UNIT-III

CAPSULES

1. DEFINITION OF CAPSULE
Capsules are the solid dosage form in which one or more medicaments are enclosed in a
water-soluble bio-degradable shell made up of gelatin.

2. ADVANTAGESOF CAPSULES
i. Capsules are tasteless, odourless and can be easily administered (orally).
ii. They are attractive in appearance.
iii. Suitable for substances having bitter taste and unpleasant odour.
iv. Combination of powder drugs can be used.
v. They can be filled quickly and conveniently.
vi. They are easy to handle and carry.
vii. They are economical.

3. DISADVANTAGESOF CAPSULES
i. Not suitable for highly soluble substances like potassium chloride,
potassium bromide, etc.
ii. Not suitable for highly efflorescent or deliquescent materials.
iii. Special conditions are required for storage.

4. GELATIN
• Gelatin is heterogeneous product derived from animal’s collagen.
• The sources of gelatin include animal bone, frozen calf skin and pork skin.
• Types of gelatin-
a) Type A: derived from pork skin by acid treatment
b) Type B: derived from bones and animal skin by alkaline process

5. TYPES OF CAPSULES
• There are two types of capsules:-
a) Hard- gelatin capsules (Hard- shelled capsules/Dry Filled Capsules)
b) Soft- gelatin capsules (Soft- shelled capsules/Softgels)
a) Hard-Gelatin Capsules
➢ These are used for administration of solid medicaments.
➢ Hard-gelatin capsules are typically made using gelatin.
➢ It consists of two parts-
a) Body- lower diameter that is filled
b) Cap-higher diameter seal
➢ Example of hard-gelatin capsule: Omeprazole capsule, Chitosan capsule, etc.
➢ Capsule size
• For human use, empty capsules ranges in size from 000 to 5.
• The largest size of the capsule is no. ‘000’ and smallest number is no. ‘5’
• The standard shape of capsules is Symmetrical Bullet shape.
• Generally, hard gelatin capsule are used to encapsulate between 65mg to 1gm drugs.
Capsule number Capacity (mg)
000 950 apx. (1gm)
00 650
0 450
1 300
2 250
3 200
4 150
5 100

➢ Components of hard-gelatin capsules: The main components of capsule are-

• Gelatin, certified dyes, sugar, water (12-16%), sulfurdioxide (0.15%) – prevent
decomposition during manufacture and opaquants-titanium dioxide.
➢ Manufacturing of capsules: Steps involved in making of empty gelatin capsule shells are-
• Dipping: Pairs of stainless steel pins are dipped into dipping solution (temp. 500C) to
form caps and body.
• Spinning: Pins are rotated to distribute gelatin over the pin uniformly.
• Drying: Gelatin is dried by cool air to form hard shells.
• Stripping: Series of bronze jaws strip the cap and body of capsules from pins.
• Trimming and joining: Stripped cap and body are trimmed to required length and joined
and ejected from machine.
• Polishing: Acela-cota pan is used to dust and polish.
➢ Filling of Capsule
• Capsule filling can be done by following methods:
i. Hand Operated method
▪ The commonly known hand operated machine is Feton Capsule Filling Machine.
▪ It consists of:
 A bed and loading tray having 200-300 holes each, a powder tray, a pin plate having a
rubber top, a lever and a cam handle.

The empty capsules are filled in the loading tray which is placed over loading bed. The
cam handle is operated to separate capsule caps from their bodies. The powder tray is
placed and filled with proper amount of powder. The pin plate is lowered and the filled
powder is pressed by moving pin downward. Powder tray is remover after filling and cap
holding tray is placed again. Plate with rubber top is lowered and the lever is operated to
lock cap and body. Loading tray is removed and filled capsule are collected.

ii. Semi-Automatic devices

iii. Automatic filling machine
Ex. Osaka capsule filling machine, macofar capsule filling machine, etc.

b) Soft-Gelatin Capsules
➢ Soft-gelatin capsules are oblong, spherical, tube and oval in shape.
➢ These are primarily used for oils and for active ingredients that are dissolved or suspended in
oil.
➢ These capsules consist of a continuous gelatin shell surrounding a liquid core.
➢ Soft-gelatin capsule shells are a combination of gelatin, water, opacifier and a plasticizer
(such as glycerin) and sorbitol.
➢ The inner fill material consists of Oily liquids, Solution fills (Active dissolved in a carrier) or
Suspension fills (Active dispersed in a carrier).
➢ Example of soft-gelatin capsules are: Deep sea fish oil, etc.
➢ Soft Gelatin Encapsulation Processes and Equipment
a) Rotary Die process:
• Two ribbons of gelatin are fed continuously into a rotating die assembly to form the two
halves of a capsule. The ribbons converge adjacent to a fill injector. The fill injector is
actuated by a pump which measures and dispenses the appropriate volume of fill material
 into the capsules. The filled capsules are subsequently sealed as the die assembly rotates.
Pump heads are available for fill weights as low as 100 mg. For oral dosage forms, the
fill weight ranges from 100 mg up to about 1 gram.
• After encapsulation, the capsules undergo drying in a tumble drying tunnel. From the
drying tunnel, the capsules are transferred into a low humidity drying room (equilibrium
moisture content in the range of 6 - 8%).
• After drying, the softgels are sorted (sized), polished, printed, and inspected for their
quality.

b) Plate process:
• In this process a warmed sheet of gelatin sheet is placed over a die plate having a number
of depression or moulds or die pockets by applying vacuum. A measured quantity of
liquid medicament is pour over it and another plate of the mould is placed over it and the
pressure is then applied to the combine plate. The capsules are then simultaneously
shaped, filled, sealed and cut into individual units. This method is uses for small scale
preparation of soft gelatin capsules. It has 20-40% of net moisture content.
➢ Difference between hard and soft gelatin capsule

6. IN-PROCESS QUALITY CONTROL TESTS FOR CAPSULE

➢ In-process quality control tests for capsule drug products are carried out at predefined
intervals during the product manufacturing.
➢ During the encapsulation of soft gelatin capsules, the following parameters are usually
closely monitored and controlled:
• Gel ribbon thickness and uniformity across the ribbon
• Softgels seal thickness at the time of encapsulation
• Weight of the capsule fill and its variation from capsule-to-capsule
• Weight of the capsule shell and its variation from capsule-to-capsule
• Moisture level of the capsule shell before and after drying

7. FINISHED PRODUCT QUALITY CONTROL TESTS FOR CAPSULES

➢ Finished capsules are evaluated by the following tests:
i. Permeability and sealing
• Soft gelatin capsules are tested for absence of leakage by visual inspection. Similarly,
hard gelatin capsules are tested for any breakage or opened cap and body.

ii. Potency and impurity content

• All capsules are tested for drug content (potency, as a per cent of label claim). In
addition, most drug products are tested for related substances or impurities. These must
meet predefined specifications for a batch to be acceptable.

iii. Weight variation test for hard gelatin capsules

• Ten capsules are usually weighed individually and the contents are removed. The emptied
shells are individually weighed and the net weight of the contents is calculated by
subtracting the weight of the shell from the respective gross weight. The content of active
ingredient in each capsule may be determined by calculation based on the per cent drug
content in the formulation.
 iv. Disintegration time test for capsules
• Disintegration of hard and soft gelatin capsules is evaluated to ensure that the drug
substance is fully available for dissolution and absorption from the gastrointestinal tract.
• The capsules are placed in the basket-rack assembly, which is repeatedly lowered 30
times per minute into a thermostatically controlled bath of fluid at 37 ± 2 ˚C and observed
over the time described in the individual monograph.

v. Dissolution test for capsules

• Drug absorption and physiological availability depend on the drug substance being in the
dissolved state at the site of drug absorption.
• The compendial dissolution test for capsules uses the same apparatus, dissolution
medium, and test as that for uncoated and plain coated tablets.

vi. Stability testing of capsules

• Stability testing of capsules is performed to determine the physicochemical stability of
the drug substance in the finished drug product under specified package and
recommended storage conditions intrinsic stability of the active drug molecule and the
influence of environmental factors (e.g., temperature, humidity, light), on formulation
components, and the container and closure system.

8. HANDLING AND STORAGE OF CAPSULE

• Capsules should be packed in a well-closed glass or plastic containers and stored in a cool
place.
• The recommended storage conditions for empty capsule shells of hard gelatin are 15 to 25°C
and a relative humidity of between 35% and 65%. This condition is designed to minimize
moisture absorption or loss, and the resultant changes in physical dimensions, during the
encapsulation operation.
• The recommended storage temperature for prepared soft gelatin capsules are 20-240C.
• To prevent capsules from rattling, tuft cotton is placed over and under the capsules in vial.
• In vials containing very hygroscopic capsules, packet-containing desiccants likes silica gel or
anhydrous calcium chloride may be placed to prevent moisture absorption by capsules.
• Now a days, capsules are strip packed which provide sanitary handling of medicines, ease in
counting and identificton.
9. APPLICATIONOF CAPSULE