EXPERIMENT - 1

AIM: - To evaluate the empty hard gelatin capsules.

REFRENCE: - British Pharmacoepia 2007, United States Pharmacoepia 2007,

L.Lachman, H.A. Lieberman, J.L. Kanig (1986). The Theory and Practice
of Industrial Pharmacy (3rd Ed.). Lea & Febiger, Philadelphia.

CATEGORY: - Pharmaceutical Aid

ODOUR: - Keep 100 capsule shells in a well-closed bottle for 24 hrs at a temperature
b/w 30-40C. The shell does not develop any forcing odour.

STORAGE: - Store in a well-closed container in a cool place.

LABELING-LABEL STATES: -

 Size of capsules
 Only permitted colors, if any
 Storage conditions

THEORY: -

Capsules are solid dosage forms in which the drug is enclosed within either a hard or soft
soluble container or “shell.”

Capsules are solid preparations with hard or soft shells of various shapes and capacities,
usually containing a single dose of active substance(s). They are intended for oral
administration. The shells are usually formed from gelatin; however, they also may be made
from starch or other suitable substances. Hard-shell capsule sizes range from No. 5, the
smallest, to No. 000, which is the largest, except for veterinary sizes.

The shell of hard gelatin capsules basically consists of gelatin, plasticizers and water. Modern
day shells may, in addition, consist of preservatives, colours, opacifying agents, flavours,
sugars, acids, enteric materials etc. The gelatin is marketed in a large number of varieties and
a specific quality and gelatin having specified gel strength, viscosity, iron content etc. should
be selected for capsules.

The capsules shells should be stored under controlled conditions of temperature and
humidity. The normal moisture content of shell is 10 to 15%. Under conditions of low
humidity they may soften and grow tacky.

The contents of capsules may be solid, liquid or of a paste-like consistency. They consist of
one or more active substances with or without excipients such as solvents, diluents,
lubricants and disintegrating agents. The contents do not cause deterioration of the shell. The
shell, however, is attacked by the digestive fluids and the contents are released.

Several categories of capsules may be distinguished:

Hard capsules; soft capsules; gastro-resistant capsules; modified-release capsules; cachets.
PROCEDURE: -

I. Identification Test for capsules: -

Boil one capsule shell with 25ml H2O, allow cooling & centrifuging. To 5ml of supernatant
liquid add 1ml of tannic acid solution; a precipitate is produced in each case.

II . Microbial Limits: -
This test is done to check any presence of microbes, specially Bacteria in the capsule shell.
Procedure:- Crush the Capsule and see the powder of shell under the microscope. Total
microbial count 1000g of capsule shells , 1.0g of capsules is free from E.Coli & Salmonella.

II I. Loss on Drying: -
This test is done to check the moisture loosing limit of capsule sheel when kept in extreme
conditions.
Procedure:-Between 12.5%& 16.0% determined on 1g of capsule shells by drying in an
oven for 4 hrs or to constant weight.

IV. Disintegration Test for Capsules: -

This test is provided to determine whether tablets or capsules disintegrate within the
prescribed time when placed in a liquid medium under the experimental conditions
presented below.

For the purposes of this test, disintegration does not imply complete dissolution of the unit or
even of its active constituent. Complete disintegration is defined as that state in which any
residue of the unit, except fragments of insoluble coating or capsule shell, remaining on the
screen of the test apparatus or adhering to the lower surface of the discs, if used, is a soft
mass having no palpably firm core.

Apparatus: The apparatus consists of a basket-rack assembly, a 1 litre, low-form beaker,

149 ± 11 mm in height and having an inside diameter of 106 ± 9 mm for the immersion fluid,
a thermostatic arrangement for heating the fluid between 35 °C and 39 °C, and a device for
raising and lowering the basket in the immersion fluid at a constant frequency rate between
29 and 32 cycles per minute, through a distance of 55 ± 2 mm. The time required for the
upward stroke is equal to the time required for the downward stroke, and the change in
stroke direction is a smooth transition, rather than an abrupt reversal of motion. The basket-
rack assembly moves vertically along its axis. There is no appreciable horizontal motion or
movement of the axis from the vertical. The assembly used is Basket-rack assembly The
basket-rack assembly consists of 6 open-ended transparent tubes, each 77.5 ± 2.5 mm long
and having an inside diameter of 21.85 ± 1.15 mm and a wall 1.9 ± 0.9 mm thick; the tubes
are held in a vertical position by 2 plates, each 90 ± 2 mm in diameter and 6.75 ± 1.75 mm in
thickness, with 6 holes, each 24 ± 2 mm in diameter, equidistant from the centre of the plate
and equally spaced from one another.

Procedure:-
Place 1 dosage unit in each of the 6 tubes of the basket and, if prescribed, add a disc. Operate
the apparatus using the specified medium, maintained at 37 ± 2 °C, as the immersion fluid.
At the end of the specified time, lift the basket from the fluid and observe the dosage units:

2
all of the dosage units have disintegrated completely. If 1 or 2 dosage units fail to
disintegrate, repeat the test on 12 additional dosage units. The requirements of the test are
met if not less than 16 of the 18 dosage units tested have disintegrated.

V. Average Weight:

The following tests provide limits for the permissible variations in the weights of
individual capsules, expressed in terms of the allowable deviation from the average
weight of a sample.

Procedure:-
Weigh 20 intact capsules individually, and determine the average weight. The requirements
are met if each of the individual weights is within the limits of 90% and 110% of the average
weight. The average weight is within +/- 10% of target weight.

If not all of the capsules fall within the aforementioned limits, weigh the 20 capsules
individually. Weigh the emptied shells individually, and calculate for each capsule the net
weight of its contents by subtracting the weight of the shell from the respective gross weight.
Determine the average net content from the sum of the individual net weights. Then
determine the difference between each individual net content and the average net content: the
requirements are met if (a) not more than 2 of the differences are greater than 10% of the
average net content and (b) in no case is the difference greater than 25%.

If more than 2 but not more than 6 capsules deviate from the average between 10% and 25%,
determine the net contents of an additional 40 capsules, and determine the average content of
the entire 60 capsules. Determine the 60 deviations from the new average: the requirements
are met if (a) in not more than 6 of the 60 capsules does the difference exceed 10% of the
average net content and (b) in no case does the difference exceed 25%.

VI. Dimensions of Hard Capsules:

Capsules are solid dosage forms in which the drug is enclosed within either a hard or soft
soluble container or “shell.” The shells are usually formed from gelatin; however, they also
may be made from starch or other suitable substances. Hard-shell capsule sizes range from
No. 5, the smallest, to No. 000, which is the largest, except for veterinary sizes. However,
size No. 00 generally is the largest size acceptable to patients. Size 0 hard gelatin capsules
having an elongated body (known as size OE) also are available, which provide greater fill
capacity without an increase in diameter. Hard gelatin capsules consist of two, telescoping
cap and body pieces.

S. NO. LENGTH OF CAPSULE DIAMETER OF CAPSULE

(mm) (mm)

3
 SPECIFICATIONS OF EMPTY HARD GELATIN CAPSULES OF SIZE 0, SIZE 1 AND SIZE 2

SIZE # 0 SIZE # 1 SIZE # 2

MINIMUM MAXIMUM MINIMUM MAXIMUM MINIMUM MAXIMUM
CAP 7.57mm 7.69mm 6.85mm 6.97mm 6.28mm 6.40mm
DIAMETER 0.298 0.303 0.270 0.274 0.247 0.252
inches inches inches inches inches inches
BODY 7.26mm 7.38mm 6.56mm 6.68mm 6.01mm 6.13mm
DIAMETER 0.286 0.291 0.258 0.263 0.237 0.241
CAP 10.82mm 11.54mm 9.65mm 10.37mm 8.81mm 9.53mm
LENGTH 0.426 0.454 0.380 0.408 0.347 0.375
inches
BODY 18.36mm 19.08mm 16.36mm 17.08mm 14.98mm 15.70mm
LENGTH 0.723 0.751 0.644 0.672 0.590 0.618
CAP DWT. 0.203mm 0.223mm 0.198mm 0.218mm 0.185mm 0.216mm
0.0080 0.0088 0.0078 0.0086 0.0073 0.0085
BODY 0.193mm 0.213mm 0.189mm 0.209mm 0.180mm 0.211mm
DWT. 0.0076 0.0084 0.0075 0.0082 0.0071 0.0083
AVERAGE 97+6 mg 78+5 mg 63+3 mg
WEIGHT

Uses: - 1) Hard gelatin capsules have been used for enclosure of powders or other solid
substances like granules and pellets.

2) Incompatible drugs can be usefully supplied in capsules.

3) To make small tablets from each individual drug and encapsulate them all in
one capsule.
4) Hard gelatin capsules have also been used for drug delivery in bronchial tract.

Result: - Capsules evaluated are within the prescribed limits, & passes all the tests.