollidon VA 64 [1] .............................6.......... Tablet properties Weight .....................................0 Nicotinamide ./g (BASF).................560 mg Diameter .7.............................0 II. crystalline (BASF) ................. u.......................12 mm Form .......................................1% BASF Fine Chemicals Generic Drug Formulations 1998 .......2 Mannitol ..................................................... Vitamin A acetate + Vitamin D 3 dry powder 500................................................ Formulation I...............< 0.............................2................. 80 III....................000 i.. mix with the components III and press with medium compression force............................2............................................................. dry..................100 N Disintegration (water)........................................................80................9 Tablet formulations (Lab Scale) Multivitamin Tablets II (1 – 2 RDA of Vitamins) 1..................................ca..................8 mm sieve............................2 Riboflavin (BASF) ...................................................................................................... Manufacturing (Wet granulation) Granulate mixture I with solution II.........................biplanar Hardness.......0 Isopropanol .0 Saccharin sodium...........65.............................................................................. pass through a 0.....0 Vitamin E acetate dry powder SD 50 (BASF) ........2 Calcium D-pantothenate (BASF) .3..........2.............................2.............................0 g g g g g g g g g g g g g g g g 2...........31..................11..0 Magnesium stearate [2]................................................................................................. 3...1 – 2 min Friability ..

500 i.4. u.500 i. u./g = 92 % Vitamin C 85 mg = 106 % 82 mg = 102 % 77 mg = 96 % BASF Fine Chemicals Generic Drug Formulations 1998 ./g = 100 % 14. closed) 0 Months 3 Months 6 Months Vitamin A 15. Chemical stability of vitamins A and C (20–25°C. u.300 i./g = 100 % 15.

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

.27 % 500.11..../g ........4..76 % Vitamin E acetate dry powder 50 DC............1...20 % Vitamin D 3 dry powder 100...38......09 % Ascorbic acid.........................40 % Phytomenadione dry powder 5 % GFP...........11.............50 % Thiamine mononitrate...................000 i.................. Remark The used vitamin mixture had the following composition: Vitamin A acetate dry powder .0.1...........................28...0........1...........................91% Folic acid ..96 % Nicotinamide..........000 i............1................ u........................................19 % BASF Fine Chemicals Generic Drug Formulations 1998 ....50 % Calcium D-pantothenate ........91% Pyridoxine hydrochloride .....86 % D-Biotin.................24 % Riboflavin ..1......0... u.......0................................................ 1% trituration .............15 % Cyanocobalamin gelatin coated 1% .......2.........../g Beta carotene dry powder BetaVit 10 % ..

.............7 min Friability .....................0.....20.......4..................................................000 i.0.........................2...........biplanar Hardness...../g (BASF) Thiamine mononitrate (BASF) ..... 3..........................0 % BASF Fine Chemicals Generic Drug Formulations 1998 ......................................0 g 500..........196...000 + 50......1........0 g Vitamin E acetate dry powder SD 50 ...0 g 2...........................5 g Riboflavin (BASF).........5. Manufacturing (Direct compression) Pass all components through a 0............................5 g Cyanocobalamin gelatin coated 1% ...8 mm sieve.............05 g Choline bitartrate .250 mg Diameter ...0......0 g Pyridoxine hydrochloride (BASF)...........................................0................... mix and press with low compression force..............................0..0 g Calcium D-pantothenate (BASF)....... Formulation Vitamin A + D 3 dry powder ...................20..........................0 g (BASF) Ludipress [1] .....................5 g (BASF) Folic acid .......2.. Tablet properties Weight ......9 Tablet formulations (Lab Scale) Multivitamin Tablets for Dogs 1.....................................................7 g Nicotinamide ......8 mm Form ......0 g Magnesium stearate [2].......... u.....77 N Disintegration (water) ..........................................

................. powder (BASF)..0 g (BASF) Ludipress [1] ................................ BASF Fine Chemicals Generic Drug Formulations 1998 . Manufacturing (Direct compression) Mix all components....– Magnesium stearate [2] .0 g Orange flavour ..0 g Vitamin E acetate dry powder SD 50 ..0 7...7............2 g 6.8 mm sieve...0 g Ascorbic acid................ 2 Beta Carotene dry powder 10 % Betavit ® ...........................0 g Nicotinamide ..............0 g (BASF) .. Beta Carotene dry powder 10 % ...2.................2....0 g 210.....0 g 85...........6............16.........2....0 g Saccharin sodium . pass through a 0...........................31..5 g 11.0 g 2....85..........0 g Riboflavin (BASF)..............0 g Kollidon VA 64 [1]...3......0 g Cyanocobalamin 0..............10.. Formulations No....0 g Pyridoxine hydrochloride (BASF) ........2..9 Tablet formulations (Lab Scale) Multivitamin Tablets with Beta Carotene (1 – 2 RDA of Vitamins) 1................– Pharma (BASF) Thiamine mononitrate (BASF) ................ 1 No......11.....................0 g 32.....321.............................2 g 2....2........... mix and press with medium compression force......................5 g 2...........0 3...1% dry powder...........5 g g g g g 2........................0 g – 70...................0 2..0 7...........................................0 g Calcium D-pantothenate (BASF) .....2 g 6....

............................. 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..1% 449 mg 12 mm biplanar 47 N 10 min 0.... BASF Fine Chemicals Generic Drug Formulations 1998 .......< 0.......508 mg ..............................................15 % 4.........biplanar ........... Remark Formulation No....... 2 ......................3....... Tablet properties Weight Diameter Form Hardness Disintegration Friability No.......................... 1 No.......12 mm ...........72 N (water) ............... 1 (20–25°C.......................... 1 could be commercialized in Europe as dietary food because all components are allowed for this application.... Chemical stability of vitamins in formulation No..5 min ......................

...................2............u............................. i.............6 mg Butylhydroxyanisol ............... solution 1 molar .........5........ Chamber 2: Dissolve the mixture I in the buffer solution II....... Vitamin A palmitate ..... keep it during 5 min under nitrogen bubbles...............................................70.................... pass nitrogen through the solution and fill in ampules under nitrogen..........252 mg Sodium hydroxide.............. Thiamine hydrochloride (BASF) ........................0............ Water.8.... BASF Fine Chemicals Generic Drug Formulations 1998 ..................... filter through a 0.....4 mg Solutol HS 15 [1] .......2 µm membrane and fill in ampules under nitrogen.. Formulations Chamber 1: I.............30.../g (BASF) Vitamin E acetate (BASF).................8 mg Propylene glycol Pharma [1] .....1..................................2 g Dexpanthenol (BASF) ... add slowly the water of the same temperature and mix with solution III...... Sodium ascorbate crystalline . i..........110 mg Riboflavin phosphate sodium...................0 g II..40 mg 1.................300 mg Folic acid ..9............2............ Adjust the pH to about 7.0 g Lutrol E 400 [1].................6 ml 2................. The pH-value is about 4....../g ....18 mg Citric acid... Sterilize at 120 °C during 10 min.............. Manufacturing Chamber 1: Heat mixture I to 60 °C.......................... Parabenes .......2.............. 0..................8 Liquid Formulations (Lab scale) Multivitamin Two Chamber Ampules 1............66 mg Nicotinamide ...............44 mg II.........u.......1 molar ..............2.4 ml Hydrochloric acid.......0 ml Chamber 2: I.....7 Mio.4...0.....0 ml Water for injectables .......2 mg Butylhydroxytoluene .0 g III.440 mg Pyridoxine hydrochloride (BASF) ......200 mg Vitamin D 2 40 Mio....

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

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

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

.....................2...................................0 g Water .............. 1 No..................5 g Kollidon CL [1]. 2 Naproxen (Syntex) ......................5 g – 25................2.. pass through a 0............ Kollidon 30 [1] ..– 457.......5 g Kollidon CL [1] ...... Manufacturing (Wet granulation) Granulate mixture I with solution II.. 2 Weight ........2 % 511 mg 12 mm biplanar 95 N 3 min 0........................ add III and press to tablets with low compression force...9 Tablet formulations (Lab Scale) Naproxen Tablets (450 mg) 1......................9 % 94....3 % Dissolution.. 1 No...........0 g 2............ Tablet properties No.... 2....12 mm Form ........................................25.........4 (10 min) ............................ 3.....biplanar Hardness..................................................95..90..457.......0.. pH 7...4 min Friability ..0 g III..........10.5 % (30 min)...................................................0 g I................................................ Magnesium stearate (Merck) .............................100 N Disintegration ......................496 mg Diameter ..3 % BASF Fine Chemicals Generic Drug Formulations 1998 .......................0 g 90....5 g 10.....85........3 % 86.... Formulations No.......................8 mm sieve.................0 g II..............

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

....250 Ludipress [1] .....10 g g g g 2........ Formulation Neomycin sulfate .............................................................................. Manufacturing (Direct compression) Mix all componnents.......................6 Aerosil 200 [4] ....8 mm-sieve and press to tablets with low compression force................. 3...................9 Tablet formulations (Lab Scale) Neomycin Tablets (250 mg) 1.12 mm Form ........................................76 N Disintegration...........................................2..........14 min Friability..... Tablet properties Weight ......................... pass through a 0...................8 % BASF Fine Chemicals Generic Drug Formulations 1998 ..................................................600 mg Diameter .0...334 Magnesium stearate [2] .....................biplanar Hardness............................................................................

..............biplanar Hardness................................................................419 mg Diameter ...............................5 mm sieve.... powder [6]................. mix and press with very low compression force...........200............................... 3.............................2..9 Tablet formulations (Lab Scale) Nicotinic Acid (= Niacin) Tablets (200 mg) 1.......... Manufacturing (Direct compression) Pass all componts through a 0...................................1 min Friability ..........................................................12 mm Form ....5.10..200......................2 % BASF Fine Chemicals Generic Drug Formulations 1998 .......0 g Kollidon CL [1] ................................ Formulation Nicotinic acid (Lonza).5 g Aerosil 200 [4] .............................0 g Polyethylene glycol 6000................................................ Tablet properties Weight ..........0 g Magnesium stearate [2] .......................0........1.........144 N Disintegration .......................3.......0 g Ludipress [1] ................0 g 2.

.............................. add IV and press with low to medium compression force.Eur........20.........................0 III.....223 mg Diameter .....2.................4 g g g g g g g 2.................. Methylene chloride........ Magnesium stearate ....0 IV............. Patent 0078.about 10 min Friability ............8 mm Form ............................................................0 Corn starch [3] ............................1% Dissolution (20 min)..........25.......................................180................0 Kollidon 25 [1] .biconvex Hardness ...10................ dry the obtained coprecipitate..............................90 % BASF Fine Chemicals Generic Drug Formulations 1998 .... Manufacturing (Wet granulation) Dissolve mixture I in II............9 Tablet formulations (Lab Scale) Nifedipine Tablet Cores (10 mg) (According to Ph......................132 N Disintegration .............. 3.........0..........105. Nifedipine................................................< 0. 1982) 1...... sieve.............40.0 II.......... Tablet properties Weight ............................................430......0 Kollidon CL [1]............... Formulation I.......... Microcrystalline Cellulose [5].... Granulate mixture III with solution I/II.....

5 Magnesium stearate [2].............................................................. Manufacturing (Direct compression) Pass all components through a 0......0....................63 N Disintegration .........3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...........26..82 mg Diameter ......................................................... Tablet properties Weight .................< 1 min Friability.5 g g g g 2...................................53.................................................9 Tablet formulations (Lab Scale) Nitrendipine Tablets (25 mg) 1.....0 Kollidon CL [1] .........0...... Formulation Nitrendipine.......................6 mm Form ...........2........biplanar Hardness...................5 mm sieve............... mix and press with low compression force................. 3...............1.......................................0 Ludipress [1] .........................

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

.....1 – 2 min Friability.............................100 Ludipress [1] .........biplanar Hardness...............................2......... 3........................................9 Tablet formulations (Lab Scale) Nitrofurantoin Tablets (100 mg) 1. Formulation Nitrofurantoin ......8 mm sieve and press with low compression force.......200 Magnesium stearate [2] ..3 g g g g 2...5 % BASF Fine Chemicals Generic Drug Formulations 1998 .......2 Aerosil 200 [4] .... Manufacturing (Direct compression) Mix all components..................... Tablet properties Weight ...85 N Disintegration........................12 mm Form ...............................0............................................................................... pass through a 0....................................................................................307 mg Diameter .............................................................

.......... add the sorbitol...0..5 Kollidon 90 F [1] ................. cool to room temperature and dissolve the other components..........46.....0 (Karion ® F liquid.......clear solution Taste ............. Properties of the syrup Appearance ....0.......4 Parabenes (Nipa) .... Formulation DL-Norephedrine hydrochloride.................. BASF Fine Chemicals Generic Drug Formulations 1998 ................0 g g g g g g 2.........................0.....0 Sorbitol solution ..1 to 0............................ Manufacturing Dissolve the parabenes in the hot water..................3.1 Saccharin sodium.. Flavours should be added to adjust the required taste.....reasonable 4................ Remarks To prevent of discolouration of Kollidon in the solution during storage 0.............50..............8 Liquid Formulations (Lab scale) Norephedrine Syrup (40 mg/10 g) 1.5 % of cysteine could be added as antioxidant..... 3...... Merck) Water.........................5.......................................

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

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

.......... pass through a 0....................55................biplanar Hardness ................................................................6 % 339 mg 10 mm biplanar 66 N 9 min 0.......................................54 N Disintegration ...........................8 mm Form ................8 mm sieve and press with very low compression force..........3 % BASF Fine Chemicals Generic Drug Formulations 1998 .....0 Aerosil 200 [4] ....................1................. Formulations 50 mg Nystatin ................0.................. 3.... Tablet properties 50 mg 100 mg Weight ..0 220..10 min Friability ..... Manufacturing (Direct compression) Mix the components.....0 Ludipress [1]...................................1....2...............0 Magnesium stearate [2] ............175 mg Diameter ................3 g g g g 100 mg 110.0 2................................................................9 Tablet formulations (Lab Scale) Nystatin Tablets (50 mg and 100 mg) 1.................................110...0 2.......................5 g g g g 2..............

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

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

...............018.. Add the sodium formaldehyde sulfoxylate and stir until dissolved.... ad 100.3.. Heat the solution to 75 °C.........s.......8 Liquid Formulations (Lab scale) Oxytetracycline Sustained Release Injectable for Veterinary Application (2................... BASF) must be selected in accordance with the legislation of the corresponding country.. Formulation Oxytetracycline.......00 g Sodium formaldehyde sulfoxylate .....00 ml 2..44 g 2-Aminoethanol . 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.......5................ and dissolve the Kollidon 17 PF in the mixture.....0.... set to pH 8...5 with aminoethanol.........g. 3.....22.... BASF Fine Chemicals Generic Drug Formulations 1998 ......889 (1976) 1.................... Manufacturing Mix the water and the Soluphor P.00 g Kollidon 17 PF [1] ..........84 g Water of injectables..2 g/10 ml) (According to US-Patent 4. After the solution has cooled...40...... The reducing agent e..............1....... slowly stir in the oxytetracycline until a clear solution is obtained........q....... After the magnesium oxide has been suspended..........5.........65 g Magnesium oxide .. sodium formaldehyde sulfoxylate (Rongalite‚ C.92 g Soluphor P [1] .....

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

......... Formulation Pancreatin (Knoll) ............................................... Tablet properties Weight ..................10 Magnesium stearate [2] .................. Enteric coating See Chapter 3................ Manufacturing (Direct compression) Mix the components...........................355 mg Diameter .....76 N Disintegration ..........................< 0................................ BASF Fine Chemicals Generic Drug Formulations 1998 ........... 3......................................................2.....................................................8 mm sieve and press with low compression force...........1% 4..... pass through a 0...30 Ludipress [1] ....8 mm Form .......................9 Tablet formulations (Lab Scale) Pancreatin Tablet Cores (30 mg) 1........................308 Kollidon CL [1]..........biconvex Hardness...........2 g g g g 2.4 – 5 min Friability .........................................

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

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

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

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

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

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

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

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

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

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

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

.........50 Sorbitol instant (Merck) ......................... Properties of the granules The free flowing granules are very well dispersible in cold water....... fine powder ... BASF Fine Chemicals Generic Drug Formulations 1998 .............. II............44 g in sachets (= 500 mg Paracetamol)............50 g g g g g g g 2......50 Citric acid.......4........... dry syrups and Iyophylisates (Lab scale) Paracetamol (= Acetaminophen) Instant Granules (500 mg) 1... Fill 2.3 Kollidon 90 F [1] ......................4 Formulation of granules.. Properties of the suspended granules The taste of the suspension is only slightly bitter (2. 4.................. Manufacturing (Wet granulation) Granulate mixture I with solution II and dry............44 g in a glass water)........8 Ethanol 96 % . Formulation I...............130 Lutrol F 127 [1] ....... No sedimentation can be observed during some minutes............ Paracetamol...................................... 3...... powder ............................3 Sodium citrate....

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

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

....4.....0 Water...................31.......20............2 to 0.....2-Propylene glycol Pharma [1] ...5 % of cysteine could be added as antioxidant...... crystalline [10]....... To prevent of discolouration during storage 0.... Formulation Paracetamol (Merck).................8 Liquid Formulations (Lab scale) Paracetamol (= Acetaminophen) Syrup (5 % = 500 mg/10 g) 1..... 4...........0 Sorbitol........0 g g g g g g g g 2..............................................5.0.........5.....1 Kollidon 25 [1] ....................... propylene glycol and water................ BASF Fine Chemicals Generic Drug Formulations 1998 ........................ 3.........0 Glycerol .......0 Strawberry flavour .......... Properties of the syrup Clear solution of certain viscosity having only a slightly bitter taste.......5.0 1.0 Cyclamate sodium...... 5. The colour of the solution changed only a little during 3 months at 25 °C and 40 °C... 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....15........ Chemical stability (HPLC) No loss of paracetamol was found during 3 months at 40 °C.. Manufacturing Dissolve first Kollidon 25 and then the other solid components in the solvent mixture of glycerol...............20.....

...............8 Liquid Formulations (Lab scale) Paracetamol (= Acetaminophen) Syrup for Children (2..............6......5.......2.......0 g Orange flavour ...4..............5 g Kollidon 25 or Kollidon 30 [1] .. add paracetamol and cyclamate...... Properties of the syrup The obtained syrup is a viscous..................1 g Raspberry flavour ........................< 0.. Formulation Paracetamol...................5 % = 250 mg/10 ml) 1.......30.............. Manufacturing Dissolve Kollidon in water.................0 g Sodium cyclamate ....0.. BASF Fine Chemicals Generic Drug Formulations 1998 ... Dissolve the flavours and mix with glycerol......... crystalline ..............................2 g Water ........... clear sweet and only slightly bitter liquid.5 g 2.....57............... 3........ heat to 50 °C and stir to obtain a clear solution..........0 g Glycerol .........

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

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

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

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

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

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

................ 3....................5 g Kollidon CL-M [1] .. 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 ....................................................................8 g Kollidon 90 F [1] ...1 g Preservative .................s. Water...................86 g 2................. Formulation Phenytoin ............5........... Manufacturing Dissolve the preservative and Kollidon 90 F in water and suspend Kollidon CL-M and phenytoin.................q............8 Liquid Formulations (Lab scale) Phenytoin Oral Suspension (5 %) 1.............................

.......8 Aerosil 200 [4] .................12 mm Form ......89 % BASF Fine Chemicals Generic Drug Formulations 1998 ............................... Manufacturing (Direct compression) Mix all components................biplanar Hardness....................... 10 min.....235 Magnesium stearate [2]............................................................. 3..0....................................9 min Friability..............100 Ludipress [1] ............. Tablet properties Weight ..............................................2...........9 Tablet formulations (Lab Scale) Phenytoin Sodium Tablets (100 mg)................57 % 30 min .......10 Kollidon CL [1] ....... pass through a 0..8 mm sieve and press with low compression force.......346 mg Diameter ............................................................................82 N Disintegration .5 g g g g g 2.2 % Dissolution................... DC 1............................................................................................. Formulation Phenytoin sodium (Sigma) .........................................

.9 Tablet formulations (Lab Scale) Phenytoin Sodium Tablets (100 mg)......................................50 Sucrose......biplanar Hardness.............................. Kollidon 25 [1] ......................... crystalline ................................... Manufacturing (Wet granulation) Granulate mixture I with solution II......5 Magnesium stearate [2] .. Formulation I......... mix with III and press with high compression force..............2.3 min Friability....................100 Dicalcium phosphate [9] .................................................................................. Kollidon CL [1] ..................10 Isopropanol + Ethanol (1 + 1) ....................5 % BASF Fine Chemicals Generic Drug Formulations 1998 ............45 II..0...................... dry.209 mg Diameter ..... Tablet properties Weight ..... Phenytoin sodium ..8 mm sieve..........60 N Disintegration ............................................................................................8 mm Form .................. 3....30 III........................................2 g g g g g g g 2........... pass through a 0.............. WG 1.

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

.0 Triethanolamine.. Manufacturing First mode of preparation: Prepare the solution of piroxicam in propylene glycol and dexpanthenol at 70 – 80°C..........0 Water.. Maintain the cool temperature until the air bubbles escaped......... Remark The addition of ethanol is not essential because it reduces the viscosity. dexpanthenol and triethanolamine.. Properties of the gel A clear colourless gel was formed having a pH of about 8.... add the rest of the water.......5 % + 5.................. Stirr the highly viscous mixture............... add ethanol and Lutrol F 127..................0 Ethanol 96 % .5.............5...........about 0........... Add the ethanol....... BASF Fine Chemicals Generic Drug Formulations 1998 ......2-Propylene glycol Pharma [1] .0...... 4......... Cool the mixture of Lutrol F 127 and water to about 5 °C and mix with the piroxicam solution................4 Lutrol F 127 [1] ......0 %) 1...............0 Dexpanthenol (BASF)................ add 50 % of the hot water (70°C)............46...... Formulation Piroxicam (Sigma)....0 g g g g g g g 2...6. 3......25.......7 Formulations of semi-solid drugs (Lab scale) Piroxicam + Dexpanthenol Gel (0................ cool to room temperature when the air bubbles escaped and adjust the pH to about 8..23... Alternative mode of preparation: Dissolve piroxicam in propylene glycol. adjust the pH with triethanolamine to about 7.....5 1.......

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

1% 2........9 % Magnesium stearate [2] ................................ 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.....2.......... Manufacturing (Direct compression) Mix the components.99.....0.. 3.9 Tablet formulations (Lab Scale) Placebo Tablets 1....... Formulation Ludipress [1].....05 % 15 kN 110 N 2 – 3 min < 0...05 % BASF Fine Chemicals Generic Drug Formulations 1998 .

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

.....7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine + Lidocain Gel (10 %) 1.....2............ Maintain the cool temperature until the air bubbles escaped....... 3..........9 IV.................. Sodium hydroxide solution.000 mPa · s pH value (20 % in water) ........ Lutrol F 127 [1] ....... Manufacturing Dissolve the solids (I) in water (IV)..........s pH value (20 % in water) .51...............54........6.... Water ....1......15............. cool to about 6 °C......4..... dissolve Lutrol F 127 (II) and adjust the pH value with the sodium hydroxide solution (III)....1.........7... 1 molar .....61........5 % BASF Fine Chemicals Generic Drug Formulations 1998 .. 52 °C) Viscosity (Brookfield.4 Loss of available iodine.... Stability (14 days..000 mPa..... PVP-Iodine 30/06 (BASF) .... 23 °C) ...0 III..........20......7 4... 23 °C).................. Formulation I............................ Properties of the gels Viscosity (Brookfield..................................0 II...10.....................0 Sodium chloride ...1 g g g g g g 2......0 Lidocain hydrochloride...

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

.3 45.....15....................3 g Glycerol monostearate.. 2 Loss of available iodine ..0 g Paraffin (56 – 58 °C) .....48.29....... 3..... Manufacturing Heat mixture II to 75 – 80 °C and cool to about 50 °C well stirring.1 (Wilco)... Pass the blend four times through a three-roller mill and let dry over night at room temperature................ No.. Cut the bar in pieces on a Lab stamper... 2 PVP-Iodine 30/06 (BASF) ... Chemical stability (40 °C during 4 weeks) No......0 g Water........................................6.3 g Emcol ® 4400... Add solution I and let cool to room temperature continuously stirring..........10.9...........3 29........– Cetylstearyl alcohol ...................3 g 48.....2 – g g g g 2......7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Bar Soaps (5 %) 1.....................5 % BASF Fine Chemicals Generic Drug Formulations 1998 .0 g 48...... II.........................0 g Texapon ® K 12 (Henkel) ..........................0 g 15....1% 11... 1 No...19...........2 g 10...........45....... Formulations I...........................0 19........48........3 g Setacin ® F special paste (Zschimmer + Schwarz) ......... 1 No......

.ad 100 g 20...................20.10.....................3 g 10...... 3......– Cremophor NP 14 [1]................... Administration as preventive desinfectant Dilute about 3 ml of the concentrate with 1 l of water....... Manufacturing Dissolve the surfactant II in solution III and add slowly PVP-Iodine I...........0 g III........0 g – 7....3 g 4....................................0 g ad 100 g I.. 1 No.............4.. 2 PVP-Iodine 30/06 (BASF).................5...8 Liquid Formulations (Lab scale) Povidone-Iodine Concentrates for Broilers and Cattles (20 %) 1.5.... BASF Fine Chemicals Generic Drug Formulations 1998 ...3 g Ethanol 96 % ......... diluted .................... II... Properties of the solutions Brown transparent liquids having a pH of about 1. 2.............7.. Formulations No.0 g Texapon ® K 12 (Henkel) .................................................0 g 5............3 g Sulfuric acid....... 4........... Tartaric acid .0 g Water ......

36. 4.........10... 3...10..2 molar........ BASF Fine Chemicals Generic Drug Formulations 1998 ........5 1....1 Na 2HPO 4 solution 0.......0 Liquid paraffin...................0 Cremophor A 25 [1] .2.....5....10..0 Cetylstearyl alcohol.1 molar .......................24.......6........1 0........................2...................... Chemical stability pH Available iodine Loss of iodine After production After 14 days/52 °C 4...... Properties of the cream Brown cream having a pH of 4........... PVP-Iodine 30/06 (BASF) .............0 Glycerol . Formulation I..................9 Cremophor A 6 [1] ..................7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Cream (10 %) 1........0 Citric acid solution 0... Stir in the PVP-iodine dissolved in the buffer solutions (I)........0 g g g g g g g g 2..99 % 9.... II......09 % – 4.......2 % During this stress test at 52 °C the emulsion was separated into two phases.......... Manufacturing Prepare a basic cream from the emulsifying agents and the fatty substances (II).....5.....

................. Formulation I............ PVP-Iodine 30/06 M 10 (BASF) .....9 % 4.................................... Manufacturing (Direct compression) Dry the mixture II for 4 hours at 60 °C.............................2...........................5 g Diameter .............................. BASF Fine Chemicals Generic Drug Formulations 1998 .............................9 Tablet formulations (Lab Scale) Povidone-Iodine Effervescent Vaginal Tablets (350 mg) 1.............................................biplanar Hardness............................... mix with I and III and press to tablets............2 mg mg mg mg mg mg mg 2..............360 Sodium bicarbonate..0..........................450 Tartaric acid ..........19 Calcium arachinate [2] .....................20 mm Form ..............1.265 III............. Application The tablet is dissolved in water to obtain a vaginal douche solution...... Tablet properties Weight ..............2.......7 min Friability.............................. 3............................... II..........................360 Ludipress [1]........................ Talc [10] ..200 N Disintegration in water.....2 Aerosil 200 [4] ....................

...................... 52 °C) The content of available iodine dropped to 98 %.. Fill the aerosol cans with 90 parts of this solution and 10 parts of propane + butane (1+3)...............ad 100 g 2....0. BASF Fine Chemicals Generic Drug Formulations 1998 .......8 Liquid Formulations (Lab scale) Povidone-Iodine Foam Spray (10 %) 1................5.0 g Cremophor A 25 [1] .....10.... 3....01 g Water ........ Manufacturing Dissolve PVP-Iodine in the solution of Cremophor A 25 in water..... Chemical stability (14 days......... Formulation PVP-Iodine 30/06 (BASF) .............

...... Properties of the concentrate Brown transparent liquid............................. 3................9.0 Water........... BASF Fine Chemicals Generic Drug Formulations 1998 ...1...0 g g g g 2.80..0 Propylene glycol Pharma [1] ........8 Liquid Formulations (Lab scale) Povidone-Iodine Gargle Solution Concentrate (10 %) 1..10..........5................... Manufacturing Dissolve the PVP-Iodine in the solvent mixture............. Administration Dilute 10 ml of the concentrate with about 100 ml of water... Formulation PVP-Iodine 30/06 (BASF) ...................0 Ethanol 96 % ....... 4...

0 % – 113........... Cool to 5 – 8 °C and dissolve V.000 mPa · s 3......1 0...... Formulation I..... Lutrol F 127.. PVP-Iodine 30/06 (BASF) ..6.........7...000 mPa · s 3...5......... 0..0 Citric acid solution............ 3....10..........15..18.....0 g g g g g g g 2....................... Chemical stability (20–25 °C) pH Available iodine Loss of iodine Viscosity (Brookfield) 0 Months 3 Months 6 Months 3.1 molar .....0 III......... Lutrol F 127.1 Lutrol E 400 [1]...0 V.9 NA 2HPO 4 · 12H 2O solution.....0 IV.. mix with III and dissolve IV at about 20 °C........95 % 5% 122....000 mPa · s BASF Fine Chemicals Generic Drug Formulations 1998 ..... II. Liquid paraffin.......7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Gel-Cream (10 %) 1..... Manufacturing Dissolve I in solution II... 4. Properties Brown turib gel.35.................... Maintain cool until all air bubbles disappeared........99 % 1% 124.2 molar ..4 1......1 0............................10... 0............

.. Water... 3...– II....2 % 2......70.. 1 I.6 No....000 mPa · s 1.... Maintain cool until all air bubbles escaped.............6..0 % ....0 g Sodium chloride ...... Stability (14 days........................0 g III.. Sodium hydroxide solution............0 1..0 7.....000 mPa · s 2...... Properties of the gels No... Manufacturing Dissolve the solids (I) in water (IV).. cool to about 6 °C. 1 Viscosity (Brookfield........– IV...0 20...... Formulations No.............. 52 °C) Viscosity (Brookfield........20..7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Gels (10 %) 1.0 g No.....10.... 1 molar. Lutrol F 127 [1] ... 23 °C) pH value (20 % in water) Loss of available iodine BASF Fine Chemicals Generic Drug Formulations 1998 58.... 23 °C) pH value (20 % in water) No.........1 g g g g g 2.....2 4.....000 mPa · s 54. 2 61.9 61.... PVP-Iodine 30/06 (BASF) ...7 8.. dissolve Lutrol F 127 (II) and adjust the pH value with the sodium hydroxide solution (III)....000 mPa · s 45.....9 10..... 2 10. 1 No. 2 4....

..........................9 Lutrol E 4000 [1].................84.. 3...6 Water.............. Dolder...................6. Manufacturing Dissolve Lutrol E 4000 in the hot mixture of glycerol and water and add the glucose warmed to 60 – 80 °C.3..................... After production After 14 days/52 °C 0.. 4.......4 % Remark A similar formulation using sucrose instead of glucose is mentioned in the European Patent 0258761 (Kowa).287 % 1.... PVP-Iodine 30/06 (BASF) .... 3..2................4 Glycerol .6 g g g g g g 2... 5 – 7) 1................... Properties of the ointment Brown viscous and turbid paste........ Incorporate solution (I) in the obtained paste .....4..........6 Ethanol 96 % . Formulation I...... Asanger. BASF Fine Chemicals Generic Drug Formulations 1998 ......5 %) (According to R............ M....... Febr.. Chemical stability Available iodine Loss of iodine 5..7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Glucose Ointment (2...0.0................ APV-Pharmazie in der Praxis No...........................5 Glucose [1].. 1987.... II.......291% – 0........

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

.. Chemical Stability The obtained solutions showed no loss of iodine after the storage of 15 days at 60 °C...... Manufacturing Dissolve Kollidon VA 64 in the mixture of solvents and add slowly PVPIodine to the well stirred solution.....– 10........ 1 No....... 2 PVP-Iodine 30/06 ...75.....0 g n-Propanol.................................................0 g 15..0 g – 75.... Fill in aerosol cans with propellants like propane+butane or with manual valves.............0 g Kollidon VA 64 [1] ... Formulations No.......8 Liquid Formulations (Lab scale) Povidone-Iodine Liquid Spray (10 %) 1.................................0 g 2.......0 g Ethanol ..... BASF Fine Chemicals Generic Drug Formulations 1998 .............................10....... 3.15............5.

.................................0 Aspartame............0 Eucalyptol........... Tablett properties Weight ..........................................................100 N Disintegration in water .> 10 min Friability.......5............................................0 g g g g g g g g 2.................1..........8 mm sieve an d press with medium compression force................ Formulation PVP-Iodine 30/06 M 10 (BASF) ..................................biplanar Hardness ........ Manufacturing (Direct compression) Mix all components.0 Magnesium stearate [2]..8 mm Form ..............2............... crystalline ....150............. sodium .1.....4........0 – 5..................2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................... cryst......0 – 5................. pass through a 0.........176 mg Diameter ....0...... [10].0 Menthol............ crystalline ..........9 Tablet formulations (Lab Scale) Povidone-Iodine Lozenges (5 mg) 1...................... 3........4.0.0 Sorbitol................ potassium ...............1....................0 Saccharine..................1 Aerosil 200 [4] ............

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

.82 % 2.0 g g g g g g g 2......5...................15......... BASF Fine Chemicals Generic Drug Formulations 1998 .....7.................89 % 2................5 Water ............... PVP-Iodine 30/06 (BASF) ....91% – 6 Months 12 Months 0....8 Liquid Formulations (Lab scale) Povidone-Iodine Mouth Wash and Gargle Solution Concentrate (7... II.......0......0 Menthol .........2 Anise oil + eucalyptus oil...... 1+1 .............0 Ethanol 96 % ............................50. Properties of the concentrate Brown transparent liquid having a fresh odour............... Chemical stability (20–25 °C) 0 Months Available iodine Loss of iodine 0.. Manufacturing Dissolve PVP-Iodine and saccharin in water and mix with solution II. A brown liquid is obtained having a fresh taste...5 %) 1............... Administration Dilute 10 – 20 ml with a glass of water..2 % 0..0..... 3.0.....5 Saccharin sodium.....1 Lutrol E 400 [1] .............. 4........2 % 5....15.................... Formulation I......................

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

........00 Potassium iodide .......98..................15 % Loss of iodine ................................– Free iodine ........ Properties of the solutions Clear..... Manufacturing Dissolve PVP-Iodine slowly in the solution of the salts....0........... 3............1....................16 % 0% 2......................2 ppm BASF Fine Chemicals Generic Drug Formulations 1998 ....8 Liquid Formulations (Lab scale) Povidone-Iodine Ophthalmic Solution (1..0.....................................11 Water .....39 g g g g 2..........50 Potassium iodate .....3 Available iodine .5.................................6...............0......... brown liquid of low viscosity.................9 ppm 7.................................................... 4..........0 %) 1.....1............. Chemical stability (Stress test at 52 °C) Initial After 14 days pH...2 0................. Formulation PVP-Iodine 30/06 ...

.......25......................... PVP-Iodine 30/06 M 10 (BASF)... Isopropyle myristate ......22..........4 Formulation of granules............... III.......25...................0 g g g g g g 2..4.5 Dow Corning 344 Fluid (DOW) ...... Manufacturing Suspend PVP-Iodine and Maize-PO4-Aerosol (I) in the liquid mixture II and fill in aerosol cans with the propellants III....1. 1+3 .....0 II.....50.0 Maize PO 4 Aerosol (Hauser) . Propane + butane.............. dry syrups and Iyophylisates (Lab scale) Povidone-Iodine Powder Spray 1....................0 Pentane ............. BASF Fine Chemicals Generic Drug Formulations 1998 .10.. Formulation I............

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

......... Properties of the solutions Brown............3 g – 2............. Manufacturing Formulation No...10.......2 g 59........ add Texapon and slowly dissolve the PVP-Iodine... Adjust the pH with the sodium hydroxide solution to about 3.– Texapon ® K 12 (Henkel) ...– Sodium biphosphate solution 0.....85...1...2 g Tylose ® M 300 (Hoechst) .......... 2: Dissolve Tylose M 300 in the mixture of the citric acid and sodium biphosphate solutions...... Formulations No............ As soon as both are dissolved add slowly the PVP-Iodine to the well stirred solution.............0 g 0..................1 molar..0 g – – – 2..............0....................5. clear solutions having a certain viscosity and a pH of 3 – 4..8 Liquid Formulations (Lab scale) Povidone-Iodine Seamless Solutions (10 %) 1...2 molar.... 2 PVP-Iodine 30/06 (BASF) ..6 g 10..... 1 No......... 1: Dissolve Lutrol F 127 and than Natrosol in the water...................... 1 molar solution......................... BASF Fine Chemicals Generic Drug Formulations 1998 ...........– Citric acid solution 0......5 g 28.3... Formulation No..........................– Water ..5...............0 g Lutrol F 127 [1].0 g Natrosol® HR 250 (Hercules)..2 g Sodium hydroxide............ 3...........

......... Formulation PVP-Iodine 30/06 (BASF) .... Properties of the shampoo Brown..............25. 4......5 – 0......5 %) 1...... clear solution... 52 °C) the loss of available iodine was about 12 %............... After cooling incorporate Neutronyx.0 Natrosol® 250 HR (Hercules) .. 3...........0....................4.... Manufacturing Dissolve Super Amide and Natrosol in hot water (about 60 °C) and then dissolve PVP-Iodine...8 Liquid Formulations (Lab scale) Povidone-Iodine Shampoo (7.0 Super Amide ® L 9 (Onyx) ...5.............7..........7 Water .......... Chemical stability In the stress test (14 days....5 Neutronyx® S 60 (Onyx) . The viscosity can be changed by modification of the amount of Natrolsol 250 HR....... BASF Fine Chemicals Generic Drug Formulations 1998 .ad 100 g g g g g 2....

.......1....Clear brown gel.............. 23°C) .................31............ Properties of the gel Appearance...6.0 g Natrosol® HR 250 (Hercules) ........7 Formulations of semi-solid drugs (Lab scale) Povidone-Iodine Soft Gel (1%) 1..... Viscosity (Brookfield..2.. Manufacturing Dissolve PVP-Iodine and Natrosol HR 250 in the well stirred water.......500 mPa · s BASF Fine Chemicals Generic Drug Formulations 1998 ..... 3....5 g 2......................... Formulation PVP-Iodine 30/06 (BASF) ...5 g Water........96.......................

.......... 1 year) 0 Month Available iodine pH BASF Fine Chemicals Generic Drug Formulations 1998 100 % 4.................2 46...10......4 ....... I 1.........0 g Lutrol F 127 [1] ... 1 (20–25 °C.– Lutrol E 400 [1] ..1 96 % 4.2 molar solution.......4 g No.5....... 4.................8 Liquid Formulations (Lab scale) Povidone-Iodine Solution (10 %). 2 10... 1 PVP-Iodine 30/06 (BASF) .......5..0 g g g g g 2............5 43.....6 g Na 2HPO 4 · 12H 2O 0............................ 3...... Chemical stability of formulation No......– Citric acid 0..46..... Formulations No.......... Manufacturing Dissolve the PVP-Iodine (and Lutrol F 127) in the mixture of the buffer solutions (and Lutrol E 400).0 0...4 6 Months 12 Months 100 % 4...43.1 molar solution ......3 0. Properties of the solutions Brown clear solutions having a low viscosity and pH of about 4.

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 %

.............................63 N Disintegration ........5 Aerosil 200 [4] ...........0.......8 mm Form .................2.....................10 Kollidon CL [1] .......20 Lactose monohydrate [8]................................................................... Formulation Prednisolone ..........2 % BASF Fine Chemicals Generic Drug Formulations 1998 .............. Tablet properties Weight ......................................212 mg Diameter ................................................................................... pass through a 0.155 Kollidon VA 64 [1] ...................................biplanar Hardness....9 Tablet formulations (Lab Scale) Prednisolone Tablets (20 mg) 1.......................................8 mm sieve and press with low compression force.............................................................................8 Magnesium stearate [2] ..........2 g g g g g g 2........... Manufacturing (Direct compression) Mix all components............. 3..............< 1 min Friability............

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

.......................................................43 % 60 min.........70 ml III..............100 % BASF Fine Chemicals Generic Drug Formulations 1998 .....biplanar Hardness........9 Tablet formulations (Lab Scale) Probenecid Tablets (500 mg) 1.. 5 min .................. Probenecid ................9 min Friability..............8 mm sieve.674 mg Diameter .................................................0.........500 g Corn starch [3] .................................. Kollidon 30 [1] .......25 g Aerosil 200 [4] ..............130 g II............ Formulation I.......................................................... 3........ Manufacturing (Wet granulation) Granulate mixture I with solution II.............3 g 2.......3 % Dissolution........................ add III and press with low compression force............3 g Magnesium stearate [2] ..............2.......................................10 g Ethanol 96 % ..................................................................................................................12 mm Form ............ pass through a 0........54 N Disintegration ....................... Tablet properties Weight ............................................... Kollidon CL [1] ..................

............ Water of injectables ...... 3.........ad 100 ml 2.0.......... Remark To prevent of discolouration of the dissolved Kollidon during storage 0................4 g Carboxymethyl cellulose............................5........................30..0......15 g Sodium citrate.................. Manufacturing Suspend procain penicillin G in the well stirred solution II...........0.........5 % of cysteine could be added as antioxidant...........8 Liquid Formulations (Lab scale) Procain Penicillin Injectable Suspension (300 mg/ml) 1..................0 g Kollidon 17 PF [1] ...........q............................... Procain Penicillin G ..........2 to 0...........................homogeneous Redispersibility ........easy 4..s................... Properties of the suspension Aspect . BASF Fine Chemicals Generic Drug Formulations 1998 ........ II............. Formulation I...q...........s....57 g Antioxidant.... Preservative ...........................

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

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

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

..........................................98 g Water.................................... Isopropanol...........................................2 min.........60 g 2.....3...............Position 10 Outlet flap..... Manufacturing of the suspension Dissolve Ethocel and Kollidon VA 64 in isopropanol.......................................................20 g Talc..................................5 kg Inlet air temperature ......................................................... 3...... Kollidon VA 64 [1] .......................5 Coating formulations (Lab Scale) Protective Film Coating with Ethyl Cellulose + Kollidon VA 64 1.140 g Water..................... Pass this mixture through a colloid mill and add solution II....................38 °C Inlet flap ....................1 mg BASF Fine Chemicals Generic Drug Formulations 1998 ..40 °C Outlet air temperature .............................13 g Sicovit Colour lake [1] ................................. II.................. Formulation I........q.......... Coating procedure (Fludized bed) Tablet core loading ..........59 g Isopropanol ...................15 min... Final drying.............. Quantity of film forming agent/cm 2 ...................................................................5 g Sicovit Titanium dioxide [1] ...5 g Ethocel ® 20 (Dow) ...........Positon 4 Spraying pressure .................................. s... add the water and suspend the colorants and the talc..................3 bar Spraying time.....................................................

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

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

...............................................................50 Water ...............38 °C Spraying pressure ..000 g g g g g g g 2....................15 Sicovit Titanium dioxide [1] ...............5 Sicovit Iron oxide or Lake [1] ....3...........ad 1................................................................................0............45 °C Temperature at outlet........................3 sec Accela Cota 2499 (continuous spraying) Spray gun ...................................................5 sec Dry air ..................................5 Coating formulations (Lab Scale) Protective Film Coating with Kollidon VA 64 1............................$ 50 min BASF Fine Chemicals Generic Drug Formulations 1998 .........................Walther WAXV with 0......6 sec Pause....................... Formulation Kollidon VA 64 [1] ....................................................30 Talc [10] ...................................40 Glycerol .8-mm nozzle Temperature at inlet ....... 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 1-mm nozzle Spraying time ................3 sec Pause........2 bar Spraying time ...................................................................50 Lutrol E 6000 [1]....................................................................................

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

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

.....20 Sicovit Titanium dioxide [1].........185 Talc ....... talc and the lake and mix in the colloid mill..........5 Coating formulations (Lab Scale) Protective Film Coating with Shellac + Kollidon 30 1..................................65 Cetyl alcohol ................ Manufacturing of the coating suspension Dissolve shellac and sorbitane oleate in the warm solvent and then Kollidon and cetyl alcohol........... 3................3............50 Isopropanol or ethanol .................................................................177 Kollidon 25 or 30 [1] ....30 Sicovit Colour lake [1] ...................... Formulation Shellac .... Add titanium dioxide...............15 Sorbitane trioleate .......................458 g g g g g g g g 2............................ 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 .....................................

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

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

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

...................... pass through a 0......0.2 – 3 min Friability.305 mg Diameter ............ BASF Fine Chemicals Generic Drug Formulations 1998 ........ 3............................. 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.............9 Tablet formulations (Lab Scale) Ranitidine Tablet Cores (150 mg) 1................147 mg Magnesium stearate [2]..............3 mg 2....150 mg Ludipress [1]...............8 mm screen and press with low compression force........................................................................biconvex Hardness.......................................8 mm Form ...........5 % 4.......... Tablet properties Weight ...........................................2................61 N Disintegration ... Formulation Ranitidine ........

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

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

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

....0 g Kollidon CL [1] . milled < 100 µm .................2.............3 g g g g – 2.......................< 2 min Friability ............15.....................................................................0 g Ludipress [1] .........................................0 2..9 Tablet formulations (Lab Scale) Saccharin Tablets (15 mg) 1..........2..........– No.................... 2 15.. Formulations No..........................2 % BASF Fine Chemicals Generic Drug Formulations 1998 51 mg 5 mm biplanar 29 N < 2 min 0.........0....51 mg Diameter .................0........... Manufacturing (Direct compression) Mix all components...........0 g 2.2 % .....................biplanar Hardness ...............2......8 mm sieve and press with medium compression force.. powder [6] ..................................... pass through a 0...0 0.. 3.3 g Polyethylene glycol 6000...........5 mm Form ........... 1 Saccharin sodium (Roth) .........0 g Lutrol F 68 [1]........ Tablet properties Weight ...........0 31...........................................31..............33 N Disintegration (water) ......0 g Magnesium stearate [2] ..........................

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

.................8 mm Form .........................< 0....10 g Ludipress [1] ..................biplanar Hardness............................8 mm sieve............................................................ Tablet properties Weight ....................... Formulation Serratio peptidase ..............................................................................................2 g 2.2 % BASF Fine Chemicals Generic Drug Formulations 1998 ................... 3.....................................238 mg Diameter ....80 N Disintegration .................. mix intensively and press with low compactation force (6 kN)...............................9 Tablet formulations (Lab Scale) Serratio Peptidase Tablets (10 mg) 1.........3 – 4 min Friability .. Manufacturing (Direct compression) Pass all components through a 0......2....228 g Magnesium stearate [2] ....

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

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

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

...0 g Fructose (Merck) .........5.. 4.. 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.....10............ – Easily dispersible in cold water without any physical separation during 30 min. 3....................g............ Manufacturing Introduce solution II into the mixture I... Formulation Simethicone (Abil ® 200....50......0 g Cremophor RH 40 [1] .......................... dry syrups and Iyophylisates (Lab scale) Simethicone Instant Granules (60 mg and 120 mg) 1..0 g II.........40.. – 98 % coarser than 50 µm.. crystalline (Merck) ... Kollidon VA 64 [1] ........................................4 Formulation of granules. 1 to 2 g) in 100 ml of drinking water.... Sorbitol..... Properties of the granules – Free flowing white granules.....0 g Orange flavour (Dragoco) .......... Fill 1 or 2 g in sachets. Goldschmidt) .0 g Ethanol .........0 g III.....50.......50..............0... 2...... dry and pass through a 1 mm sieve.... Granulate the powder mixture III with the well stirred mixture I/II....... BASF Fine Chemicals Generic Drug Formulations 1998 ...3................4.0 g Kollidon CL-M [1]..5 g I.....

....1.5 % of cysteine could be added as antioxidant.... Manufacturing Dissolve sobrerol slowly in the well stirred solution of Kollidon 17 PF.. 3..............1 to 0............. Formulation Sobrerol....2 µm filter.0 ml 2.......8 Liquid Formulations (Lab scale) Sobrerol Injectable Solution (75 mg/5 ml) 1...........0 g Water for injectables.... The sterilisation can be done by filtration through a 0......................clear Viscosity............. BASF Fine Chemicals Generic Drug Formulations 1998 .... Remark Preservatives could be added if it is needed...very low 4.6.............. To prevent of discolouration of Kollidon in the solution during storage 0...........5 g Kollidon 17 PF [1] .......... Properties Appearance .........................................................100..............5..........

...................56..25 Dicalcium phosphate........ pass through a 0.50 g g g g g 2..... Formulation Sodium fluoride (Merck) .............................2................................8 mm sieve and press with high compression force........... DI-TAB [9] ...................25 Kollidon VA 64 [1] ............ 3..............144 N Disintegration ............20 Magnesium stearate [2]....... BASF Fine Chemicals Generic Drug Formulations 1998 ....................... 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..........55 Sorbitol.....0....................116 mg Diameter ....8 – 9 min Friability ...< 0........ Tablet properties Weight...............biplanar Hardness ...1% 4............6 mm Form ...........................2..0... Manufacturing (Direct compression) Mix all components....................................................................................9 Tablet formulations (Lab Scale) Sodium Fluoride Tablets (0........5 mg) 1..56................ crystalline [10] ..........

.......biplanar Hardness....5 mm Form ........... pass through a 0........76..........< 0............................................... Manufacturing (Direct compression) Mix all components......1...............78 mg Diameter .................................. 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...... BASF Fine Chemicals Generic Drug Formulations 1998 .....................1% 4..................... Tablet properties Weight ..................4 min Friability .............................4 g 2.................................82 N Disintegration .3 g Ludipress [1] .............7 g Magnesium stearate [2].................... Formulation Sodium fluoride (Merck) ...... 3....................0.3 mg) 1...8 mm sieve and press with low compression force................................9 Tablet formulations (Lab Scale) Sodium Fluoride Tablets (1...........

..................13 min Friability . Formulation Spironolactone ............................... pass through a sieve and press with medium compression force................. Manufacturing (Direct compression) Mix all components.........1% BASF Fine Chemicals Generic Drug Formulations 1998 ..................................0 g Ludipress [1]...................................................1.......................................................... Tablet properties Weight ......153 N Disintegration.............................2.175................................biplanar Hardness ............5 g 2..................9 Tablet formulations (Lab Scale) Spironolactone Tablets (25 mg) 1.197 mg Diameter .......................< 0......................................25. 3.......8 mm Form ..........0 g Magnesium stearate [2].........

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

...100 g Ethanol or isopropanol ........... The amount of 0..... Formulation Kollidon VA 64 [1] .. BASF Fine Chemicals Generic Drug Formulations 1998 ...3........ 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..........5 Coating formulations (Lab Scale) Subcoating for Core Protection 1.4 mg/cm 2 tablet surface is sufficient for a good subcoating protection............. Remark No plastisizer is needed in this formulation due to the plasticity of Kollidon VA 64..........900 g 2.... 3....

......... 3...........30 g Magnesium stearate [2] ...........3 g 2.90 N Disintegration .........70 g II.........................20 g Ethanol 95 % .......................................... Sucralfate ....................................................................... mix the dry granules with III and press with low compression force. Formulation I............0.....................20 g Corn starch [3] ......................... Kollidon 30 [1] ...........................2.........................3 – 4 min Friability.........660 mg Diameter ......500 g Sodium alginate .................... Kollidon CL [1] ......... Manufacturing (Wet granulation) Granulate mixture I with solution II........................................................................biplanar Hardness.....9 Tablet formulations (Lab Scale) Sucralfate + Sodium Alginate Tablets (500 mg + 20 mg) 1...................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ....................................80 ml III..............................12 mm Form .................................. pass through a sieve................................................. Tablet properties Weight ......

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

................................................. Manufacturing of the coating suspensions Dissolve Kollidon........– Sucrose .0 17. 2 continue with the same procedure until homogeneous coloured sugar coated tablets are obtained.....70 g Sicovit Colour lake or Pigment [1]..........650 g g g g g g g g g 2. 4..........3..........................6 10............. 1 by means of the manual sugar coating procedure during some hours.... Mix in a colloid mill..0 5......1.....8 g Carmelose sodium.......................... manual 1... 2 Coloured 16............ After changing to formulation No.... Formulations No...7 g Talc ...............3 g Sicovit Titanium dioxide [1] ...650 g No... Polysorbate or Cremophor and sucrose in the water and suspend the other components in this solution....3 115........................................3 3.. 3.................135 g Water...8 14.......3.....6 g Aerosil 200 [4] . Remark The polishing can be done by means of a solution of beeswax or polyethylene glycol 6000....14..... Application of the coating suspension Start with formulation No.0 g Polysorbate or Cremophor RH 40 [1] ...81.......................135 1............... BASF Fine Chemicals Generic Drug Formulations 1998 .. 1 White Kollidon 30 [1] ....................5 Coating formulations (Lab Scale) Sugar Coating.........7 81...................16....10...5.

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

........ 3.............................. Manufacturing Dissolve sodium hydroxide in water and suspend the active ingredients and Kollidon CL-M..................... The pH was 12...... Properties of the suspension A homogeneous white suspension was obtained..8 Liquid Formulations (Lab scale) Sulfadiazine + Trimethoprim Veterinary Concentrated Oral Suspension (40 % + 8 %) 1........................... BASF Fine Chemicals Generic Drug Formulations 1998 ............8 Sodium hydroxide .................................44 g g g g g 2.............. Formulation Sulphadiazine........................5.6 Kollidon CL-M [1] .................40 Trimethoprim.......2 Water.. It showed some sedimentation after 7 days but the redispersibility was very easy...............................

................................................. Manufacturing (Wet granulation) Granulate mixture I with solution II............93............................................... Kollidon CL [1].................... Kollidon 30 [1] ...........465................................................... 10 min.........23............2 g Calcium arachinate [2] .............< 0....................0.2 g 2....152 N Disintegration .............. Formulation I....0 g Water .................................89 % BASF Fine Chemicals Generic Drug Formulations 1998 .....................200.0 g III....................77 % 20 min ..............................................0................................87 % 30 min .............1% Dissolution.14....8 g Aerosil 200 [4] ........................ dry....12 mm Form .........2...........0 g II................................................602 mg Diameter ............. add mixture III and press with low compression force....1...biplanar Hardness .........4 g Talc [10] ..................................... pass through a 0....8 mm sieve.....9 Tablet formulations (Lab Scale) Sulfadiazine Tablets (450 mg) 1........................................... 3...........0 g Lactose monohydrate D 20 [8] ..... Tablet properties Weight ............3 min Friability ............. Sulfadiazin ..................................

. Formulation I......40 ml Propylene glycol Pharma [1] ..... s........ Remark To prevent of discolouration of Kollidon in the solution during storage 0............2 to 0. Physical stability (20–25 °C) No recrystallisation after some weeks........5 % of cysteine could be added as antioxidant................5........70 g Antioxidant.....5 g Ethanol 96 % ...........5 % = 250 mg/10 ml) 1....... Manufacturing Mix solution I slowly with solution II at 60 °C and cool.........8 Liquid Formulations (Lab scale) Sulfadimethoxine Veterinary Injectable Solution (2.........................................................q.................... s...........7 Viscosity........ Water for injectables ...........40 ml Kollidon 12 PF [1] . Properties of the solution Appearance .......q...... 5...... BASF Fine Chemicals Generic Drug Formulations 1998 ... II...........clear pH.................... ad 200 ml 2................very low 4.................. 3................................... Sulfadimethoxine..........................................................

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

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

.................... s............. II...2. Formulation I................................0 g Lutrol E 400 [1]..........q....... BASF Fine Chemicals Generic Drug Formulations 1998 . 4. Physical stability No change of the clarity after 2 weeks stored at 6 °C and at 20 – 25 °C...68..................0 g Preservative ................ Heat the solution II to the same temperature and mix slowly with solution I.... Water........... colourless solution of low viscosity was obtained........ Sulfadoxine ... Manufacturing Prepare solution I at 60 °C..........8 Liquid Formulations (Lab scale) Sulfadoxine Solution (2 % = 20 mg/ml) 1.....30. 3.0 g 2..5......... Properties of the solution A clear.......................

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

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

.0 g II.....................3.......... Sucrose .........................2 g 8. 2.......8.......– Water...................................................... 2 Colour:...... 1 No.....6 g – 5...0 g Lutrol F 127 or Lutrol F 68 [1].....very easy beige very low very few easy BASF Fine Chemicals Generic Drug Formulations 1998 ....... q............4 g q...............................8 Liquid Formulations (Lab scale) Sulfamethoxazole + Trimethoprim Oral Suspension (400 mg + 80 mg/5 ml) 1.0.............................................1..............................0 g 3...................5....................... I. Manufacturing Sieve the components I....... Vanillin ...........................very low Sedimentation after 2 weeks: .................... 1 No........................... suspend in solution II and add the flavours III............................0 g 82....77. Properties of the suspensions No.beige Viscosity: ............ 2 Sulfamethoxazole ........10....s..0...0 g III...........6 g Kollidon CL-M [1] ..0 g Trimethoprim....not observed Redispersibility after 2 months: .........2 g Chocolate flavour ...0 g 1......... 3............. Formulations No...s............................

4..6 Ethanol .......... cool and sterilize...4 Propylene glycol Pharma [1] .10.0 Water for injectables ..................... 4................................... parabene..........0...............8 Kollidon 12 PF [1] ............ Formulation Sulfamoxole ...... 3...... Properties of the solution A clear solution was obtained...................10.......0 Parabene . heat....... Add ethanol..........0.........0.......... add the active ingredients and stir until they are dissolved...0 Trimethoprim .............0 g g g g g g g g 2........44.....5..8 Liquid Formulations (Lab scale) Sulfamoxole + Trimethoprim Veterinary Injectable Solution (400 mg + 80 mg/10 ml) 1.................30.....2 Sodium sulfite or cysteine ....... Manufacturing Dissolve Kollidon.................... BASF Fine Chemicals Generic Drug Formulations 1998 ...................................... sodium sulfite (or cysteine) in the mixture of water und propylene glycol... Remark The use of sodium sulfite in injectables is not allowed in all countries................

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

.5. BASF Fine Chemicals Generic Drug Formulations 1998 .......... Sterilisation can be done by filtration through a 0......very low 4.....clear Viscosity............8 Kollidon 12 PF or Kollidon 17 PF [1] .....2 to 0...12....... To prevent of discolouration of Kollidon in the solution during storage 0...100. Formulation Sulfathiazole ..............1 Water for injectables ....... Manufacturing Dissolve Kollidon and sulfathiazole at 70 °C in water and cool slowly to room temperature..........2 filter.........5 Sodium sulfite ....0 g g g g 2.......... Properties of the solution Appearance .......................5 % of cysteine could be added as antioxidant instead of sodium sulfite.....< 0....0...8 Liquid Formulations (Lab scale) Sulfathiazole Veterinary Injectable Solution (8 mg/ml) 1.............................................................................. Remarks A preservative can be added if needed.. 3........

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

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

........... Manufacturing (Direct compression) Pass all components through a 0.. 3.......1% Dissolution...94 N Disintegration .........5 g 94.................. 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..................9 Tablet formulations (Lab Scale) Terazosin Tablets (1 mg and 5 mg) 1........59 % 10 min ...1 mg Diameter .......1..................1% 41% 97 % 100 % 4.........1 g Ludipress [1] ..................................98................................................................1..................................0 g 5.....0.. Formulations 1 mg 5 mg Terazosin hydrochloride (Knoll) ..................... 5 min .....97 % 20 min .......................0 g 2....................................... mix intensively and press with low compression force (10 kN)...................................6 mg 6 mm 105 N 5 min < 0........0 g 1................6 mm Hardness .....98........................100 % 97...................... BASF Fine Chemicals Generic Drug Formulations 1998 .5 min Friability......8 mm sieve..........2......................... Tablet properties Weight .............0 g Magnesium stearate [2] .

....3........ 4....... Manufacturing Dissolve Lutrol F 127 and Cremophor RH 40 in water at 40 °C.... Properties of the suspension A tasteless milky suspension was obtained..q.............1........6 g Preservative ..8 Liquid Formulations (Lab scale) Terfenadine Suspension (60 mg/5 ml = 1...........92.....2 g 2...............................5..... 3................................... Water................................. Formulation Terfenadine ..................2 %) 1.0 g Cremophor RH 40 [1] .. Whilst stirring slowly add the terfenadine..... 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..................... BASF Fine Chemicals Generic Drug Formulations 1998 .............3.s..2 g Lutrol F 127 [1] ....

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

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

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

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

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

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

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

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

........... Properties of the gel A clear yellowish gel was obtained................. Cool to about 6 °C and dissolve the rest of III....18... 4.......................0 g 2....0 g Butylhydroytoluene ......6.................... BASF Fine Chemicals Generic Drug Formulations 1998 .. Formulation I...................50................... Tretinoin (BASF) ..........4 g Dexpanthenol (BASF)... Lutrol F 127 [1] .......0 mg Lutrol E 400 [1]...............0 g Cremophor RH 40 [1] .........68.................... 23 °C......... Chemical stability (12 months. Maintain cool until the air bubbles escaped.. dark) Tretinoin Dexpanthenol 96 % 100 % 5........... Water... Manufacturing Add II slowly to the clear solution I at about 40 °C.................................500 mg/100 g) 1......6.. 3....... Heat to about 50 °C and dissolve about 4 g of III in I/II..5..2.......40 mg II...7 Formulations of semi-solid drugs (Lab scale) Tretinoin + Dexpanthenol Gel (50 mg + 2.5 g III.. Remark It is important to protect the gel against light to avoid the isomerization and degradation of tretinoin......

..... Chemical stability (20–25 °C...... To the warm mixture II add solution I................. Formulation I............ dark) Months Tretinoin content Loss of tretinoin 0 3 6 9 12 0.2 Water....8..05 Luvitol EHO [1] .........0 Cremophor A 25 [1] ......2 g g g g g g g g g g g g 2....04 Propylene glycol Pharma [1] .....4........0.. Tretinoin (BASF).....0 Preservatives ....047 % 0...... 3.....046 % 0.....0....................................................7 Formulations of semi-solid drugs (Lab scale) Tretinoin Cream (50 mg/100 g) 1.............6....................................3............................ then mixture III and cool by stirring...................0........3...........1..........76........ Manufacturing Separately prepare solution I and mixture II by heating to about 75 °C. Butylhydroxytoluene .. Cremophor A 6 [1] ....0 II.........................................................3...480) BASF Fine Chemicals Generic Drug Formulations 1998 .5 III......................0 Tegiloxan ® 100 (Goldschmidt) ..................... Heat mixture III until a clear solution is formed..................0..0...........5 Perfumes ........047 % 0........0 Cetyl alcohol ......047 % 0% 0% 0% 0% Analytical method: Spectrophotometric at 358 nm in chloroform + 2-propanol 1+1 (E 1%/1 cm = 1.046 % 0........5 Glycerol monostearate .......

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

........0........................1...15........................... When a clear mixture is formed add solution I.. dark) No loss of tretinoin was measured after 1 year...................05 g Ethanol ....................0 g Cremophor RH 40 [1] ......... Chemical stability (20–25 °C.............0 g III............7 Formulations of semi-solid drugs (Lab scale) Tretinoin Gel (50 mg/100 g) 1...........6.................... 5...0..... Formulation I..0...................7 g Water... Butylhydroxytoluene ........................... 4........5 g Water.....6 g 2..........................................0..................76..q....................... Carbopol® 940 (Goodrich) ...................6............04 g II. BASF Fine Chemicals Generic Drug Formulations 1998 ..... Properties A clear yellowish gel was obtained............ Triethanolamine ..... Tretinoin (BASF)... Manufacturing Prepare suspension II and add solution III to the well stirred suspension....0 g Perfume .. 3.s..... Remark It is important to protect the gel against light to avoid the isomerization and degradation of tretinoin......

...............14...... protected from light) Months Tretinoin content 0 3 6 9 12 0..........1 g Water......................046 % = 100 % 0.05 g Cremophor RH 40 [1] ..........................5..8 Liquid Formulations (Lab scale) Tretinoin Solution (50 mg/100 g) 1.044 % = 96 % 5..... BASF Fine Chemicals Generic Drug Formulations 1998 .............................046 % 0... Introduce this warm solution slowly in solution II...s...0 g Propylene glycol Pharma [1] ..... Formulation I. (BASF).......05 g Alpha Bisabolol nat.. Chemical stability (20–25 °C..0.... Tretinoin (BASF).........044 % 0... Manufacturing Heat mixture I to 40 – 50 °C to obtain a clear solution............0 g Parabenes/sorbic acid .................. 3............0.. II... Properties of the solution Clear yellow liquid.....70... Remark It is very important to protect this formulation from light to avoid the isomerization and degradation of tretinoin..... 2..0 g Butylhydroxytoluene ...q....15. 4...0. It forms a clear yellow solution..........045 % 0.............

....191 Kollidon CL [1] .............................................................. 3.................. BASF Fine Chemicals Generic Drug Formulations 1998 ................................2..4 Ludipress [1] ..............................9 Tablet formulations (Lab Scale) Triamcinolone Tablets (4 mg) 1...................8 mm Form ..2 g g g g 2..................................................................................................... Tablet properties Weight ...............2 min Friability..0........ pass through a sieve and press with low compression force.......2 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............45 N Disintegration ................................................................... Manufacturing (Direct compression) Mix all components................................2 % 4...................biplanar Hardness......... Formulation Triamcinolone..................206 mg Diameter .....

.............2..................................204 mg Diameter ...................0..... Tablet properties Weight ...........................................................15 % 4............................ Manufacturing (Direct compression) Mix all components..................................................................65 N Disintegration .9 Tablet formulations (Lab Scale) Trifluoperazine Tablets (5 mg) 1................3 min Friability .. 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 very low compression force..... BASF Fine Chemicals Generic Drug Formulations 1998 ................. 3....... Formulation Trifluoperazine hydrochloride..................................194 g Magnesium stearate [2] .8 mm Form ..................................................1 g 2......................biplanar Hardness.......5 g Ludipress [1] ...........

.......... Carbopol® 940 (Goodrich) .g......................... 3.......0 g 2...........0 g IV.......................6 g III.............. Kollidon 30 [1] ............20.. Add the solutions III and IV...4 g II... Remark The addition of salts like sodium chloride would be possible but the consistency could be changed by such modification.....7 Formulations of semi-solid drugs (Lab scale) Ultrasonic Adhesive Gel 1.. BASF Fine Chemicals Generic Drug Formulations 1998 .... Formulation I...........5 g Water.... 4...6....1... Properties of the gel A clear colourless adhesive gel was obtained..... Preservative (e...5 g Water................... Parabenes) ....... Manufacturing Prepare solution I by heating and add II slowly to obtain a homogeneous suspension.0. Sodium hydroxide solution 10 % ....75...............2..........................0..

.........................................0 Kollidon CL [1] ...0 Aerosil 200 [4] ............. Manufacturing (Direct compression) Pass all components through a 0...........6 Magnesium stearate [2]................ Formulation Valeriana extract. mix and press with low compression force.... 3..0 Passiflora extract.........2.....231 mg Diameter ......36..........120..........9 Tablet formulations (Lab Scale) Valeriana Extract + Passiflora Extract Tablet Cores (44 mg + 30 mg) 1...........................................................44............ powder........3...... Tablet properties Weight .............................10 min Friability.........................................11.......0............................8 mm sieve.....9 mm Form ...........3 g g g g g g 2...................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...7......................biconvex Hardness..........................................................................................0 Avicel PH 101 [5] ....49 N Disintegration..................... powder...

...9 Tablet formulations (Lab Scale) Valproate Sodium Tablets (500 mg) 1................20 g Isopropanol ................................ Valproate sodium..... mix the dry granules with III and press with low compression force..............60 ml III......................... Manufacturing (Wet granulation) Granulate mixture I with solution II.................607 mg Diameter .162 N Disintegration .......0................................ Kollidon CL [1] ......5 g Magnesium stearate [2] .......................................... Tablet properties Weight .............2.7 min Friability ..................... BASF Fine Chemicals Generic Drug Formulations 1998 ..................... Remark The powder mixture was electrostatic...........................................1% 4........12 mm Form ..........................biplanar Hardness ...80 g II.. Kollidon 30 [1] ............................... Formulation I............................... pass through a sieve............................500 g Corn starch [3] ..............5 g 2.................................................................................................. 3....

................ Tablet properties Weight ..................4 % 4..............................9 Tablet formulations (Lab Scale) Verapamil Tablets (120 mg) 1........8 mm sieve and press with medium compression force.......5 – 6 min Friability.2...............3 g g g g 2.374 mg Diameter ......108 N Disintegration...................................................... Remark The tablet weight should be increased to about 400 mg...........120 Ludipress [1] ........................ Manufacturing (Direct compression) Mix all components................270 Magnesium stearate [2] ............12 mm Form ...................................................................... 3............. Formulation Verapamil hydrochloride ..........0......................................biplanar Hardness ............................3 Aerosil 200 [4] ............. BASF Fine Chemicals Generic Drug Formulations 1998 .......... pass through a 0........................................

.......................... + 40 mg + 35 mg) 1..............................................biplanar Hardness...........89 N Disintegration..13 min Friability .................................. Tablet properties Weight .... 3...................5 g 2......................583 mg Diameter ..................................................4 g Aerosil 200 [4] .75 g (BASF) Ludipress [1] ..... Formulation Vitamin A acetate dry powder ..............80 g 500... mix and press with high compression force.............................. u.............9 Tablet formulations (Lab Scale) Vitamin A + Vitamin B6 + Vitamin E Tablets (40.......2....................../g (BASF) Pyridoxine hydrochloride (BASF)............... u...................< 0......40 g Vitamin E acetate dry powder SD 50 ................12 mm Form ..............1% BASF Fine Chemicals Generic Drug Formulations 1998 ...................8 mm sieve...395 g Magnesium stearate [2] ............000 i....000 i.................................... Manufacturing (Direct compression) Pass all components through a 0.............

..........................000 i..biplanar Hardness ........................................ crystalline [10] ................0 g Sucrose...................8 mm sieve.........................0 g 2..) 1.......0...... mix and press with high compression force........290 mg Diameter ..33........300.0 g Sorbitol......0 g Stearic acid [7] ....................... + 30 mg + 200 i.......... crystalline.....................1.5........0.................................0 g Saccharin sodium ...............000 + 50...........7 min Friability..... u......4 % BASF Fine Chemicals Generic Drug Formulations 1998 .........300..30................... Tablet properties Weight ........................... u...4..........................2......300...0 g 500...............000 i....1 g Cyclamate sodium ..0 g Flavour mixture (Firmenich).....20.......................................... powder (BASF) ................. powder [6].. Formulation Vitamin A + D 3 dry powder ...........16 mm Form ..............9 Tablet formulations (Lab Scale) Vitamin A + Vitamin C + Vitamin D3 Chewable Tablets for Children (2..................0 g Mannitol .........../g (BASF) Ascorbic acid...........300......107 N Disintegration ......0 g Ludipress [1] .............0 g Polyethylene glycol 6000...... Manufacturing (Direct compression) Pass all components through a 0......................... 3.........................30. u.............

.0 g 60.......200 i........8 mm sieve.... u........ u....2. Manufacturing (Direct compression) Pass all components through a 0................................................8 mm Form . 2 Vitamin A acetate dry powder .....................................9 Tablet formulations (Lab Scale) Vitamin A + Vitamin C + Vitamin E Tablets (1.........................0 g – 20...... powder (BASF)..5...........60............4 g 500..15 min Friability ...............................1% 279 mg 8 mm biplanar 67 N 6 min < 0................. Formulations No..........0 g Kollidon VA 64 [1]....... + 60 mg + 30 mg) 1.............................0 g 2.........................0 g 5..........................0 g 100............... Tablet properties No.....................000 i.........................0 g 1....– Lactose monohydrate [8] .........60......................... 1 No....285 mg Diameter ..1% BASF Fine Chemicals Generic Drug Formulations 1998 ...........30...< 0.20................................................0 g Kollidon 25 [1] .....4 g 60..............1....................../g (BASF) Ascorbic acid...0 g – 30.........................– Talc [10] ............................ 3. 1 No.........2......................– Kollidon CL [1] ...........0 g Vitamin E acetate dry powder 50 % ...........0 g Aerosil 200 [4] .......53 N Disintegration .........................0 g 2.0 g Avicel PH 101 [5] ..................... 2 Weight .............. mix and press with medium compression force..............0 g 5..............biplanar Hardness ...............105............0 g Mannitol ...........................

....... 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.u..........u...0 g II... + 6. protected from light) No change of the clarity after some days. Physical stability (20–25 °C. Sterilization can also be performed by membrane filtration under pressure... Add the water very slowly to the well stirred mixture I...... Properties of the solutions A clear yellow solution was obtained. u. After the ampoules have been heat-sterilized.8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Calcium + Magnesium Injectable Solution (33. 3........1.../g (BASF) .....1..1 g Magnesium sulfate ........ Calcium gluconate ........5../g 15 mg Solutol HS 15 [1]..... Manufacturing Heat mixture I and the water (II) separated to about 65 °C. while they are still hot..000 i.13......) 1............ + 100 mg + 200 mg/g i. u...2.85. to eliminate any separation of the phases that may have occurred....7 Mio i....... Water for injectables ..... 5.0 g 2........000 i.... 4.. Cool to room temperature and dissolve the components III..0 g Vitamin D 3 (Cholecalciferol) 40 Mio.........0 g III. Vitamin A palmitate 1... Formulation I... BASF Fine Chemicals Generic Drug Formulations 1998 .... i........ u... they should be shaken for a short time.........

..... clear solution.0. + 20......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E + Beta Carotene Veterinary Injectable Solution (100.......... Vitamin E acetate .............4 Cremophor EL [1].4...< 9....u./g .........0 Butylhydroxytoluene .. + 10 mg + 8 mg/g) 1.. BASF Fine Chemicals Generic Drug Formulations 1998 .......u....0.5 Mio i......0 II............................0 Cremophor EL [1] .......... Properties of the solution Dark red-brown....1.... Remark In Germany Cremophor EL must be declared on the package of injectables........ while they are still hot.............. Water for injectables ..000 i.... 4....1../g (BASF) Vitamin D 3 40 Mio i.. they should be shaken for a short time. 3..5........... A clear solution is formed (= Mixture I/II)..................u.... Vitamin A propionate .. Formulation I.... to eliminate any separation of the phases that may have occurred. Heat the mixture III to 180 °C........000 i......................72...05 Benzyl alcohol .................. Heat the water II to 65 °C and add it slowly to the heated mixture I. After the ampoules have been heat-sterilized...4 2..u.0 IV... Let cool under continuous stirring of about 30 minutes......8 g g g g g g g g g 2........... Manufacturing Heat mixture I to 65 °C..... A clear solution is formed...... When the temperature is reached add the beta-carotene IV..0... hold for 3 min at this temperature and then add Mixture I/II slowly during the next 4 minutes....................9.. Sterilization can also be performed by membrane filtration under pressure.. Beta-Carotene crystalline (BASF).....3 III.........

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

16 % loss after 2 years.5.000 = 20–25 °C = 6 °C 500. protected from light) i./g Room temperature: 9 % loss after 1 year.000 600. u. 700. Chemical stability of vitamin A (2 years.000 0 3 6 9 BASF Fine Chemicals Generic Drug Formulations 1998 12 Months 15 18 21 24 .000 400.

.....................0 g Water for injectables ..10. Manufacturing The vitamins.0 g 2........ 3....000 i.................u.8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Aqueous Injectable Emulsion for Cattles (500............5 g Benzyl alcohol ..../g (BASF) Vitamin D 3 (Cholecalciferol) ........... Cremophor EL...2 g Vitamin E acetate (BASF) ... they should be briefly shaken whilst they are still hot...................000 i.........22....... to eliminate any separation of the phases.5. + 50 mg/ml with Cremophor EL) 1..........0..... u............... Chemical stability of vitamin A (Stress test at 40°C) Vitamin A content 1 Month 2 Months 3 Months 92 % 86 % 81% 5... 4........ and water at 60 °C is slowly incorporated with vigorous stirring. Remark In Germany Cremophor EL must be declared on the package of injectables....... Formulation Vitamin A propionate ...5 Mio i...u...5. butylhydroxytoluene and benzyl alcohol are mixed together at around 60 °C.........0 g Butylhydroxytoluene . + 75............... After the ampoules have been sterilized.. BASF Fine Chemicals Generic Drug Formulations 1998 ...1. stable emulsion with a viscosity of less than 30 mPa · s....0..ad 100 ml 2............. Properties of the emulsion Pale yellow milky.0 g Cremophor EL [1] ............

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 .Vitamin A found in the liver [%] 6.

..........8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Concentrates....06 g 29..... Manufacturing Heat mixture I to about 65 °C........ u.s.....0 g 6....80 g 0. miscible with water.. 2: 28 FTU 32 FTU BASF Fine Chemicals Generic Drug Formulations 1998 ......../g .../g ..7.u.....5.......06 g Cremophor EL [1] .........6.......20 g Butylhydroxytoluene .. u......7 Mio.. + 60............./g .....q.......... 1 No.....15 g Vitamin E acetate (BASF) . Properties of the solutions Yellow.......– (BASF) Vitamin D 3 40 Mio i............20 g 0.0 g Glycerol ......... + 40 mg/ml) 1.... No................10 g (BASF) Vitamin A propionate 2.u........ 2 Vitamin A palmitate 1.. 3.5 Mio i...... i.... Water-miscible (120... 1: Formulation No.....................ad 100 ml – 4....................... Clarity: Formulation No..15 g 4.......... Formulations I...................0..................50 g q.......4.......... stir well and add very slowly the warm solution II (65 °C)........ II............50 g Preservative ....u..... Water ........ clear viscous liquids.............. ad 100 ml 2..0.000 i.s.30....000 i.......

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

.....................000 i......1...... 3...0 Cremophor EL [1] ..5 Mio i....... Sterilization can also be performed by membrane filtration under pressure.....78.........4 Benzyl alcohol ... Vitamin A propionate .. After the ampoules have been heat-sterilized... 4............. Properties of the solution Clear. BASF Fine Chemicals Generic Drug Formulations 1998 ... while they are still hot..0 Butylhydroxytoluene ..u.......... Manufacturing Mix the components I and heat to 65 °C.............. + 10 mg/g) 1..05 Vitamin E acetate ...../g (BASF) Vitamin D3 40 Mio i........1 g g g g g g g 2.4 2.u....5..000 i....... they should be shaken for a short time....1...u.......0..../g......................... If the obtained yellow solution is not completely clear heat for some minutes more at 65 °C.. Formulation I II....... yellow liquid of low viscosity............ + 20..u................0....... Heat the water II to 65 °C separately and add it very slowly to the well stirred mixture I......0 Water for injectables ... Remark In Germany Cremophor EL must be declared on the package of injectables...< 15......4. to eliminate any separation of the phases that may have occurred.................8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 + Vitamin E Veterinary Injectable Solution (100..

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

..10 g 1..s.. Manufacturing Heat the mixture I to about 65 °C......... Properties of the solution Slightly opalescent.........ad 100.....7.......15 g Cremophor RH 40 [1].... BASF Fine Chemicals Generic Drug Formulations 1998 ... yellow liquid..... Formulation I....0........000 i. stir well and add very slowly the warm solution II (65 °C)..... II...................u. D/g) 1.0 g Preservative . miscible with water (Clarity: 34 FTU)....u............5..................000 i.........u.......0 g 2.. Water-miscible (120.... Water ....../g (BASF) Vitamin D 3 40 Mio i.. A + 12............. u.....q.......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Concentrate..7 Mio i.......... 3......25........... Vitamin A palmitate ..........0............/g .............03 g Butylhydroxytoluene....

..........000 i........... 3..........5 mg Cremophor RH 40 [1] .12....../g) 1.. Formulation ..................000 i.5................7......... Manufacturing Heat mixture I and solution II to about 65 °C and add II slowly to the well stirred mixture I... + 3.................7 Mio i. u............. i......../g (BASF) Vitamin D 3 40 Mio./g ......u...8 g 2..0 g Butylhydroxytoluene ......................3 g Lutrol E 400 [1] ...74....1............0 g Parabene .........0.0.8 g Sorbic acid ........... II................0....... BASF Fine Chemicals Generic Drug Formulations 1998 ........... Vitamin A palmitate.2 g Water........................... Properties of the solution Yellow clear or slightly opalescent liquid..............9 g 1...............8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Drops (30.....10....... u.u................................

/g 4.000 88% 84% 20. u.000 0 0 3 BASF Fine Chemicals Generic Drug Formulations 1998 6 Months 9 12 . Chemical stability of vitamin A (about 23 °C) 30.000 25.i.

..u...s.5... D3/ml) 1..000 i. After the ampoules have been heat-sterilized..ad 100 ml 1.u.... to eliminate any separation of the phases that may have occured. Heat the solution of the preservative in water to the same temperature and add it slowly to the well stirred vitamin mixture.q.....u... A + 5........0........ protected from light) No change was observed during 1 year... while they are still hot...... Water for injectables .... A + 10..... Physical stability (20–25 °C..8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Injectable Solutions (30..... ad 100 ml 2...........013 g Butylhydroxytoluene....000 i.0 g q.9 g 0....1..000 i.u..... Properties of the solutions Clear yellow solutions where obtained.0 –10..........000 i...0.........u... D 3 30.000 or 10.......... Manufacturing Heat the mixture of the vitamins with butylhydroxytoluene and Solutol HS 15 to about 65 °C.000 i.9 g 1.......026 g 0........ 4.u...1 g 10..1 g Solutol HS 15 [1] ..... 3..... they should be shaken for a short time.... D 3 Vitamin A palmitate ./g .......0 g Preservative .......000 i...9. BASF Fine Chemicals Generic Drug Formulations 1998 .. Formulation 30.... A + 5../g (BASF) Vitamin D 3 40 Mio i... Sterilization can also be performed by membrane filtration under pressure...u....s..7 Mio i..u....

....60...... stir well and add slowly the hot solution II (65 °C)......7 Mio i....................8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Oral Solution for Children (1.. 4.... 3.. II...s.....000 i..... Manufacturing Heat mixture I to about 65 °C................ Vitamin A palmitate ............ Properties of the solution Clear................. Physical stability (20–25 °C) No change of appearance after 2 weeks.....u..................... Water.........u......u.....u......0..ad 100 ml 2......... BASF Fine Chemicals Generic Drug Formulations 1998 ...q.... + 100 i...........0 g Preservative .......3 mg Butylhydroxytoluene ......3.....0..... Flavour ...q. yellow liquid......2 mg Cremophor EL or Cremophor RH 40 [1] .. Formulation I.......s....../g ..... /ml) 1.5......./g (BASF) Vitamin D 3 40 Mio i.....................0 mg 1.....

.... Vitamin A palmitate........25 mg Cremophor RH 40 ...... stir well and add slowly the syrup II.............1........7.............. yellow liquid....... 3.. Manufacturing Heat mixture I to about 45 °C...... Formulation I.. pH 6. Properties of the syrup Clear..........7 Mio i.u.. /ml) 1....2.000 i.8 Liquid Formulations (Lab scale) Vitamin A + Vitamin D3 Syrup (30.... 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...... 4. II..............0 g Sugar syrup 50 % ./g (BASF) Vitamin D 3 40 Mio i.....u.........000 i..ad 100 ml 2...9 g 1../g ..u..5. + 10........

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

.....0 g DL-alpha-Tocopherol (BASF) ......0 g 20.................0 g Preservative ........... Properties of the solutions Clear. Manufacturing Mix the vitamins with Cremophor RH 40 (and DL-alpha-tocopherol) at 60 °C and then add solution II (at 37 °C) slowly..q.......... u..0 g – q......1.. Water.. 3....0 g Cremophor RH 40 [1] ..............7 Mio................ BASF Fine Chemicals Generic Drug Formulations 1998 .........5 g 1. Formulations I............../g (BASF) Vitamin E acetate (BASF) .......8 Liquid Formulations (Lab scale) Vitamin A + Vitamin E Drops (25...5 g 2..... i.....000 i.5 g 1. viscous liquids..... + 50 mg/ml) 1.5.... 72........1......s............ II...5 g 5.........21..........71..........u... yellow.............. u. No.s./g ..... with stirring...5...7 Mio i... 1 No..... 2 Vitamin A palmitate 1....

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 .

................ stir well and add slowly the mixture II....6................00 g Water... The addition of butylhydroxytoluene as antioxidant would be recommendable.0...33 g 1.15.......u..... 3..7 Mio i. Vitamin A palmitate.......00 g Cremophor RH 40 [1] .............u..... BASF Fine Chemicals Generic Drug Formulations 1998 ......15. Formulation I.........ad 100 ml 2................................ Properties of the solution Colour: yellow Clarity: clear (turbity units: 25 FTU) 4..../g (BASF) Vitamin E acetate (BASF) ....... Remarks It must be tested if the ethanol concentration has a sufficient preservative efficiency..00 g Ethanol 96 % ..........8 Liquid Formulations (Lab scale) Vitamin A + Vitamin E Drops (5............000 i...... Manufacturing Heat mixture I to about 65 °C. II.......... + 50 mg/ml) 1.......5....

.....5........u.. benzyl alcohol) .0 g Preservative (e.. Sterilization can also be performed by membrane filtration under pressure.u.....000 i.... After the ampoules have been heat-sterilized............. Properties of the solution Clarity: pH: Colour: Viscosity: clear to slightly opalescent 6..0........../g (BASF) Vitamin E acetate (BASF) ...5 g Butylhydroxytoluene .... stir well and add slowly the warm solution II. Manufacturing Heat mixture I to 70 °C.........57............. 3.............10....q....s.......... + 25 mg/ml) 1.....2 g Solutol HS 15 [1] ...3 g 2. Vitamin A propionate.. while they are still hot.. Water for injectables .... to eliminate any separation of the phases that may have occured................ they should be shaken for a short time........2.. Formulation I..0 g 2..8 Liquid Formulations (Lab scale) Vitamin A + Vitamin E Injectable Solution for Sheeps (250...g.....3 yellow 45 mPa · s BASF Fine Chemicals Generic Drug Formulations 1998 ................30.... II........5 Mio i.......

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

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

. Vitamin A palmitate 1...... Physical stability (20–25 °C) No change of appearance after 3 months.....7 Mio i.......5....... miscible with water......../ml) 1.......... Manufacturing Heat the mixture I to about 65 °C........ yellow liquid. 4....0....../g (BASF) ....000 i.............6............ stir well and add very slowly the warm solution II (65 °C)...... BASF Fine Chemicals Generic Drug Formulations 1998 .....u......8 Liquid Formulations (Lab scale) Vitamin A Concentrate....... u..... II.. Water-miscible (100...ad 100 ml 2. Properties of the solution Clear...2 g Cremophor RH 40 [1]. Formulation I....5 g Butylhydroxytoluene .... 3.......... Water...s......0 g Preservative .............21..........q......

...... II..... BASF Fine Chemicals Generic Drug Formulations 1998 . u.. stir very well and add slowly the hot water (65 °C). Properties of the solutions Yellow clear or slightly opalescent solutions of low viscosity.. 1 I.....5.....0........9 g g g g g 2.............. 3. Formulations No....9 g No..............0 0...........0 10..................1 81.. Physical stability (20–25 °C......1 g Water ............. 2 3....0 5........ i....0 g Cremophor RH 40 [1]..0 g Lutrol E 400 [1] ...3....../g (BASF).7 Mio. protected from light) No change of clarity and colour after 1 year.000 i..8 Liquid Formulations (Lab scale) Vitamin A Drops (50. Vitamin A palmitate 1...............85............11.......... u.... Manufacturing Heat the mixture I to about 65 °C../ml) 1.. 4..........– Butylhydoxytoluene (BHT) ....

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

..0 g Cremophor EL (or Cremophor RH 40) [1] ..22..... while they are still hot. Formulation I.....5..917 g/ml Viscosity (25 °C): 12 mPa · s 4...... stir well and add slowly the warm solution II....... yellow Density (25 °C): 0..8 Liquid Formulations (Lab scale) Vitamin A Ethanolic Veterinary Injectable Solution (500..../ml) 1............... II. BASF Fine Chemicals Generic Drug Formulations 1998 .ad 100 ml 2....5.0 g Ethanol 96 % . Sterilization can also be performed by membrane filtration under pressure... 3......20......... Vitamin A propionate .............u........ to eliminate any separation of the phases that may have occurred......000 i.... Remark In Germany Cremophor EL must be declared on the package of injectables..... Properties of the solution Appearance: Clear............0 g Benzylalcohol ... they should be shaken for a short time..... Manufacturing Heat mixture I to about 60 °C.....0 g Water for injectables ...........5............. After the ampoules have been heat-sterilized.......

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

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

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

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

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

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

............. Add the components III to the well stirred solubilisate I/II.......3 Viscosity (25 °C): ..............................................60 mg Manganese phosphate....300 µg Thiamine hydrochloride (BASF) .....3 mg Riboflavin (BASF) ...........50 mg Kollidon CL-M [1] .........2.....0 ml Cremophor RH 40 [1]...000 mPa · s Rel......... sediment volume: ......5.....5..........................5..20........................................ Properties Appearance: ..............0 g III..... Evening primrose oil (see Remark) ....................5 g 2... Manufacturing Mix the primrose oil with Cremophor RH 40 heat to 60 °C and add slowly the warm water II....................................20 mg IV.........10 µg Nicotinamide ... crystalline ...16......0.8 Liquid Formulations (Lab scale) Vitamin B Complex + Minerals + Linoleic/Linolenic Acid Syrup 1................000 –17..................0 g II.............1..................................................... 3.......................................easy BASF Fine Chemicals Generic Drug Formulations 1998 ..........................0 g Sucrose ..............................2 g Cyclamate sodium...5 g Vanilla-flavour (Gunther) ..........................................4 mg Cyanocobalamin.....................25........0 g Citric acid ............................................... Ferric citrate ........ Finally add Kollidon 90 F to the obtained suspension portionwise with stirring........ Water..........................0......... Formulation I..........0 g Saccharin sodium ...85 % after 1 week Redispersibility:.Viscous yellow suspension (syrup) pH:............................... Kollidon 90 F [1] .3....41.......................

Remark 5 ml of Evening Primrose oil (Epopure‚.4. Prima Rosa. South Africa) contain 3.5 g linoleic acid + 0.45 g gamma linolenic acid BASF Fine Chemicals Generic Drug Formulations 1998 .

........150 N Disintegration ...2 min Friability......................q.....550 g Riboflavin (BASF)..... Tablet properties Weight .......7 g Riboflavin (BASF)..5 g (BASF)............ Polyethylene glycol 6000... Thiamine mononitrate (BASF) .................................9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C + Calcium Effervescent Tablets 1............40 g Kollidon CL [1] ..................biplanar Hardness ............................................. powder (BASF) .....................75 g Calcium glycerophosphate .............0............. III............................25 g Pyridoxine hydrochloride (BASF)...... Formulation I.............................9 % BASF Fine Chemicals Generic Drug Formulations 1998 ....................................................... crystalline .....400 g Sucrose.10 g Isopropanol .............................. powder ... Manufacturing (Wet granulation) Granulate mixture I with solution II...................... dry at 60 °C with vacuum.................................................................................................s. Ascorbic acid.....................................................20 g Calcium D-pantothenate (BASF) .........................300 g Sucrose...... powder ...............20 mm Form ........... mix with III and press with medium to high compression force............................2.........1%...........400 g Tartaric acid.................................12 g Calcium carbonate .................................2......... powder [6]...................................2 g Cyanocobalamin gelatin coated 0.............500 mg Diameter ............................ Kollidon 30 [1] ..........50 g 2...................... 3..................50 g II......................350 g Kollidon 30 [1] ...............164 g Sodium bicarbonate ............................5 g Nicotinamide ...................................

.45 g Riboflavin (BASF) ................................................ powder (BASF) ................................. Ferrous sulfate (1H20)............690 g Polyethylene glycol 6000....6 min Friability.... powder [6]......9 g 2.................6 g 2-Propanol .....................15 g II............... mix with III and press with high compression force (25 – 30 kN).............0.9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C + Ferrous Sulfate Tablets 1........... Thiamine mononitrate (BASF) ...........9 % BASF Fine Chemicals Generic Drug Formulations 1998 ............ III.......................10 g Pyridoxine hydrochloride (BASF)........ Tablet properties Weight .............................q......biplanar Hardness ........... Formulation I....................................750 mg Diameter ............................................300 g Kollidon 30 [1] .......................................... Kollidon 30 [1] .........50 g Aerosil 200 [4] ...................8 mm sieve...20 mm Form ................82 g Nicotinamide .....69 g Ascorbic acid................................................................................................................. pass through a 0....... Manufacturing (Wet granulation) Granulate the mixture I with solution II...........................1....................... 3.......s.............2..................................120 N Disintegration ....470 g Ludipress [1] ....................

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

...5 g Cyanocobalamin...241.....0 g Sucrose .0 g coated 0......17... Properties of the granules Yellow homogeneous granules dispersible in cold water........................................2 g Riboflavin phosphate sodium .0 g Pyridoxine hydrochloride (BASF)....... II...........................1..........15. 3..1% (BASF) Ascorbic acid..................................1...... powder (BASF) ............................. dry and pass through a 0. Fill 1 g of the granules in sachets.......5........4.... granulate with soluiton II......9 g Nicotinamide (Degussa) ........ Administration About 1 g of the granules (= 1 sachet) correspond to two daily vitamin B and vitamin C requirements of adults.....0 g Ethanol .4 Formulation of granules.....60 ml 2................. Formulation I.......... 4...1....8 mm sieve.....0 g Kollidon 30 [1] ..... BASF Fine Chemicals Generic Drug Formulations 1998 .... dry syrups and Iyophylisates (Lab scale) Vitamin B Complex + Vitamin C Instant Granules (2 RDA of Vitamins) 1. Manufacturing Mix the components I. gelatin .. Thiamine hydrochloride (BASF)..........50.. (or 10 g in 100 ml flaks as dry syrup)...

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. BASF Fine Chemicals Generic Drug Formulations 1998 .5. Remark Due to the high loss of riboflavin phosphate sodium it should be substituted by riboflavin.

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

Chemical stability (20–25 °C.3. 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.

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

Chemical stability (20–25 °C. dark) The following vitamin contents were determined by HPLC. 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 % .4.

...................5 g Choline bitartrate ............... ..............0 g 220........................3 – 4 min Friability.............1 g Calcium D-pantothenate (BASF) ................– Ribolfavin (BASF).... Manufacturing (Direct compression) Weigh all ingredients in.........0 g Stearic acid [7] ........ pass through a 0.......20............150................... Tablet properties No..... 1 No...0 g – 10.............................................................1% 411 mg 12 mm biplanar 69 N 5 min 0......400 mg Diameter ...............................10.0 g 5.........................................0 g – – 100.....0 g crystalline/powder (BASF) Ludipress [1] .................... Formulations No.....5...... 2 Thiamine mononitrate (BASF) ...2.........................0 g – 25..................................3 % BASF Fine Chemicals Generic Drug Formulations 1998 ............0 g Thiamine hydrochloride (BASF) .......................172............... 3..............................................................10 mm Form ............8 mm-sieve and mix....95 N Disintegration ....– – 15....................0 g 2....................0 g Nicotinamide........................0 g Pyridoxine hydrochloride (BASF) .. Press the mixture with medium/low compression force.........0 g – – 8............0 g Ascorbic acid..............0 g Folic acid .......................– Biotin (Merck) ...............2...9 Tablet formulations (Lab Scale) Vitamin B Complex + Vitamin C Tablets 1.............................................0......... 1 No..0......4 g Kollidon VA 64 [1] ....... 2 Weight ............30..0......5................................5................................................................................................– Niacin ....0 g 2...0 g Magnesium stearate [2] .....................................................biplanar Hardness .

BASF Fine Chemicals Generic Drug Formulations 1998 .4. Remark For stability reasons it would be better to substitute thiamine hydrochloride by thiamine mononitrate in formulation No. 2.

.2 µm membrane and fill the clear yellow solution in ampoules of 2 ml under nitrogen..............................400 mg Pyridoxine hydrochloride (BASF) ........50 mg Kollidon 17 PF [1] .........................160 mg Citric acid......0 ml Propylene glycol Pharma [1] ...................660 mg Nicotinamide ...4 ml Total amount .....................................10 g Parabenes ..............20......0 ml Water for injectables ....20 mg Propyl gallate .... disodium salt........4.................. dark) The following vitamin contents were determined by HPLC..about 200 ml 2..86.. II......................8 Liquid Formulations (Lab scale) Vitamin B Complex Injectable Solution 1............6 ml Hydrochloric acid 0........ keep it during 5 min under nitrogen bubbles.................270 mg Sodium hydroxide solution 1 molar ........... Thiamine hydrochloride (BASF) ....... The pH-value is about 4..........................2. Formulation I..........................................440 mg Cyanocobalamin .....1....72.....100 mg Riboflavin phosphate sodium...........880 µg EDTA.....1 molar .......... Manufacturing Dissolve the mixture I in the buffer solution II....................5......... Stability (20-25 °C....... filter through a 0... 3.... 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 ..........21...........

.... HPLC) Vitamin Content after 1 year B1 B2 B6 Nicotinamide Dexpanthenol BASF Fine Chemicals Generic Drug Formulations 1998 80 % 75 % 97 % 97 % 92 % ...........................55..........2.............................0 g Water.0 mg Vanilline.......46..............0 mg Pyridoxine hydrochloride (BASF) .......10.....55.......................5 g Glycerol .. Formulation Thiamine hydrochloride (BASF) ....5............0 mg Sorbic acid .........200..................0 mg Sucrose ....... 3.....8 Liquid Formulations (Lab scale) Vitamin B Complex Syrup 1.... propylene glycol and water.......................................120..... Stability (room temperature.....................250.....0 g Propylene glycol Pharma [1] ......... Manufacturing Dissolve the sucrose in the heat mixture of glycerol...0 g 2...................5 g Kollidon 25 [1] ..31....................................0 mg EDTA sodium ............................... cool to room temperature and dissolve the other components to obtain a clear solution.............................0 mg Nicotinamide ...5.............................................60.....0 mg Riboflavin 5-phosphate sodium ......9..........225.0 mg Dexpanthenol (BASF) ...

......................... Manufacturing (Direct compression) Pass all component through a 0................................................ mix and press with medium to high compression force.biplanar Hardness ........9 Tablet formulations (Lab Scale) Vitamin B Complex Tablets.............< 1 min Friability .........................................................25 g Thiamine hydrochloride (BASF) ........40 g Pyridoxine hydrochloride (BASF)............................................0....................................................4 % 504 mg 12 mm biplanar 68 N < 1 min 0................2... Tablet properties No........ 3........3 g — 25 g 25 g 80 g 40 g 16 g 16 g 282 g 16 g 3g 2..............513 mg Diameter ....16 g Avicel PH 101 [5] .................................282 g Kollidon 30 [1] ......................................... I 1.80 g Calcium D-pantothenate (BASF).........................................................................................16 g Aerosil 200 [4]................... 2 Weight .................... 2 Thiamine mononitrate (BASF) .73N Disintegration..............12 mm Form ........8 % BASF Fine Chemicals Generic Drug Formulations 1998 ......25 g Nicotinamide ..............................16 g Cyanocobalamin gelatin coated 0................... 1 No............ Formulations No............8 mm sieve.........................— Riboflavin (BASF)......1 % (BASF) ................ 1 No....

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

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

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

.........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...............0......22 µm membrane and fill into 2-ml ampoules under nitrogen... Formulation I.................... 3.4 g Parabene ......0 g Pyridoxine hydrochloride (BASF).. Manufacturing Prepare solution II by heating and allow to cool before dissolving the components of I in it..... 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 ..240 ml Hydrochloric acid.. Flush 5 –10 min...8 g Citric acid .. 4................2 g Sodium hydroxide solution.....4.11.960 ml 2........ 0......................6 g Nicotinamide ...............800 ml Water for injectables . II...............................0 g Riboflavin-5’-phosphate.1 molar ............ Thiamine hydrochloride (BASF) .. sodium .....1... Properties of the solution A clear yellow solution was obtained having a pH of a about 4..........5.6.................... filter through a 0... 1 molar ......... with nitrogen....25.44...................

...10 g Cyanocobalamin......... Tablet properties Weight .............................9 Tablet formulations (Lab Scale) Vitamin B1 + Vitamin B6 + Vitamin B12 Tablets (100 mg + 10 mg + 100 µg) 1.63 N Disintegration ...................biplanar Hardness ... 3...277 g Magnesium stearate [2] ............................................................................................... mix and press with low compression force.............3 % BASF Fine Chemicals Generic Drug Formulations 1998 ...................3 g 2......0...................8 mm sieve........................10 g Ludipress [1] .....................................................................................4 min Friability ...................100 g Pyridoxine hydrochloride (BASF)........................................ Formulation Thiamine hydrochloride (BASF) .12 mm Form ....... Manufacturing (Direct compression) Pass all components through a 0...................... gelatin coated 1% (BASF) ................2...................394 mg Diameter ........

................................................... pass through a 0................................. powder [6] .......5 g 2....................................... Formulation Thiamine mononitrate (BASF) .........................45 g Aerosil 200 [4]...................9 Tablet formulations (Lab Scale) Vitamin B1 + Vitamin B6 + Vitamin B12 Tablets (100 mg + 200 mg + 100 µg) 1..........0.250 g Polyethylene glycol 6000.......5 min Friability ........................................................biplanar Hardness....................... Manufacturing (Direct compression) Mix all components...102 N Disintegration .............10 g Ludipress [1] ...........2 % BASF Fine Chemicals Generic Drug Formulations 1998 ...............8 mm sieve and press with low compression force............................200 g Cyanocobalamin gelatin coated 1% (BASF) ........................2..12 mm Form .......................100 g Pyridoxine hydrochloride (BASF).......................................... 3................................ Tablet properties Weight ...............609 mg Diameter .........

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

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

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

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

.......................................10 Magnesium stearate [2] ........................... Tablet properties Weight ........... Formulation I......................................................................10 Isopropanol.......8 mm Form ....................... Kollidon CL [1] ....... Kollidon 30 [1] .....................60 III................................2 Aerosil 200 [4]........... dry and sieve through a 0. mix with III and press to tablets.. Manufacturing (Wet granulation) Granulate mixture I with solution II...............1 g g g g g g g 2...................................................9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (100 mg)..2..........100 Lactose monohydrate [8] ..200 II.....................................174 N Disintegration ................................................................330 mg Diameter ..................................9 % BASF Fine Chemicals Generic Drug Formulations 1998 .......................................................... 3.7 min Friability ...0........biplanar Hardness .........................8 mm screen.......................... WG 1........ Thiamine hydrochloride (BASF) .......................

.........................about 50 III...............4 g g g g g g 2.70 N Disintegration ........3 – 4 min Friability ...................biplanar Hardness .................................................................. 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 .........430 mg Diameter ............7 % 4.......... Kollidon 30 [1] ......10 Magnesium stearate [2] ............................................2...................................0..... Tablet properties Weight ............. Formulation I............ Thiamine mononitrate (BASF) ......... dry and sieve through a 0........... Chemical stability (30°C.. DI-TAB [9] .15 Isopropanol ..................................9 Tablet formulations (Lab Scale) Vitamin B1 (Thiamine) Tablets (300 mg) 1...................... Kollidon CL [1] ..................8 mm screen......................100 II............... mix with III and press to tablets. 3...................................... Manufacturing (Wet granulation) Granulate mixture I with solution II...................................300 Dicalcium phosphate...........12 mm Form ..............................................

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

.... Remarks These tablets could be commercialized in Europe as dietary food because all components are allowed for this application.............. Tablet properties Weight ...........8 mm sieve...................9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (3 mg) 1.......................195 Magnesium stearate [2] .......................................................................................................................... Formulation Ribolfavin C (BASF) .............. mix and press with very low compression force (4 kN).......1% Content uniformity: meets the requirements of DAB 4...................0................1 g g g g 2.......................................... 3..................................................2....................2 Aerosil 200 [4]...............................................97 N Disintegration ........................3 Ludipress [1] .............biplanar Hardness ....... 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... BASF Fine Chemicals Generic Drug Formulations 1998 ............8 mm Form ..3 – 4 min Friability......... Manufacturing (Direct compression) Pass all components through a 0............202 mg Diameter ..............

0 Avicel PH 101 [5] ..............1.........................0 Lactose monohydrate [8] ........1% BASF Fine Chemicals Generic Drug Formulations 1998 ...............8 mm Form ..........................20....................................................... dry.. pass through a 0.5 Hydrogenated castor oil (Henkel)...........10...........134 mg Diameter .....0 Corn starch [3] .... Kollidon 30 [1].....8 mm sieve...........................15............................. Aerosil 200 [4] ............0.............................< 0.............. Manufacturing (Wet granulation) Granulate mixture I with solution II...........................75....................................................2.......7 g g g g g g g g g 2..............0 II.....................biplanar Hardness ........................................................ Formulation I...82 N Disintegration.......................8 Talc [10] ...9 Tablet formulations (Lab Scale) Vitamin B2 (Riboflavin) Tablets (10 mg) 1............2................................................................... 3.............................25 III......1 – 2 min Friability ........... mix with II and press with low compression force............ Riboflavin (BASF) ....................................... Tablet properties Weight ..........................5 Water ......................

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

..................................73 N Disintegration .......................................2...9 Tablet formulations (Lab Scale) Vitamin C (Ascorbic Acid) Tablets (200 mg) 1............................................. 3..................... pass through a 0...... Manufacturing (Direct compression) Mix all components........................15.............................8 mm screen and press with medium compression force (18 kN).......................0 Kollidon VA 64 [1] .................499 mg Diameter ....................0 Ludipress [1]..............200.............4 % Dissolution.........................231................ Formulation Ascorbic acid........................ Tablet properties Weight .........0 Aerosil 200 [4] ........................... powder (BASF)......................0 Kollidon CL [1].........2 min Friability ................................5 g g g g g g 2...........> 90 % BASF Fine Chemicals Generic Drug Formulations 1998 ......2 Magnesium stearate [2] ....................biplanar Hardness ...............................25................1........2.12 mm Form ............0............ 30 min....0 – 256....................

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.

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

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

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

. Vitamin E acetate (BASF) .......6. while they are still hot......33 g Water for injectables ..... After the ampoules have been heat-sterilized... to eliminate any separation of the phases that may have occurred.......... stir well and add very slowly the hot solution II (60 °C).. Formulation I........0.. Manufacturing Heat mixture I to about 60 °C........ 4..........22..........5.... they should be shaken for a short time..s............ad 100 ml 2......0 g Preservative ......8 Liquid Formulations (Lab scale) Vitamin E + Selenium Veterinary Injectable Solution (60 mg E + 3 mg Se/ml) 1..... Sodium selenite. Remark In Germany Cremophor EL must be declared on the package of injectables.q.. II............. Properties of the solution Clear or slightly opalescent........... 3.......... colourless liquid..0 g Cremophor EL or Solutol HS 15 [1] ...... BASF Fine Chemicals Generic Drug Formulations 1998 ......... Sterilization can also be performed by membrane filtration under pressure.......

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

.......0 g g g g g 2...........2.....................biplanar Hardness..........................0 SD 50 (BASF) Sorbitol [10].............300.....620 mg Diameter .............300................................................6. 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.... BASF Fine Chemicals Generic Drug Formulations 1998 ......................................< 0........> 30 min Friability ..................................1% 4....0......... mix and press with high compression force......12 mm Form ......80 N Disintegration (water) ......8 mm sieve..0 Aerosil 200 [4] ................... Tablet properties Weight . 3.......... Formulation Vitamin E acetate dry powder ...........6................................................9 Tablet formulations (Lab Scale) Vitamin E Chewable Tablets (150 mg) 1..........0 Saccharin sodium.....2 Magnesium stearate [2]...................................................

.0 Saccharin sodium .......... Manufacturing (Direct compression) Mix all components.....................................400....................12 mm Form ........2...........0 SD 50 (BASF) Ludipress [1] ..... BASF Fine Chemicals Generic Drug Formulations 1998 ........0 Aerosil 200 [4] ........67 N Disintegration (water) .........................610 mg Diameter ..................... 3..........................0.........10..........> 30 min Friability .................. Remark These tablets could be commercialized in Europe as dietary food because all components are allowed for this application.. Tablet properties Weight .........200..........................biplanar Hardness......... pass through a 0.............1 g g g g 2...0 % 4.8 mm sieve and press with high compression force.............................................9 Tablet formulations (Lab Scale) Vitamin E Chewable Tablets (200 mg) 1.............................................. Formulation Vitamin E acetate dry powder .....................................................

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

.. II............... 3. miscible with water.........ad 100 ml 2.. 4. 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)............. Formulation I....25.............. Physical stability (20–25 °C) No change of appearance after 3 months....8 Liquid Formulations (Lab scale) Vitamin E Concentrate...q...0 g Preservative .......... Water-miscible (10 % = 100 mg/ml) 1....5 g Cremophor RH 40 [1]..... Vitamin E acetate (BASF)...... Properties of the solution Clear colourless liquid...10......................... s... Water............ BASF Fine Chemicals Generic Drug Formulations 1998 .....5......................

.... s. Water .q. 3......... Formulation I. Properties of the solution Clear or lightly opalescent....................................5........16........0 g Cremophor RH 40 [1]..8 Liquid Formulations (Lab scale) Vitamin E Drops (50 mg/ml) 1........ colourless liquid................0 ml 2.5.. Vitamin E acetate (BASF) ........79.............0 g Preservative ......................... Manufacturing Heat mixture I and solution II to about 65 °C and add solution II slowly to mixture I........ BASF Fine Chemicals Generic Drug Formulations 1998 ....... II.........

.10 Propylene glycol Pharma [1] ....... 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...... Manufacturing Mix vitamin E acetate with propylene glycol and add the water. Formulation Vitamin E acetate (BASF) .... BASF Fine Chemicals Generic Drug Formulations 1998 .....55 g g g g 2...............................7 Formulations of semi-solid drugs (Lab scale) Vitamin E Gel-Cream (10 %) 1... 4......000 mPa · s..............15 Lutrol F 127 [1] ................20 Water.. Maintain cool until the air bubbles escaped....... Viscosity at 25 °C about 120...........6... After cooling to about 6 °C dissolve slowly Lutrol F 127 in the well stirred mixture................ 3...........

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

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

............... 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....93....... The sterilisation can be done by heat at 120 °C or by filtration.. After the ampoules have been heat-sterilized. Manufacturing Dissolve phytomenadion in Solutol HS 15 heated to about 60 °C and add slowly the warm water.......... 3.... 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....... Properties of the solution A clear colourless solution of low viscosity was obtained..8 Liquid Formulations (Lab scale) Vitamin K1 (= Phytomenadion) Injectable Solution (10 mg and 20 mg/ ml) 1......... they should be shaken for a short time...... BASF Fine Chemicals Generic Drug Formulations 1998 ...0 g Solutol HS 15 or Cremophor EL [1]........s.... 87. Physical stability (Formulation No.5.....s........0g q......... 4...... Water for injectables .. while they are still hot..0 g 11.. Remark In Germany Cremophor EL must be declared on the package of injectables.....0 g 2.1...0 g 2... Formulation No........... 5...........6.q. to eliminate any separation of the phases that may have occurred. 2 Phytomenadion ..5 g Preservatives .................... 1 No.

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