Tablets

(Part II)

May Saab
Assistant Professor
Pharmaceutical Technology Department
Faculty of Pharmacy, BAU
 Methods of manufacturing of
compressed tablets
1. Wet granulation technique
2. Dry granulation technique
3. Direct compression
 1. Wet granulation technique
➢ It depends on the transformation of powders into granules of
good flow properties and good compressibility
 Advantages of wet granulation technique

➢ Ensure good flowability and compression

➢ Small dose drugs could be dissolved in binder solution to
ensure good distribution
➢ No dust production as in other techniques
 Limitations of wet granulation technique

➢ Not suitable for drugs sensitive to heat and moisture

➢ Dyes used may produce non-uniform color distribution
(mottling)
➢ Time consuming
➢ Expensive as it requires many equipment.
 1. Dry granulation technique
➢ It is also called pre-compression or double compression
technique.

STEPS OF DRY GRANULATION METHOD

 2. Dry granulation technique

Pre-compression can be done by 2 methods:

Slugging process Pressure roll process

 2. Dry granulation technique

➢ It can be used for large dose drugs to improve flow

properties and compressibility
➢ It is used for drugs sensitive to heat and moisture
(i.e. Conventional aspirin tablets)
➢ Lower cost than wet granulation
 3. Direct compression

➢ It is the process by which the mixture of drug and excipients

is directly compressed without any preliminary treatment.
➢ It is the simplest and the most economic method
➢ The mixture to be compressed must have:
• good flowability
• Cohere under pressure
• Good lubricating properties
➢ Tablets can be compressed by adding directly compressible
fillers that should be inert and of good flow (examples:
Microcrystalline cellulose, anhydrous and spray dried
lactose).
 3. Direct compression

➢ Advantages:
• Simple
• Time saving
• Few equipment used
➢ Disadvantages:
• Not applicable for large doses drugs with poor flowability and
compressibility
• Drugs and excipients should have approximately the same particle
size and density to avoid segregation and ensure uniform drug
distribution
 Types of compressed tablets
➢ They are classified according to their method of use into:
1. Chewable tablets
2. Tablets placed in the mouth
a. Sublingual tablets
b. Buccal tablets
c. Lozenges tablets
3. Tablets used to prepare solution or dispersion
a. Solution tablets
b. Dispersible tablets
c. Effervescent tablets
4. Swallowed tablets
a. Conventional tablets
b. Multilayer tablets
c. Coated tablets
 1. Chewable tablets
➢ They are designed to be broken rapidly in the
buccal cavity by the action of teeth.
➢ The taste is an important consideration
➢ Mannitol is the diluent of choice. Due to negative
heat of solution, it produces a cooling sensation in
the mouth and mask unpleasant taste
➢ A flavoring is also frequently included
➢ No disintegrant is needed
➢ Examples:
• Antacids (aluminium hydroxide..)
• Vitamins (for children and elderly)
 2. Tablets placed in the mouth

a. Sublingual b. Buccal c. Lozenges

 2. Tablets placed in the mouth
a. Sublingual tablets
small
Placed under the tongue
Rapid disintegration time
and dissolution
Mannitol is the diluent of
choice
Example: Nitroglycerin or
glyceryl trinitrate (0.3 mg)
Include disintegrant or
superdisintegrant
Flavors and sweeteners
may be added
b. Buccal tablets c. Lozenges
small Relatively large
Placed between cheeck, Placed in the mouth
lip and gum (buccal
pouch)
Dissolve slowly in the Dissolve or erode slowly in the
mouth (4 h) mouth (10-15 min)
Lactose is used as diluent Sucrose, mannitol, sorbitol are
used as diluent
Example: methyl Example: antibacterial agents,
testosterone (10 mg) anesthetics that produce local
effect in the mouth
No disintegrant is used No disintegrant
Not preferred Flavors and sweeteners may be
added
 3. Tablets used to prepare solution
or dispersion
a. Solution Tablets:
• These are formulated to dissolve completely in cold
water
• All ingredients must be freely soluble in water
b. Dispersible tablets:
• These are formulated to disintegrate rapidly in cold
water to produce suspension
• There is no need for all ingredients to be water soluble
c. Effervescent tablets:
• These tablets effervesce (CO2) when added to cold
water
• Rapid disintegration and increased palatability
• Stored at relative humidity 25% and at 25° C
• Hydrophilic lubricant is usually used (SLS, PEG)
 4. Swallowed Tablets
a. Conventional tablets (uncoated)

b. Multilayer tablets:
• They are composed of 2 or 3 layers
that are compressed together.
• They are used to separate 2
incompatible drugs (e.g. aspirin and
phenylpropanolamine)
• They may also be used for sustained
release tablets consisting of 2 layers
(one for immediate release and the
other for release of maintenance
dose)
c. Coated tablets
 c. Coated Tablets

➢ Tablets may be coated after compression for several

reasons:
1. To protect the tablet from environmental factors
(light, humidity..)
2. To mask unpleasant taste
3. To aid product identification
4. To provide a mean of controlled drug release
 Types of coating

1. Sugar coating
2. Film coating
3. Compression coating
 1. Sugar coating

➢ It is the oldest method of coating

➢ It is carried out in a coating pan
➢ The core to be coated should be:
• Of optimum convexity for uniform coating
• Hard and non friable
• Of good disintegration and dissolution
 1. Sugar coating

➢ Steps involved in sugar coating are:

1. Sealing
2. Sub-coating
3. Smoothing and coloring
4. Polishing
5. Printing
 a. Sealing

➢ Sealing protects tablet core from shock as it renders the tablet

core stronger.
➢ Sealing also protects tablet core from moisture which may
initiate disintegration and affect stability of sensitive drugs
➢ Sealing is carried out using alcoholic solution of polymers such
as cellulose acetate phthalate, polyvinyl acetate phthalate or
shellac.
➢ Little talc is added to prevent adhesion of tablets together
 b. Sub-coating
➢ This stage produces rounded shape tablets free from sharp
edges
➢ The sub-coat represents 50-100 % of the core thickness
➢ Gum solution (e.g. acacia) is applied followed by dusting with
dry powder (talc, CaCO3..)
➢ The process is repeated until the required shape is obtained

c. Smoothing and rounding

➢ Several layers of syrup are applied
➢ Syrup may contain Titanium dioxide to render the tablet
opaque
 d. Colouring
➢ Tablets are treated with syrup containing the desired coloring
agents (water soluble colors)

e. Polishing
➢ This step is carried out in a polishing pan, using a mixture of
waxes (beeswax, carnuba wax)

f. Printing
➢ Identification code, company name or brand name of the
tablet is printed using pharmaceutical grades of ink
 2. Film coating

➢ It is the formation of thin

uniform film surrounding the
surface of tablet core
➢ Advantages:
• 2-3 % weight increase
• Less expensive and time saving
• No adverse effect on
disintegration step as there is no
need for sealing step
 2. Film coating

➢ Film forming materials:

a. Polymers:
• Polymers may be dissolved or dispersed in a solvent (water, alcohol..)
• Should produce a continuous film
• Should dissolve in GIT fluids (in acids or alkaline pH)
• Examples: Hydroxypropylmethyl cellulose (HPMC), Hydroxypropyl
cellulose (HPC), Methyl cellulose (MC), Eudragits or acrylates (used in
solution or suspensions)
 2. Film coating

➢ Film forming materials:

b. Plastisizers:
• They are added to increase the flexibility of the film, facilitating the
adhesion of the film on the core (e.g. glycerin, propylene glycol or
castor oil)
c. Coloring agents:
• They are either water soluble or water insoluble (lakes)
• Lakes are generally more preferred as they are stable against light while
water soluble dyes may fade.
 3. Enteric coating

➢ This is a special type of film coating

➢ The coat should remain intact in the stomach but dissolve in the
small intestine
➢ Enteric coated tablets are used in the following cases:
• If the drug is destroyed by the acidic pH in the stomach (e.g.
erythromycin)
• To protect the gastric mucosa from the irritating effect of certain drugs
(e.g. aspirin, salicylates)
➢ Polymers should be insoluble in water and acid solution of pH 1-
4 (e.g. CAP, PVAP, HPMCP).
➢ Plasticizers include diethyl phthalate and dimethyl phthalate.
 4. Compression coating

➢ Compression coating is a dry process

which involves the compaction of
granular materials around preformed
tablets core using specially designed
tableting equipment.
➢ It is used to:
• separate two incompatible drugs
• Prepare sustained release tablets with
the fast release drug in the coat and the
sustained release drug in the core
 Evaluation of compressed tablets
(Quality control Test )
➢ During formulation development and during tablet
manufacturing, a number of quality control tests are performed
to ensure that tablets produced meet the requirements as
specified in official compendium and conventional
requirements established by the industries over the years
(registration file).
➢ These tests can be grouped into two broad categories :
1. Pharmacopoeial or Official tests
2. Non-pharmacopoeial or Non-official tests
 1. Pharmacopeial or Official tests
➢ They are called official tests because the test methods are
described in official compendia such as the British
Pharmacopoeia, American Pharmacopoeias etc. They are
standardized test procedures which have clearly stated limits
under which tablets could be accepted.
➢ These tests include:
a. Content of Active Ingredient/ Absolute drug content test
b. Uniformity of Weight
c. Uniformity of Content
d. Disintegration time test
e. Dissolution test
➢ These tests are traditionally concerned with the content and
the in vitro release (reflect in-vivo) of the active ingredient.
 a. Content of Active Ingredient

➢ Twenty tablets should be randomly selected from a

batch of tablets. The tablets are weighed together and
are crushed in a mortar with a pestle.
➢ An amount equivalent to the theoretical content of each
tablet is weighed and drug content is analyzed.
➢ The assay procedures are usually given in the individual
drug monograph.
 b. Uniformity of Weight/ Weight variation test

➢ The test for uniformity of weight is performed by weighing

individually 20 tablets randomly selected from a tablet batch
and determining their individual weights. The individual
weights are compared with the average weight.
➢ The sample complies with USP standard if no more than 2
tablets are outside the percentage limit and if no tablet differs
by more than 2 times the percentage limit.
 c. Uniformity of Content

➢ According to USP method, 30 tablets are randomly selected, 10 of

these tablets are assayed individually according to the method
described in the individual monograph.
➢ The amount of active ingredient in 9 of 10 tablets must be within
the range of 85% to 115% of the label claim, and no tablet should
exceed ± 25% (75%-125%) of the labelled drug content.
➢ If not more than one tablet exceeds the ± 15% limit , the
remaining 20 tablets are assayed individually and none should fall
outside of the 85% to 115% range for the batch to be accepted.
 d. Disintegration Time Test

➢ This test is conducted using Erweka-disintegration

tester.
➢ The apparatus consists of a basket-rack assembly
containing six open-ended transparent tubes, held
vertically upon a 10-mesh stainless steel wire
screen.
➢ During testing, a tablet is placed in each of the six
tubes of the basket, and through the use of a
mechanical device, the basket is raised and
lowered at 28 to 32 cycles per minute in a bath of
fluid at 37o C(e.g. water).
➢ Tablets are said to have disintegrated if no
fragments remains on the screen, or if residues
remain, it should be a soft mass
 d. Disintegration Time Test

➢ Accepted average disintegration time:

• Uncoated conventional tablet: 15-30 minutes
• Buccal tablet: ̴ 4 hours
• Sublingual tablet: very short time
• Enteric coated tablet: tested for 1 hour in simulate gastric fluid without
disintegration, and disintegration time in simulated intestinal fluid as
specified in the pharmacopeia
 e. Dissolution Test

➢ In vitro dissolution test is performed

using Erweka dissolution rate tester.
➢ The flask is filled with the specified
volume of the dissolution medium (37 ±
0.5 oC)
➢ The motor is adjusted to rotate at the
specified speed.
➢ The test is carried out on 6 tablets (each
in a flask).
➢ Samples (filtered) are removed from the
dissolution chamber at periodic intervals
and analyzed for drug content.
➢ Plot the % drug dissolved against time
 e. Dissolution Test

➢ Tablets should meet the requirements (e.g. 70% dissolution

within 45 minutes.
➢ If 1 or 2 tablets fail to meet the requirements, the test is to be
repeated with 6 more tablets.
➢ Not less than 10 out of 12 tablets should meet the
requirements.
2. Non-Pharmacopeial or Non-Official Tests
➢ These are tests that are performed on tablets and which are
not listed in official compendia and concern a variety of
quality attributes that need to be evaluated.
➢ Some of these tests have no officially set limits for acceptance
or rejection and thus may vary from manufacturer to
manufacturer and from formulation to formulation.
➢ Non-official tests include:
a. hardness or crushing strength test.
b. friability test.
c. thickness test etc.
 a. Tablet Hardness or Crushing Strength Test

➢ This test measures the degree of force

(in kilograms or pounds) needed to
fracture a tablet.
➢ The crushing strength of tablets is
usually checked using Monsanto-Stokes
hardness tester or Erweka hardness
tester
➢ A force of 4-8 Kg/cm2 is considered the
standard range for a satisfactory tablet
(conventional).
➢ Measurement is usually carried out using
a minimum of six tablets.
 b. Friability Test

➢ The test is carried out using “Roche

Friabilator”, to mimic the forces caused by
phenomena such as collisions and sliding of
tablets towards each other, which a tablet
is subjected to during coating, packaging,
handling, and shipping.
➢ A minimum of 20 tablets are brushed to
remove surface powder, weighed and
subjected to rotating motion in a drum (25
revolution/min) for 4 minutes. They are
then brushed again and reweighed.
 b. Friability Test

➢ The measure of abrasion/ friability loss is usually expressed

as percentage loss in weight as follows:

➢ The test is rejected if any tablet caps, laminates or breaks up.

➢ As a rule of thumb, a maximum weight loss of not more than
1% generally is considered acceptable for most
pharmaceutical products.
 c. Tablet Thickness

➢ Tablet thickness is determined by the

amount of fill permitted to enter the die
cavity, the compaction characteristics of
the fill material, and the force or pressure
applied during compression.
➢ Tablet thickness is measured with a vernier
caliper, or micrometer screw gauge or
automated equipment.
➢ The thickness of a tablet should be
controlled within ±5% variation of a
standard value depending on the size of
the tablet.