Theory

Granulation
Granules are agglomerates of powdered materials prepared into larger,
free
flowing particles. They typically fall within the range of 850 μm (No. 20 sieve) to
4.75
mm (No. 4 sieve) size. The shape of granules is generally irregular.
Granules are usually made as a step to prepare tablets. Granules flow into the
dies
more evenly and more freely than particles from the hopper (the funnel-like
container
holding the drug to guide its flow into the tableting press). Advantages of
granules are
listed below:
1. Granules shows good flow properties. The easy flow characteristics are
important in
supplying drug materials from the hopper or feeding container into the
tableting
presses. For this reason powder mixtures are usually granulated if they are
intended to
be compressed into tablets. Granules also eliminate or control dust.
2. Granules increase compressibility.
3. Granules have smaller surface area than a comparable volume of
powders. This
makes granules more stable physically and chemically than the
corresponding
powders. Granules are less likely to cake or harden upon standing than are
powders.
4. Granules are more easily wetted by a solvent than are certain
powders, so that
granules are also preferred in making solutions.
5. Granules produce particle-size uniformity, thus content uniformity.
6. Granules prevent segregation of constituents of powder mixture.

Wet Granulation
The most widely used process of agglomeration in pharmaceutical industry is
wet
granulation. Wet granulation process simply involves wet massing of the powder
blend
with a granulating liquid, wet sizing and drying.
Important steps involved in the wet granulation
1. Mixing of the drug(s) and excipients
2. Preparation of binder solution
3. Mixing of binder solution with powder mixture to form wet mass screens.
4. Coarse screening of wet mass using a suitable sieve (6-12)
5. Drying of moist granules 
6. Screening of dry granules through a suitable sieve (14-20)
7. Mixing of screened granules with disintegrant, glidant, and lubricant.
Limitation of wet granulation
1. The greatest disadvantage of wet granulation is its cost. It is an expensive
process
because of labor, time, equipment, energy and space requirements.
2. Loss of material during various stages of processing
3. Stability may be major concern for moisture sensitive or thermo labile
drugs
4. Multiple processing steps add complexity and make validation and
control
difficult
5. An inherent limitation of wet granulation is that any incompatibility
between
formulation components is aggravated.
Principle
Paracetamol is widely used as non-steroidal analgesic and antipyretic drug. The
adult dose of paracetamol is 500 mg three times a day. The dose of drug is
500 mg
diluent is not required in the formulation. Magnesium stearate and talc is
used as
lubricant and glidant respectively.
Wet granulation methodology is widely used for preparation of paracetamol
granules/tablets. For the granulation, paracetamol and starch powder is
mixed and
granulated with starch paste (binder). Granulating Starch powder will be
used to
disintegrate granules.

1. Concept of granulation
2. Preparation of starch paste
Requirements
Chemicals: Paracetamol IP, starch, magnesium stearate, talc, methyl paraben
Glasswares: Measuring cylinder, beaker, mortar and pestle, granulating sieve,
etc.
Formula
Granulation
Sr. No. Ingredients Quantity given Quantity taken

Use
1 Paracetamol IP 500 mg 10 g Antipyretic
2 Starch Paste 10 % qs

5 ml (0.5g) Binder
3 Starch Powder 12.5 mg 0.25 g Disintegration

Post granulation
Sr. No. Ingredients Quantity given Quantity taken Use
1 Granules ~10 g -
2 Starch powder 5 % Disintegration
3 Magnesium stearate 5 % Lubricant
4 Talc 1 % Glidant
5 Methyl paraben 0.1 % Preservative

Procedure
1. Weigh and pass paracetamol powder through 100# sieve.
2. Mix paracetamol and starch powder uniformly in mortar and pestle.
3. Prepare 10 % starch paste in boiling water and stir until it becomes
translucent.
4. Add starch paste dropwise in mortar to get cohesive mass. Record
quantity of
starch paste used for granulation.
5. Screen prepared cohesive mass through 12# granulating sieve and collect
it on
granulating tray.
6. Dry granules in tray at 50oC for 30 min. Pass 50 % dried granules through
16#
sieve to get uniform particle size and continue drying for 30 min.
7. Using 22/44 # sieve separate granules and fine particles. Material on 22#
sieve is
final granules and on 44# sieve is fines. Record the weight of final granules and
fines.
8. If the quantity of fines is more than 10% of final granules then recycle the
fines.
9. Finally take the weight of granules and blend granules with remaining
ingredients
in a polybag.
10. Store prepared granules in well closed and labelled container till evaluation.
Storage: Store in well closed container in cool and dry place.
Calculations:
1. Starch Paste
Qty of starch powder in grams = 10 x volume of starch paste used / 100 g
2. Theoretical yield [TW]
TW = Sum of weights of all ingredients in granulation
3. Practical yield
Practical yield = weight of final granules
4. Percent yield
Percent yield= Practical yield x 100 / Theoretical yield
5. Percent loss
Percent loss = 100 – Percent yield
Result
Theoretical yield _________
Practical yield _________
Percent yield _________
Percent loss _________
Conclusion
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2. Scribd presentation
3. AI
Aim 2 – to perform various evaluation parameters of given
marketed tablet.
Reference: Lachman L, Lieberman HA, Kanig JL. The Theory and Practice of Industrial
Pharmacy. 3rd ed. Mumbai: Varghese Publishing House; 1987.
Requirements

Apparatus:

 Weighing balance
 Monsanto or Pfizer Hardness Tester
 Roche Friabilator
 Disintegration Test Apparatus
 Beakers, Stopwatch, Forceps

Materials:

 20 Paracetamol Tablets (500 mg)

 Distilled Water

Theory

The evaluation of tablets is a critical quality control (QC) process in the pharmaceutical
industry to ensure that each batch of tablets meets the established standards of quality, safety,
and efficacy. These tests are designed to check various physical and mechanical properties of
the tablet. The results determine whether the batch can be approved for release.

The key evaluation parameters are:

1. Weight Variation: This test ensures that each tablet contains the correct amount of
drug, thereby guaranteeing dose uniformity. Variations in weight can lead to under-
dosing or over-dosing.
2. Hardness (Crushing Strength): This measures the mechanical strength of the tablet.
The tablet must be hard enough to withstand the rigors of handling, packaging, and
transportation, but not so hard that it fails to disintegrate properly.
3. Friability: This test measures the tablet's ability to resist abrasion and chipping. It
complements the hardness test and indicates the tablet's durability. High friability
results in weight loss and unacceptable tablets.
4. Disintegration Test: This test measures the time required for a tablet to break down
into smaller particles when placed in a liquid medium under specified conditions. It is
a crucial indicator of the drug's availability for absorption in the body.

Procedure

1. Weight Variation Test

1. Select 20 tablets at random from the sample.

2. Weigh each tablet individually using a digital weighing balance.
3. Calculate the average weight of the 20 tablets.
4. Compare the individual weight of each tablet with the average weight and calculate
the percentage deviation.
5. Check if the deviations fall within the pharmacopoeial limits.

2. Hardness Test
 1. Select 6 tablets at random.
2. Place a tablet in the hardness tester between the jaws.
3. Adjust the knob until the tablet breaks and note the pressure required, which is
indicated on the scale.
4. Repeat the process for all 6 tablets.
5. Calculate the average hardness.

3. Friability Test

1. Select 10 tablets and weigh them accurately (this is the initial weight, W₁).
2. Place the tablets in the drum of the Roche Friabilator.
3. Operate the apparatus at 25 rpm for 4 minutes (100 revolutions).
4. Remove the tablets, carefully remove any loose dust (dedust), and weigh them again
(this is the final weight, W₂).
5. Calculate the percentage friability.

4. Disintegration Test

1. Place one tablet in each of the 6 tubes of the disintegration apparatus basket.
2. Place the basket in a beaker containing distilled water maintained at 37 ± 2°C.
3. Start the apparatus, which moves the basket up and down in the water.
4. Note the time taken for all 6 tablets to completely disintegrate (i.e., no solid residue
remains on the screen).

Observation

1. Weight Variation Test

 Average weight of 20 tablets = (Sum of weights of 20 tablets) / 20 = 10850 mg / 20 =

542.5 mg
 Pharmacopoeial Limit: For tablets with an average weight greater than 250 mg, the
% deviation should not be more than ±5% for any tablet.

Tablet No. Weight (mg) Deviation from Avg. (mg) % Deviation

1 540 -2.5 -0.46%
2 545 +2.5 +0.46%
3 542 -0.5 -0.09%
4 548 +5.5 +1.01%
5 539 -3.5 -0.64%
... (and so on for 20 tablets) ... ... ...
Total 10850

2. Hardness Test

 Average Hardness = (Sum of hardness values) / 6 = 30 kg/cm² / 6 = 5.0 kg/cm²

 Standard Limit: Typically 4-8 kg/cm² for uncoated tablets.

Tablet No. Hardness (kg/cm²)

1 5.2
2 4.8
3 5.0
4 5.3
5 4.7
6 5.0
Total 30.0

3. Friability Test

 Initial weight of 10 tablets (W₁) = 5.430 g

 Final weight of 10 tablets (W₂) = 5.405 g
 % Friability = [(W₁ - W₂) / W₁] × 100 = [(5.430 - 5.405) / 5.430] × 100 = 0.46%
 Pharmacopoeial Limit: Percentage friability should be less than 1%.

4. Disintegration Test

 Observed Disintegration Time: 6 minutes 30 seconds.

 Pharmacopoeial Limit: For uncoated Paracetamol tablets, the disintegration time
should not be more than 15 minutes.

Result

The given batch of marketed Paracetamol tablets was evaluated for various quality control
parameters.

Parameter Observed Value Pharmacopoeial Limit Result

Weight Variation All tablets within ±5% Not more than ±5% Pass
Hardness 5.0 kg/cm² 4-8 kg/cm² Pass
Friability 0.46% < 1% Pass
Disintegration Time 6 min 30 sec < 15 minutes Pass

All the evaluated parameters for the given tablets were found to be within the standard
pharmacopoeial limits. Therefore, the batch complies with the quality control standards.

Classification and Types of Tablets (According to Lachman & Lieberman)

Tablets can be classified into four major categories based on their route of administration and
function.

I. Tablets Ingested Orally

These are tablets designed to be swallowed, usually with a glass of water. This is the largest
and most common group.

 Standard Compressed Tablets: The most common type, manufactured by a single

compression of a drug with excipients. They are designed for immediate release of the
active ingredient.
 Multiple Compressed Tablets: Made by more than one compression cycle.
o Layered Tablets: Composed of two or more parallel layers of different
materials, compressed one on top of the other. This is used to separate
incompatible ingredients or to provide a modified-release profile.
o Compression-Coated Tablets (Dry-Coated Tablets): A tablet within a
tablet. An inner core is created, and then a layer of granulation is compressed
around it. This is useful for moisture-sensitive drugs or for creating complex
release patterns.
 Delayed-Release / Enteric-Coated Tablets: These have a coating that resists the
acidic environment of the stomach but dissolves in the less acidic small intestine. This
protects the drug from gastric acid, protects the stomach from irritating drugs, or
delivers the drug to a specific site.
 Sugar-Coated Tablets (SCT): Tablets coated with a colored or uncolored sugar
layer. The coating masks unpleasant tastes, protects the drug, and enhances
appearance.
 Film-Coated Tablets (FCT): Tablets coated with a thin, durable polymer film. This
offers the same benefits as sugar-coating but with less weight and size increase.
 Chewable Tablets: Designed to be chewed and disintegrated in the mouth before
swallowing. They are ideal for children and adults who have difficulty swallowing
conventional tablets.

II. Tablets Used in the Oral Cavity

These tablets are not swallowed but are used within the mouth for local or systemic effects.

 Buccal Tablets: Placed between the cheek and gum, where they dissolve slowly for
drug absorption through the buccal mucosa. This route avoids first-pass metabolism.
 Sublingual Tablets: Placed under the tongue. They dissolve rapidly, allowing for fast
absorption of the drug into the bloodstream for a quick onset of action.
 Troches and Lozenges: Designed to dissolve slowly in the mouth to provide a
continuous local effect in the throat or oral cavity.
 Dental Cones: Small tablets designed to be placed in an empty tooth socket after
extraction to prevent infection or reduce bleeding.

III. Tablets Administered by Other Routes

This category includes tablets not administered through the gastrointestinal tract.

 Implants (or Implantation Tablets): Small, sterile, solid masses designed for
subcutaneous implantation to provide a slow and continuous release of a drug over a
prolonged period.
 Vaginal Tablets (Vaginal Inserts): Uncoated, ovoid tablets inserted into the vagina
for a local effect, such as treating infections.
IV. Tablets Used to Prepare Solutions

These tablets are dissolved in water before administration or use.

 Effervescent Tablets: Uncoated tablets containing an acid and a

carbonate/bicarbonate. They react with water to produce CO2, causing rapid
disintegration and dissolution of the drug into a palatable, carbonated liquid.
 Dispensing Tablets (DT): No longer in common use, these were highly potent tablets
used by pharmacists to compound prescriptions. They were not to be dispensed
directly to patients.
 Hypodermic Tablets: Originally used by physicians to prepare solutions for
injection. They are now obsolete due to the need for sterility in injectable
preparations.
 Tablet Triturates: Small, molded or lightly compressed tablets that must be
completely and rapidly soluble in water.