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INDUSTRIAL PHARMACY

Tablet
Tablets are solid dosage form containing unit dose of one or more active ingredients
along with the necessary excipients and prepared by compression of the powder
particles.
Characteristics:
1. It is solid dosage form.
2. It is usually orally taken.
3. It is a unit dosage form.
4. It is prepared by compression.
Potential advantages:
1. Better chemically, physically and biologically stable.
2. Accurate dose of the drug.
3. It can be mass produced under strictly quality control.
4. It contains low price.
5. It is safe to administrate.
Disadvantages:
1. Initial investment is expensive for buying machineries.
2. It is responsible for local irritation and damage stomach.
3. Improper formulation may cause bioavailability problem.
4. It is tough for children/older to take.
5. It is not suitable for immediate administration.
Ideal Characteristics:
1. The dose should be accurate.
2. Appearance should be good.
3. Drug should be released from the tablet.
4. Should be biocompatible.
5. Packaging should be effective and safe.
6. Should be physically, chemically, microbiologically stable. | 1
7. Color and Size should be attractive.

Md. Asif Hasan Niloy


5th Semester 24 BATCH
Tablet
Course Instructor: MD.SELIM HOSSAIN
Classification:
A. On the basis of drugs release profile:
1) Immediate release Tablet (IR): Drug should be released immediately after
injection of the tablet. e.g., Paracetamol.
2) Modified release Tablet (MR): These are sub-divided into two types
3) Extended release tablet(ER): Drug is released slowly for a long time after injection
of the tablet. e.g., Metformin
4) Delayed release Tablet: The release of the drug is delayed for some time after oral
administration of the tablet. e.g., Aspirin 75mg, Omeprazole.
B. On the basis of coating:
1) Uncoated Tablet: No coating applied over the tablet. e.g., Paracetamol
2) Coated Tablet:
a) Sugar coating Tablet. e.g., Vitamin tablets
b) Film coating Tablet. e.g., Metronidazole
c) Enteric coating Tablet. E.g., Aspirin
C. Some common types of tablet found in market:
1) Conventional Tablet. Example: Paracetamol
Objective:
o To achieve rapid, complete drug release in vivo.
o To facilitate for children and older.
Characteristics:
a. It is taken with small amount of water. d. Usually taken for systemic action.
b. Rapid disintegrate in GIT. e. Single or multi-layer tablet.
c. Rapid dissolution. f. May be coated or uncoated.
Formulation Aspect:
1. Diluents are used when the weight of the tablet is small.
2. Binder.
3. Disintegrating Agent. 22
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4. Fraction reducing agent to prevent fraction between particles.

Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

2) Chewable tablet. Example: Antacid, Vitamin tablets.


Objective:
To achieve quick, complete disintegration of the tablet in vivo and thus achieve
rapid & quick effect.
To facilitate for children and Elder person.
Characteristics:
a. Disintegrate in the mouth.
b. Drug dissolute occurs in GI fluid.
c. Use for both the systemic and local action.
d. Usually uncoated tablet.
Formulation aspect:
1. Diluents: Sorbitol & Mannitol.
2. Binder.
3. No disintegrating agents are used.
4. Friction reducing agent are used.
5. Coloring and flavoring agent.

3) Effervescent tablet. Example: Aspirin tablet.


Characteristics:
Tablet should be drop in a glass of water and resulting solution should be taken
orally.
CO2 is evolved which causes the tablet disintegrate rapidly in vitro.
Uncoated
Taken for quick systemic action.
Objective:
To achieve quick and complete disintegration of the tablet in vitro in order to

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achieve rapid effect. |
To reduce gastric irritation.

Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Formulation aspect:
a) Gaseous disintegrated CO2 is generated by reaction of an acid (tartaric acid/citric
acid) and a Na carbonate/bicarbonate.
b) Water soluble friction reducing agents are used. (HPMC) Hydroxyl Propyl Methyl
Cellulose Polymer.
c) Binder may not be used.
d) Flavoring and coloring agent is used.
e) CO2 covers the taste bards of the term and helps in taste masking.
f) Packages must be completely water proof.
4) Compressed Lozenges: Example benzocaine, analgesics.
Objective:
To dissolve slowly in the mouth.
Used for localized effect in the mouth.
Characteristics:
Slowly disintegrate in the mouth.
Slow release tablets for local drug treatment.
Use for both the systemic and local effects.
Harder than ordinary tablets.
Formulation aspect:
1) No disintegrating agents are used.
2) Coloring and flavoring agent.
3) Particular filler and binders are used. Gelatin is commonly usable binder.
4) Have high mechanical strength and low porosity. Which is responsible for slow
release.
5) Sublingual tablets and buccal tablets: Example - prochlorperazine maleate for nausea
Objective:

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To release drug in the mouth followed by systemic uptake of the drug. |
Used for localized effect in the mouth.

Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Characteristics:
1) Drug effect can obtained without first-pass liver metabolism.
2) Sublingual tablets are placed under the tongue and
3) Buccal tablets are placed in the side of the cheek.
4) Tablets are often small and porous.
5) The latter facilitating fast disintegration and drug release.
6) They remain in position, releasing drug, for 12 hours.
Formulation aspect:

Tablet Formulation: API + Excipients


Excipients: They are inert which added to the tablet in order to solve manufacturing or
formulation problems.
Types of Excipients:
A. Diluents/Fillers: Diluents provide the necessary volume and weight in case of tablet
containing low dose of drug. The minimum weight of a tablet should be at least 50mg.
Example: Lactose, microcrystalline cellulose, calcium carbonate, sucrose, dextrose.
Characteristics: (1) Chemically inert.
(2) Non hydroscopic.
(3) Biocompatible.
(4) Cheap.
(5) Good compatibility.
(6) Acceptable taste
B. Binder: They are incorporated to the tablet formulation in order to form stable
granules as well as tablets. Binders bind together the tableting materials and increase
sufficient mechanical strength to the granules and tablets.
Types: Binders are two types

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Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Example: starch, paste (5-25%), polyethylene glycol, sucrose, gelatin,


b) Dry binder: Drug + Diluent + Disintegrant + binder
High pressure
Slugs tablet
Reduction/communication
Compression

Tablet
Example: Cellulose, methyl cellulose (1-5%), PVP (2-10%), Starch.
STARCH PASTE BINDER
Concentration: 5 to 25%
Characteristics: 1) Commonly used binder.
2) Time consuming process.
3) Insoluble in cold water.

POLYVENYLPYRROLIDONE
Concentration: 2 to 8%
Characteristics: 1) Soluble in water and ethanol.
2) Has different viscosity grade.

HYDROXY PROPYL METHYL CELLULOSE (HPMC)


Concentration: 2 to 8%
Characteristics: 1) Soluble in water and ethanol.
2) It is dry

C. Disintegrant/Disintegrating agent: The agent which helps to break down the tablet is
called disintegrating agent.
Types: On the basis of adding position it can be divided into two types:
1) Intra granular: Required to convert primary particles from granules. 66
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2) Extra granular: Required to covert granules from tablet e.g. Starch (conc. is 5-10%)
Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

SUPER DISINTEGRANT: The disintegrant which is swelled rapidly, instantly


disintegrated and can act at low concentration. e.g., Na-starch glycolate (2-8%),
Cross povidone (1-5%), Cross carmellose (1-5%). ##Carmellose = Carboxy methyl
cellulose.
Mechanism of action:
o Facilitate water uptake within tablet.
o Swell and exert pressure to cause rapture of the tablet.
o Form CO2 by reaction which cause rapid breakdown of the tablet.

D. Lubricating agent: The agents which reduces friction is called lubricating agents. On
the basis of friction these agents are classified into
1) Glidant: Remove particle-particle friction in the hopper and improve flow
property of tableting materials. e.g., Silicon dioxide/Colloidal silica (1-5% mostly
used in pharmaceuticals), Talc (1-5%), calcium scilicet (0.5 to 2%)

2) Lubricant: They reduce friction between the side surface of the tablet and the die
wall. On the basis of mechanism these are subdivided into
i. Boundary Lubricants: These produce a solid particular film between the surface
and the wall. e.g., Mg-stearate (o.2-2% mostly used in pharmaceuticals.
hydrophobic in nature), Ca-stearate (o.5-4%; hydrophobic in nature),
Polyethylene glycol (2-10%, hydrophilic in nature).

ii. Fluid Lubricants: These produce a liquid particular film between the surface and
the wall. e.g., Live mineral oil (1-3% mostly used in pharmaceuticals.
hydrophobic in nature).

3) Anti-adherent: It reduces the friction between the punch phases and surface of the
tablet. e.g., Mg-stearate (0.5-2%), Talc (1-5%)
77
|

Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Problems arise when large amount of lubricants are used.


a) If the agent is hydrophobic it should not go to dissolution.
b) Increases friction and it decreases flow property.

Steps involving tablet production:


Direct compression: Drug + Filter + Disintegrant + Glidant

Blending

Compression.
The materials which are available in crystalline form can be used in direct compression to
prepare tablet.
Tablet prepared by direct compression: Ranitidine, Misoprostol.
Problems:
Poor compaction property.
Excipients are too much expensive.
Excipients used in direct compression: Sorbitol, mannitol, anhydrous lactose, directly
compressible starch, micro crystalline cellulose.
Dry granulation: Drug + Filler + Lubricant + Binder

Blending

Pre-compression/slugging

Reduction

Sizing

Blending (Glidant, lubricant, disintegrant)

Blending

Compression.
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Tablet prepared by dry compression: Aspirin, ca-lactate


Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Wet granulation: Drug + Filler + Binder/Adhesive



Blending

Wetting (Binder, Adhesive, water)

Granulating

Drying

Sizing

Blending (Glidant, disintegrant)

Compression.
Tablet prepared by wet compression: Paracetamol, ciprofloxacin.
Compression: Reduction of the bulk volume by removing gaseous substance with the
apply of pressure.
Consolidation: Increase mechanical force due to particle-particle interaction.
Compaction: Combination of two phases (compression + consolidation) to produce
compact material or tablet.

Events during compression:


1) Particle rearrangement: Due to applying pressure volume of powder bed is reduced
by placing small particles into voids between larger particles.
2) Fragmentation of particles: Particles fragmentation occurs for applying pressure.
(i) Elastic Deformation: Particles return to the original shape upon release of stress.
(ii) Plastic Deformation: Deformation does not completely recovered after release
of the pressure.

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Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

3) Cold welding or Fusion welding: Bonding between particles due to mechanical


interlocking of irregular shaped particles.

4) Deformation of the solid body: Development of the Vander walls force and
hydrogen bonds between particles which is smaller than 50nm.
5) Elastic recovery or Decompression & Recovery: With increasing pressure the
density of the particles increases. At a moment when excess amount of pressure
applied forms deformation.

Tablet Press/Machine:
Basic Parts: 1. Die: It requires to filling tablet materials.
2. Punches: It helps in compression.
These are two types:
a. Upper punch.
b. Lower punch.
Tablet Press/Machine: Tablet machines are basically two types
a. Single punch machine
b. Multi punch machine.

Single punch machine Multi punch machine.


1. In case of filling we get exact 1. Excess dyes are rejected.
weight.
2. Upper punch move and lower 2. Upper and lower both punches
punch is fixed. move.
3. 200 tablets per minute. 3. 10,000 to 70,000 tablets per
minute.

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Tablet Machine Brand Name 1. Cudmach 2. Kikusui 3. Sviac
4. Killian 5. Hatta 6. Fette 10
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7. Monusty 8. Courtoy 9. Stokes.
Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Tablet press tolling: 1. Upper Punch


2. Lower Punch
3. Die
According to size tablet tooling sets are three types
1) BB: For small size tablets.
2) B: Identical to BB, but lower punch is small in length.
3) D: Large tablets.

Steps for formatting tablet: 1. Die filling


2. Compression
3. Tablet ejection.

Defects of tablet: 1. visual defect


2. Functional defect.
Reason of defects: 1. Excipient/formulation variables.
2. Tablet process.
3. Tablet machine.
Common tableting problem
Capping (partial/complete separation of top/bottom crown of the tablet from the rest
of the body) & Lamination (separation of tablet into two or more layers)
Reasons:
1) Formulation:
Tableting materials has compression property.
Solution: Change the type of binder or binder concentration.
Insufficient amount of binder or improper binder.
Solution: Choose proper binder.
2) Tableting machine:
Worn& torn tooling (die, upper punch, lower punch)
Solution: Avoid damaged tooling set. |
Incorrect adjustment of punch level. 11
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Solution: Adjust the punch phases or level properly

Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

3) Tableting process: Over dry granulation.


Solution: Maintain proper moister in granulation.
Cracking (Appearance of small fine cracks on the upper and lower surface of the tablet)
& Chipping (It is the breaking of tablet edges while the tablet leaves the press or during
handling of tablets and coating process.)
Reason: Same as picking.
Picking (removal and addition of tableting material on a punch phase from the tablet
surface) & sticking (addition of tableting material to the die wall).
Reasons:
1) Formulation:
Use of low melting point materials.
Solution: Avoid low melting point excipient.
Inadequate and insufficient use of lubricant or anti-adherent.
Solution: Use correct type and amount of lubricant & anti-adherent.
Improper type or concentration of binder.
Solution: Use correct type/concentration of binder.
2) Tableting process: Under drying of granules having excessive moisture.
Solution: Properly dry the granules to control moisture content.
3) Tableting machine: Worn & torn tooling set.
Solution: Avoid damaged tooling set.
Mottling: It is the unequal color distribution on a tablet surface.
Reasons:
1) Formulation: Color of drugs differ from color of excipient.
Solution: By using same types of color in both drug & excipient.
2) Tablet process:
Imhomologous mixing of colorants.
Solution: Properly mix the colorants by using appropriate machine.
Surface migration of colorants during drying of granules.
Solution: Change drying condition such as temperature, drying rate etc.
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Particle size of colorant is relatively larger.
Solution: Use fine particle size. 12
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Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Weight variation: This is associated with under or over filling of the dye cavity during
tablet production. Over weight is responsible for toxicity.
Reason:
1) Formulation: Improper amount of gradient.
Solution: Use adequate gradient/sufficient gradient.
2) Tableting process: Poor mixing of gradient/lubricant.
Solution: Ensure optimum mixing of gradient or lubricant.
3) Tableting machine:
Length variation of lower punches.
Solution: Replace damaged punch.
Instrument parts are not properly cleaned.
Solution: Clean all parts properly.
Improper setting of instrument.
Solution: Instrument should be set up properly.

Hardness variation: Hardness variation is an indicator of the mechanical strength of


tablet. It will cause production of tablets which are too hard/soft.
Reason:
1) Formulation: Under or over concentration of binder.
Solution: Use optimum binder concentration.
2) Tableting Process: Under or over drying causing too much or too little moisture in
the granules.
Solution: Maintain proper moisture content of granules.
3) Tableting machine:
Application of too little or too little compression force.
Solution: Adjust optimum compression force.
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Under filed or over filled die cavity.
Solution: Maintain proper fill of die cavity. 13
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Md. Asif Hasan Niloy


5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Double impression: It is the occurrence of too impression or too imprint on the upper
or lower surface of the tablet.
Reason:
1) Tableting machine: Free rotation and uncontrolled traveling of the lower punch
between compression and ejection.
Solution: Proper controlling of punches. Especially lower punch.

Tests
1) Concentration variation test.
2) Content uniformity test.
3) Hardness test.
4) Friability test.
5) Disintegration test.
6) Dissolution test.
7) Appearance
8) Size and Shape (diameter/thickness).
9) Organoleptic properties (color, odor)
10) Assay or potency.
11) Presence of impurity.

Tablet Evolution test


Appearance: Visual Defect of Aspirin
Aspirin is a prodrug and it converted to salicylic acid and autic acid.
Odor/Smell
The diameter and thickness should be maintain in rang during packaging.
Diameter = Value of main scale + Vernier scale value 0.5 (Vernier constant)
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Related to the production which is called unofficial test.
(+) Deviation = (Max value-Average value)/(Average thick or diameter) 100 14
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(-) Deviation = (Min value-Average value)/(Average thick or diameter) 100
Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Weight variation test


It is done to ensure correct dose administration of the drug. It helps in production.
It is done in process quality control (IPQC)
At first 20 tablets are taken and individual weight of these tablets are measured.
Then average tablet weight are measured.
Official test
BP: Tablet weight 80mg or less 10% variation or deviation allow.
More than 80mg or less than 250mg 7.5% variation or deviation allow.
250mg or more 5% variation/deviation allow.
USP: Tablet weight 100 or 30mg or less 10% deviation allow.
More than 130 to 324mg
More than 324mg 5% variation.

Content uniformly
Used to check the weight of the tablet.
If API amount is less than 40mg apply correct dose test. It is applicable for low dose
tablets.
At first take 30 tablets and assayed for result.
85 to 115% is the acceptable range.

Hardness Test
Used to check
Hardness test machines:
Monsanto Hardness taster.
Pfizer Hardness taster.
Exceptable limit: In industry pressure is measured in kg.
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Oral tablets: 1 to 10kg
Chewable tablets: 3kg 15
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Sustain release tablets: 10 to 20kg.
Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Friability Test
Used to ensure that tablets do not break up during production and subsequent process
packaging like-packaging, transportation.
Friability test machines: Friabilator (Roche Company)
At first take 10 tablets and then weighted out.
Then take place in the machine to rotate the tablets for 100 times.
This machine rotate 25 times per minute.
Again weighted out the tablets. And finally
% of weight loss = (Initial weight -Final weight)/(Initial weight) 100
Normal range: Loss amount is not more than 1%

Disintegration Test
Used to measure the time requires to break down into granules.
Take 6 tablets and allow to pass through the machine. And calculate the time
requires to break down of the tablets.
Temperature: Requires 37
29 to 32 movements per minute.
Sieve size is 2 tp 2 0.2 mm
Required medium like water, phosphate buffer.
For uncoated tablets: - For film-coated tablets: -
Time: 15 minutes Time: 30 minutes
Media: H2O Media: H2O or 0.1M HCl
For sugar-coated tablets: -
Time: 60 minutes
Media: H2O or 0.1M HCl
For effervescing tablets: -
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5minutes in beaker contains 200ml of water at room temp.
For enteric coated tablets: - 16
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First 2hours in 0.1M HCl and then 3 hours in phosphate buffers (pH 6.8)
Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy
Tablet
Course Instructor: MD.SELIM HOSSAIN

Dissolution Test
Used to check the rate at which granules goes to solution form.
Machines:
USP dissolution apparatus I called Basket method.
Used for capsules.
USP dissolution apparatus II called Paddle method.
Used for tablets.
Reasons: Manufacturing process.
Type of dosage form.
Nature and amount of excipients.
Medium of dissolution: It varies with the drug types.
Water: 6.5/7.2 phosphate
Buffer: 0.1M HCl
Temperature: 37
Rotation Speed: It varies with the drug types. The normal range is 25rpm, 50rpm, 75rpm,
100rpm. And 75% should be dissolved in 45 minutes.
After going to solution form (10minutes) 5ml of the sample solution was separated and
then 5ml medium was added to the solution to maintaining balance.
The 5ml was taken to the UV spectroscopy or other spectroscopy to find out the
absorbance and calculate the dissolution rate.
After 1 hour the solution which was achieved may consider as 100% and then the
dissolution rate of the solution which is taken after 10 minutes is calculated.
Potency 96%
Overage 3%
Label claim 500mg
Batch size 100000
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Amount of drug = kg
1000 1000
500 100000 (100+3)
17
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96 1000 1000
kg
Md. Asif Hasan Niloy
5th Semester 24 BATCH
Industrial Pharmacy