PMQA LAB EXPERIMENT 1 4.

Convenience of administration
TABLETS 5. Portability of carriage and transport
▪ are solid pharmaceutical dosage forms containing drug 6. Aesthetically appealing
substances with or without suitable diluents and are prepared PROPERTIES OF COMPRESSED TABLETS
either by compression or molding. ▪ Ability to withstand the rigors of mechanical treatment
▪ Tablets without diluents are the drug products that have high (production, packaging, shipment, and dispensing)
potency, usually they are molded tablets ▪ Freedom from defects
o Molded Tablets – no diluent, purely the active ingredient ▪ Reasonable physical and chemical stability during average
- Also known as tablet triturates storage conditions.
- Usually they are moistened. ▪ Ability to release the medicament in a reproducible and
- A small amount of water (any vehicle that is suitable) will be predictable manner.
added to the active ingredient, will triturate the solvent with the PRODUCTION OF TABLETS
drug powder then it will be transferred into a mold
- Will use mold using a cylinder then it will be cut into sections
Tabletting Machines
➢ Hypodermic tablets ▪ Hopper
➢ Dispensing tablets − for storing the granulation material for compression
o Compressed Tablets − cone shaped
➢ Two methods: ▪ Feed frame/ Feed Shoe
❖ Wet granulation − for distributing the granulation material into the die cavities
❖ Dry granulation ▪ Die Cavities
➢ Tablets are formed by the process of pressing down − for controlling the size and shape of the tablets
the powder or the granular material ▪ Punches (upper and lower)
➢ They have the essential excipients (DBD) − for compacting the granulation material within the die
❖ Diluent cavities.
❖ Binder ▪ Cams
❖ Disintegrant − for guiding the punches
➢ Often times it also has compression aids (LAG) TYPES OF TABLETTING MACHINES
❖ Lubricant 1. Single Punch Press
❖ Anti-adherent This is consist of a
❖ Glidants o Hopper
➢ Enteric coated, Chewable, Multiple-compressed o Feed shoe
o Weight adjustment collar
MOLDED TABLETS OR TABLET TRITURATES ✓ Clockwise – reduces the fill weight
▪ These are usually made from moist material using triturate mold ✓ Counter-clockwise – increase the fill weight
that gives them the shape of cut sections of a cylinder. o One set of the cavity and punches (upper and lower)
▪ Mixtures of medicinal substances and a diluent usually o Discharge chute
consisting of lactose (and powdered sucrose in varying o Cam
proportions). o Upper adjustment collar
▪ The powders are dampened with solutions; pressed into molds, - Responsible for the position of the lower punches
removed, and allowed to dry. - The ejection of finished tablet depends on this part
▪ Dispensing Tablets
− These tablets provide a convenient quantity of potent drug
that can be incorporated readily into powders and liquids
− These tablets are supplied primarily as a convenience for
extemporaneous compounding and should never be
dispensed as a dosage form.
− Used by pharmacist 2. Multi-station Rotary Tablet Machines
− Contain very potent formulation − For increase production output, these machines offer great
▪ Hypodermic Tablets advantages. A head carrying a number of sets of dies and
− These are soft, readily soluble tablets and were originally punches revolves continuously
used for the preparation of solutions to be injected.
− Used by physicians
− Contain very potent formulation
COMPRESSED TABLETS
▪ These tablets are formed by the process of pressing powdered,
crystalline or granular materials, alone or in combination with
excipients to form a compact adherent mass of predetermined
shape 3. High Speed Rotary Tablet Machines
ADVANTAGES OF COMPRESSED TABLETS − increasing the number of stations (i.e. sets of punches and
1. Precision of dosage dies, in each revolution of the machine head)
2. Durability of the physical characteristics for extended periods of − improvement in “feeding” devices
storage − installation of dual compression points
3. Stability of chemical and physiological activities of the drug
 − Have 3 or more sets of dies and punches ❖ Fructose (levulose)– gives dark brown color and
bitter taste
1.4. Mannitol
 This another sugar is used for special situations, due
to its high cost. It as sweet and obtained as powder or
4. Multi-layer Rotary Tablet Machines granules.
− The rotary tablet machines have been developed into  It is extensively used for chewable tablets.
models capable of producing multiple-layered tablets.  Example of a sugar alcohol
These machines are able to make one, two or three  Not commonly used because it is costly/expensive
layered tablets. 1.5. Microcrystalline Cellulose (MCC) (Avicel)
 a very expensive tablet diluent
1.6. Hydrolyzed starch with dextrose (Celutab)
 Its concentration is 95 to 96%; it contains 4 to 5%
polysaccharides. It is also used as a base for
chewable tablets due to sweet taste and pleasant
“mouth feel”
TABLET ADDITIVES AND COMPONENTS  Starch is an example of a polysaccharide specifically a
Additives or Excipients (inactive ingredients/inert ingredients) homoglycan, upon hydrolysis may yield to several units of
furnish bulk or volume to the tablets and are classified according to glucose
their functions as follows: 2. Binders or Adhesives or Granulating Agents
Essentials: D,B,D These substances “glue” powders together and cause them to
Compression: LAG form granules.
Miscellaneous: C,F - Added in the dry form and is activated by addition of water or
1. Diluents or Bulking Substances (Fillers) other solvents (glycerin, alcohol)
- Designed to make up the required bulk of a tablet - Promote cohesive compacts during direct compression
- Example: The needed active ingredient is so small in terms of - Overwet → the granules will be too hard, will not allow proper
amount, it cannot be compressed alone, this is the time that we compression
would need to add the fillers - Underwet → the granules will be too soft, easy to crumble
- Sometimes, it improves the cohesion of the formulations or the Examples of raw materials employed as binders are:
drug powders o Natural gums (acacia, tragacanth)
These are substances that make up the major portion of the o sugars (sucrose)
tablet, usually: o starch gelatin
1.1. Lactose USP – most often used because of the following o polyvinyl pyrolidone (PVP) in alcohol
advantages: o cellulose derivatives (ethylcellulose, methylcellulose in
 Best and most widely used diluent or filler, it possess
chloroform)
characteristics of an ideal diluent
 it is stable and does not react with most medicinal o Gelatin - 10-20% solution
substances o Glucose - 50% solution
o Polyvinylpyrrolidone (PVP) - 2% conc.
 its rapid solubility in water means quick release of the
o Starch paste - 10-20% solution
drug substance
o Sodium alginate
 non-hygroscopic and possess a high melting point, so
o Sorbitol
it is not softened by frictional forces of machine
compression 3. Disintegrants
 Hygroscopic – it absorbs moisture and does not turn into solution These are substances or agents added to compressed tablets to
 Deliquescent – they would take up the moisture and turn into cause them to “break apart” or disintegrate, when placed in an
solution aqueous medium.
1.2. Starches (wheat, corn, rice and potato) - Oppose efficiency of the binder
 Wheat: Triticum aestivum
 Corn: Zea mays
Examples of raw materials employed as disintegrants are:
 Rice: Oryza sativa o Starch – the best choice of formulators
 Potato: Solanum tuberosum o natural gums –due to its property to swell in water e.g.
 they are employed as binders and disintegrants bentonite
 it contains 12 to 14% water o cellulose derivatives (methocel, Avicel, alginates SCMC)
 stored energy in plant materials o Starch - 5-20% of tablet weight.
 used to stabilize hygroscopic drugs as well as to protect the
o Starch derivative – Primogel and Explotab (1-8%)
tablets from deterioration
 never used as a glidant o Clays- Veegum HV, bentonite 10% level in colored tablet
1.3. Sucrose only
 Sweet sugar o Cellulose
 Advantage: It is sometimes added to provide o Cellulose derivatives- Ac- Di-Sol (Na CMC)
additional sweetness, but its’ main use is as a binder o Alginate
because of its cohesive property. o PVP (Polyvinylpyrrolidone), cross-linked
 Disadvantage: Oxidizes (turns dark brown), when it Superdisintegrants:
comes in contact with acidic and basic substances. o Swells up to ten fold within 30 seconds when contact
 May lead to invert sugar once hydrolyzed: water.
❖ Glucose o Example:
 ❖ Crosscarmellose- cross-linked cellulose,
❖ Crosspovidone- cross-linked povidone (polymer),
❖ Sodium starch glycolate- cross-linked starch.
o A portion of disintegrant is added before granulation and a
portion before compression, which serve as glidants or
lubricant. Evaluation of carbon dioxide in effervescent
tablets is also one way of disintegration
4. Lubricants or Glidants or Anti-adherents
These are substances which:
o Promote easy ejection of tablets out of the tableting machine
o improve the rate flow of tablet granulation
o prevent adhesion of the tablet, material to the surface of
the dies and punches
o reduce particulate friction
o facilitate the ejection of the tablets from the die cavities
o Poor lubrication can be detected by the “scratch” marks on
the edges of the tablets; another is the “screeching” sound
of the machine.
o Lubricants reducing friction on walls of tablets and walls of die
cavity
o Glidants promote the flow rate and reducing the friction among
the particles of tablets
o Anti-adherents reduce the sticking or adhesion of the tablet
formulation to the faces of the punches
Examples of raw materials employed as LUBRICANTS are:
o stearates of magnesium (and calcium) and zinc
o talcum powder (asbestos free)
o sodium benzoate
o mixture of sodium benzoate and sodium acetate • colloidal
silicone dioxide
o Leucine
o carbowax 400
Examples of raw materials employed as GLIDANTS are:
o Corn Starch – 5-10% conc.
o Talc - 5% conc.
o Silica derivative – Colloidal silicas such as Cab-O-Sil,
Syloid, Aerosil in 0.25-3% conc.
5. Coloring Agents
Coloring agents are added to tablet granulations for the
following purposes:
o for improvement of aesthetic appearance
o to provide control of the product during its manufacturing
o as a means of identification
o The most common method of adding colorant to a tablet
formulation is to dissolve the dye in the binding solution,
prior to the granulation process.
o Another approach is to adsorb the dye on starch or
calcium sulfate, from its aqueous solution. The resultant
powder is dried and appears uniformly blended with other
ingredients.
COLORANTS
o FD&C Red No. 2 (amaranth)
- causes cancer in rats, unproven safety
o FD&C Red No. 4 (Ponceau Sx)
- found in maraschino cherries and ingested drugs; only
used in external drugs and cosmetics (can be used in
food)
o FD&C Yellow No. 5 (tartrazine)
- causes allergic type reaction in many people
 ● Examples are dried lactose, anhydrous lactose, calcium phosphate,
mannitol, sorbitol and Avicel.
6. Flavoring Agents
These are substances added to tablet formulations mainly to “mask” the
undesirable flavor of certain medicaments
● Examples of raw materials employed as flavoring agents:
○ sugars (natural or artificial)
○ essential oils ( peppermint, lemon, orange, vanilla, strawberry,
banana, and the likes) –
○ fruit acids (citric acid, tartaric acid, malic acid)
FLAVORANTS
● Taste of drug substance itself
○ Salt – cinnamon, orange, raspberry, butterscotch, maple
○ Bitter - wild cherry, chocolate mint, licorice ● Raw material → Weighing → Screening → Mixing →
○ Sweet - fruit, berry, vanilla Compression
○ Sour or acid – citrus/ Cherry juice
B. Granulation by Compression
FLAVORING METHODOLOGY
● This method is adopted for tablets components that are sensitive to heat
1. Blending – fruit flavors blend with sour taste, bitter with salty, sweet and sour
moisture or both. It is further divided into two methods namely
2.Overshadow – flavor with longer and stronger taste is added to the obvious
1) Slugging by a Tablet Press
taste. For after taste
● Also similar to dry granulation method
3. Physical – formation of insoluble compounds of the offending drug
● Granulation by slugging is the process of compressing dry powder of
4. Chemical – use of the processes of adsorption or complexation
tablet formulation with tablet press having a die cavity large enough
5. Physiological - anesthetizing the taste buds
in diameter to fill quickly.
Sweetening agents ● With 1 inch of diameter
2) Use of Chilsonator
● For chewable tablets: Sugar, mannitol.
● It consists of 2 rollers controlled by hydraulic drums. The tablet
● Saccharin (artificial): 500 time’s sweeter than sucrose Disadvantage:
materials are fed the hopper to the rollers which contain a spiral
Bitter aftertaste and carcinogenic
impeller to de-aerate the powder.
● Aspartame (artificial) – Disadvantage: Lack of stability in presence of
● After passing the roller, the compacted mass resembles a thin cake.
moisture
The aggregates are formed from the “cake” are screened to produce
● Steria is more safer
the tablet granulation.
7. Adsorbents ● There is no need for screening in this machine
● It was like has been in slugging
● These are substances capable of holding quantities of fluids or moisture
in an apparently dry state.
● Examples of raw materials employed as adsorbents –carbonates of
magnesium and calcium
○ oxides of magnesium and aluminum
○ kaolin, bentonite
○ Veegum
Preparation of Tablet Components for Compression II. Wet Granulation Method
● I. Dry Granulation Method ● The most widely used method of tablet preparation. Its popularity is due
○ Under it we have Direct Compression And granulation by to greater probability that the granulation will meet all the physical
compression requirements for the compression of good tablets.
● Also called “Pre-compression” or “Double Compression Method” Disadvantages:
● This method is applicable to tablet ingredients that are or have sensitive ● the number of several steps involved
to moisture ● it requires longer processing time a
● unable to withstand elevated temperature during drying ● labor cost is high.
● sufficient inherent binding or cohesive properties
Steps in the wet method are:
Preparation of Tablet Components for Compression 1. Weighing of the ingredients.
2. Mixing them in a suitable mixer or blender.
1. Weighing of ingredients 3. Granulation into a damp mass by the addition of a binding solution.
2. Mixing of ingredients in a suitable mixer or blender 4. Screening the mass by forcing through a 6- or 8- mesh screen.
3. Slugging by using flat face punches 7/8 to 1 inch diameter 5. Drying in suitable ovens or fluid bed dryers.
4. Dry screening of slugs through a mesh screen (by hand) or through a
6. Dry screening through smaller mesh screen.
fitzpatrick comminuting mill
7. Lubrication in a suitable blender.
5. Lubrication through a suitable blender 8. Compression into final tablets
6. Compression into final tablets
Raw materials → Weighing → Screening → Wet massing →
The steps included in the dry method are as follows:
Sieving/Milling → Drying → Screening → Mixing → Compression
Raw material → weighing → Screen → Mixing → Slugging → Milling ● In drying you can use oven or fluid bed dryers
→ Screening → Mixing → Compression C. Special Procedure
Slugging use in the tabletting machine by using flat face punches about 1 inch. 1. Spray-drying
diameter ● This method consists of bringing together a highly dispersed liquid
A. Direct Compression and a sufficient volume of hot air to produce evaporation and drying
of the liquid droplets. Thus forming granules, ready for compression,
● A few crystalline substance like inorganic salts (NaCl, NaBr and KCl) may after the active ingredients are mixed in.
be compressed directly (without any excipients), but majority are not easy ● It was preferred method for thermally or heat sensitive materials
to tablet. ● The feed liquid may be a solution, slurry, emulsion, gel or paste,
● Can only use without slugging provided it is “pumpable” and capable of being atomized
● To remedy this problem, the uses of directly compressible vehicles are 2. Spheronization
advised. These are inert substances, which may be compacted with no ● It is a form of pelletization which refers to the formation of spherical
difficulty, and may do so even when mixed with drugs particles from wet granulations. Since the particles are round, they
have good flow properties, when dried

MO #1 ACETAMINOPHEN TABLET
Uses of Raw materials
1) Acetaminophen: Antipyretic, analgesic (API)
● It has weak antiinflammatory properties
2) Lactose: Diluent/ FIller
3) Cornstarch: Binder, disintegrant
4) Starch paste (10%): Binder
5) Talc: Lubricant /Glidant
6) Magnesium stearate: Lubricant
Method employed: Compression method: Wet granulation
N-APAP - N-acetyl-p-aminophen
S/E= hepatic necrosis >4g within a day you have taken
● hepatic necrosis it depletes the glutathione in the body which
bind the toxic metabolites of paracetamol which is NAPQI - N-
Acetyl-p-benzoquinone bind in the glutathione in the liver
which lead to hepatic necrosis
● Antidote N-Acetylcysteine or N-AC Fluimucil
● INN or International Nonproprietary Names - Acetaminophen
while in the Philippines it was Paracetamol
PMQA LAB : EXPERIMENT 2
Capsules
● are solid dosage form in which the drug is enclosed within either a
hard or soft soluble container or “shell”
● They are usually formed from gelatin; however, they also may be
made from starch or other suitable substances.
○ Gelatine is a protein found in animal collagen. It goes
partial hydrolysis
○ It has two types:Type A from pork skin undergoes acid
hydrolysis. Pork skin gelatine contributes to plasticity and
clarity. It reduces haziness/cloudiness. It was normally use
in SGC/Soft gelatine capsule
○ Type B from Cow bone undergoes Alkaline hydrolysis.
While cow bone is hazy and brittle. It was normally use in
HGC/Hard gelatin capsule
Hard Shell Capsules
● Available from 000 (largest) to 5 (smallest)
○ Size 5 can contain 100mg while 000 is 950mg
○ Size 000 is use for veterinary and for suppository
● Larger bolus capsule: Veterinary use in large animals
● Size 00 is usually the largest capsule size used orally for
humans. And size 00 can contain 650mg
● Size 000 are sometimes used to encapsulate the medication for
rectal or vaginal use.
● The capsule should be moistened with lubricating jelly or water
before insertion
● The weight capacity for a given capsule size is highly dependent on
the density of the powder
● Opaquant of capsule shells- Titanium dioxide
○ It normally can buy already made capsules for the blind
studies. They normally use in studies for there appearance
especially for if the drug product is vegetable plant material
and they close it capsule shells. And for them to be easy to
take and conceal the powder contents.
● In addition to gelatin, capsule shells may also contain dispersing
agents, hardening agents e.g., sucrose or preservatives.
● Usually 12-16% or 10-15% water must be present
○ The temperature is maintained at 100 F
○ Note for moisture content. At high moisture content the
capsule can become soft and tacky. When it is low in
moisture the capsule becomes brittle.
● These are especially useful when it is necessary or desirable to
conceal the powder contents, eg, when dispensing powders with an
unappealing appearance or making for blind studies
● In addition to gelatin, capsule shells may also contain dispersing
agents, hardening agents e.g., sucrose or preservatives.
● Usually 12-15% or 10-15% water must be present
Effect of lack of moisture in capsules shells
● Causes the shell to become hard and brittle, affecting dissolution and
bioavailability.
● Proper container: Tight containers that maintain a constant,
adequate relative humidity
● Capsules supplied by the manufacturer in paper boxes should be
transferred to amber glass powder squares or other containers.
Effect of lack of moisture in capsules shells
1) Calculate the weight of the powder to be filled into each capsule
= wt of all active ingredients per capsule + wt of any needed diluent
Size 5 capsules has capacity of 100mg
25mg active capsules + diluent
25 x 30 for number of capsules needed = 750mg
100mg x 30 = 3000
3000-750 = 2250mg and that will be needed diluent
2) A diluent may be needed in the following situations:
● If the amount of powder per each capsule is less than the minimum
weighable quantity (MWQ) for the balance being used, an inert solid
diluent must be added to the active powder ingredients to give
desirable weight.
● Because the smallest capsule sizes numbers 4 and 5, are difficult for
some compounders to handle, if the quantity of powder is more than
the MWQ, but is so small that a size 4 or 5 capsule shell is needed,
diluent may be added so that a larger capsule size can be used.
● Size of capsules
000-950mg 00 - 650mg 0 - 450 mg
1 - 300mg 2 - 250mg 3 - 200mg 4 - 150mg 5 - 100mg
● Occasionally, the amount of powder per dose does not fit properly in
any given capsule size; it is too much powder to fit one size but gives
void space to in the next larger size. If this occur, an inert solid diluent
may be added to adjust the powder volume to the larger size capsule
● When hand filling capsules, a wellpacking diluent may be added to a
crystalline or granular powder to improve its ease of packing.
● Lactose monohydrate (non-spray-dried variety) and cornstarch
are two diluents that work well for this purpose
● When using a capsule-filling machine, an inert diluent may be needed
to improve the flow of the powder so that the capsules of uniform
weight are obtained. Also, the capsule-filling machine may not have
plates for all capsule sizes, therefore it is required to add diluent to
accommodate capsule sizes available to you.
Procedure for hand filling capsules with dry ingredients
1. Prepare the powder using the techniques and procedures for particle size
reduction and blending.
● With use of trituration
2. Place the powder mixture for all capsules on an ointment slab or pad. Using
a spatula, arrange the powder into a compact, flat powder bed of uniform
thickness. This is referred as “blocking the powder bed”
3. It is now a standard procedure to use disposable gloves.
4. Separate the capsule from the body of the capsule shell and repeatedly
press the open end of the body of the shell downward into the powder bed.
● This is called punching capsules
MO#2 Ferrous sulfate capsule
Raw Materials:
• Ferrous sulfate (20% elemental iron): active ingredient/prevention of IDA
• Talc: Diluent
Dosage Administration:
● Iron is best absorbed when taken on an empty stomach, with water or fruit
juice (adults: full glass or 8 ounces; children: half glass or 4 ounces), about
one hour before or two hours after meals.
● However, if stomach upset occurs, lower doses may be given to start with,
and the iron can be taken after food
● Usually available as extended-release capsules: Swallow whole with full
glass of liquid. Don't chew or crush. Take with or immediately after food to
decrease stomach irritation.
● According to USP: Ferrous sulfate per 100 mL should contain NLT 3.75
g and NMT 4.25 g
● As elemental Iron: should contain NLT 0.75 g and NMT 0.85 g
● It was normal have black stool when taking any iron medication
Amounts of ELEMENTAL (PURE) IRON
300 mg of Ferrous gluconate contains 35 mg of elemental iron (11.6%),
300 mg of ferrous sulfate contains 60 mg of elemental iron (20%).
300 mg of ferrous fumarate contains 100 mg of elemental iron (33%),
● sangobion 250mg has 70 mg elemental iron and commonly see in our
market.Ferrous fumarate is Sangobion prenatal FA it contains of 600
Ferrous fumarate and 118.8 elemental iron
Storage:
● Store in a cool, dry place away from direct light, but do not freeze.
● Not to be exposed to avoid oxidation to ferric state. For powder form
Packaging and Labeling
CONTAINER:
● Well-dried bottles preferably sterilized
LABELING REQUIREMENT:
● Content of elemental Fe and Ferrous sulfate
Brand names
• Feosol® • Feosol® Caplets • Fergon® • Slow FE®
Sorbifer Durules And Sangobion for philippines brand