Compendial standards and regulatory requirements for

capsules
i. Added substances
Non-medicinal substances added to official preparations, including capsules, to
serve different pharmaceutical purposes thus ensuring product acceptability in
terms of manufacturability, appearance and performance may be used only if they:

1. Are harmless in the quantities used.

2. Do not exceed the minimum amounts required to provide their intended effect.
3. Do not impair the product’s bioavailability, therapeutic efficacy, or safety.
4. Do not interfere with requisite compendial assays and tests.

ii. Disintegration time test for capsules

The compendial disintegration test for hard and soft gelatin capsules follows the
same procedure and uses the same apparatus described in the article “Quality
Control Tests for Tablets”. 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˚C and observed over the time described in the individual
monograph.
To fully satisfy the test, the capsules disintegrate completely into a soft mass with
no firm core and only some fragments of the capsule shell.

iii. Dissolution test for capsules

The compendial dissolution test for capsules uses the same apparatus, dissolution
medium, and test as that for uncoated and plain coated tablets. However, in
instances in which the capsule shells interfere with the analysis, the contents of a
specified number of capsules can be removed and the empty capsule shells
dissolved in the dissolution medium before proceeding with the sampling and
chemical analysis.

If the capsule floats on the surface of the dissolution fluid, a small, loose piece of
nonreactive material, such as a few turns of a wire helix, may be attached to the
dosage form to force it to sink to the bottom of the vessel.
iv. Uniformity of weight
The uniformity of dosage units may be demonstrated by determining weight
variation and/or content uniformity. The test for uniformity of weight is performed
as follows.

a. Hard shell capsules

Ten randomly selected capsules are individually weighed (to obtain their gross
weights) and their contents removed. The emptied shells are individually weighed
and the net weight of the contents calculated by subtracting the weight of the shell
from the respective gross weight.

From the results of an assay performed as directed in the individual monograph,

the content of active ingredient in each of the capsules is determined.

b. Soft shell capsules

The gross weight of ten randomly selected intact capsules is determined
individually. Then each capsule is cut open with a suitable clean, dry cutting
instrument e.g., scissors or a sharp blade, and the contents are removed by washing
with a suitable solvent. The solvent is allowed to evaporate at room temperature
over a period of about 30 minutes, with precautions taken to avoid uptake or loss
of moisture. The individual shells are weighed and the net contents calculated.
From the results of the assay directed in the individual monograph, the content of
active ingredient in each of the capsules is determined.

v. Content uniformity
Unless otherwise stated in the United States Pharmacopeia (USP) monograph for
an individual capsule, the amount of drug substance, determined by assay, is within
the range of 85.0 % to 115.0 % of the label claim for nine (9) of ten (10) dosage
units assayed, with no unit outside the range of 75.0 % to 125.0 % of the labelled
drug content. Additional tests are prescribed when two or three dosage units are
outside of the desired range but within the stated extremes.

vi. Stability testing

Stability testing of capsules is performed to determine the intrinsic stability of the
active drug molecule and the influence of environmental factors (e.g., temperature,
light, humidity), formulation components, and the container and closure system.
The battery of stress-testing, long-term stability and accelerated stability tests help
determine the appropriate storage conditions and the product’s anticipated shelf
life.
 vii. Content labelling requirement
All official capsules must be labelled to express the quantity of each active
ingredient in each dosage unit.

viii. Containers for dispensing capsules

There are specifications listed in the USP prescribing the type of container suitable
for the repackaging or dispensing of each official capsule and tablet. Depending on
the item, the container might be required to be tight, well-closed, and light-resistant
and/or a combination of these.
ix. Moisture permeation test
The USP requires determination of the moisture-permeation characteristics of
single-unit and unit dose containers to assure their suitability for packaging
capsules. The degree and rate of moisture penetration is determined by packaging
the dosage unit together with a colour-revealing desiccant pellet, exposing the
packaged unit to known relative humidity over a specified time, observing the
desiccant pellet for colour change (indicating absorption of moisture) and
comparing the pretest and posttest weight of the packaged unit.

Advantages of capsules
 Capsules are convenient means of eliminating unpleasant taste and odour of drugs
by enclosing ingredients in an almost tasteless and odourless shell.
 Capsules are elegant in appearance
 They are relatively easy to swallow (suitable shape and slippery when moistened)
 Consumer preference regarding ease of swallowing, convenience, and taste can
improve compliance.
 They are easily filled either extemporaneously or in large quantities commercially.
 Capsules (generally soft shell capsules) may be formulated to increase the
bioavailability of poorly soluble drugs.
 Capsules offer opportunities for product differentiation via colour, shape, and size
and product line extension.
 Capsules are made from gelatin; hence they are therapeutically inert.
 The stability of therapeutic agents may be improved in a capsule formulation.
 Disadvantages of capsules
 Capsules are unsuitable for very small children
 They cannot be used for substances that react with or dissolve gelatin, the major
component
 Capsules become brittle under very dry conditions and may crack during the filling
process.
 They absorb moisture and soften under high humidity.
 Potential stability problems may be associated with capsules containing liquid fills.
 The manufacture of capsules (generally softgels) require specialist manufacture
and incur high production costs.

References
 Allen L. and Ansel H. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug
Delivery Systems. Philadelphia: Lipincott Williams and Wilkins.
 Aulton, M. and Taylor, K. (2013). Aulton’s Pharmaceutics: The Design and
Manufacture of Medicines, (4th ed.). Edinburgh: Churchill Livingstone.
 Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics – Basic Principles and
Application to Pharmacy Practice. USA: Academic Press.
 Felton, L. (2012). Remington Essentials of Pharmaceutics. UK: Pharmaceutical
press.
 Ghosh, T. and Jasti, B. (2005). Theory and Practice of Contemporary
Pharmaceutics. USA: CRC Press LLC.
 Hoag, S. (2017). Capsules Dosage Form: Formulation and Manufacturing
Considerations. In Y. Qui, Y. Chen, G. Zhang, L. Yu, and R. Mantri
(Eds.), Developing Solid Oral Dosage Forms – Pharmaceutical Theory and
Practice, (2nd ed.) (pp. 723-747). UK: Elsevier Inc.
 Jones D. (2008). Fasttrack Pharmaceutics – Dosage Form and Design. London:
Pharmaceutical Press.
 Lachman, L., Lieberman, H. and Kangi, J. (1990). The Theory and Practice of
Industrial Pharmacy (3rd ed.). USA: Lea & Febiger.
 Ofoefule, S. (2002). Textbook of Pharmaceutical Technology and Industrial
Pharmacy. Nigeria: Samakin (Nig) Enterprise.
 Shayne, C. (2008). Pharmaceutical Manufacturing Handbook: Production and
Processes. New Jersey: John Wiley & Sons, Inc.