CAPSULES

(Ph. Eur. monograph 0016)

Capsules comply with the requirements of the European Pharmacopoeia. These requirements are reproduced below.

Ph Eur

The requirements of this monograph do not necessarily apply to preparations that are presented as capsules intended for use other than by oral administration. Requirements for such preparations may be found, where appropriate, in other general monographs, for example Rectal preparations (1145) and Vaginal preparations (1164)

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 capsule shells are made of gelatin or other substances, the consistency of which may be adjusted by the addition of substances such as glycerol or sorbitol. Excipients such as surface-active agents, opaque fillers, antimicrobial preservatives, sweeteners, colouring matter authorised by the competent authority and flavouring substances may be added. The capsules may bear surface markings.

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.

Where applicable, containers for capsules comply with the requirements of Materials used for the manufacture of containers (3.1 and subsections) and Containers (3.2 and subsections).

Several categories of capsules may be distinguished:

• — hard capsules;

• — soft capsules;

• — gastro-resistant capsules;

• — modified-release capsules;

• — cachets.

In the manufacture, packaging, storage and distribution of capsules, suitable measures are taken to ensure their microbial quality; recommendations on this aspect are provided in the text on Microbiological quality of pharmaceutical preparations (5.1.4).

Capsules comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.

Unless otherwise prescribed or justified and authorised, capsules with a content of active substance less than 2 mg or less than 2 per cent of the fill mass comply with test B for uniformity of content of single-dose preparations. If the preparation has more than one active substance, the requirement applies only to those ingredients which correspond to the above conditions.

Capsules comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active substances, the test for uniformity of mass is not required.

A suitable test may be carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in Dissolution test for solid dosage forms (2.9.3).

Where a dissolution test is prescribed, a disintegration test may not be required.

Store at a temperature not exceeding 30 °C.

The label states the name of any added antimicrobial preservative.

Hard capsules have shells consisting of 2 prefabricated, cylindrical sections, each of which has one rounded, closed end and one open end.

The active substance(s), usually in solid form (powder or granules), are filled into one of the sections that is then closed by slipping the other section over it. The security of the closure may be strengthened by suitable means.

Hard capsules comply with the test for disintegration of tablets and capsules (2.9.1). Use water R as the liquid medium. When justified and authorised, 0.1 M hydrochloric acid or artificial gastric juice R may be used as the liquid medium. If the capsules float on the surface of the water, a disc may be added. Operate the apparatus for 30 min, unless otherwise justified and authorised.

Soft capsules have thicker shells than those of hard capsules. The shells consist of a single part and are of various shapes.

Soft capsules are usually formed, filled and sealed in one operation, but for extemporaneous use the shell may be prefabricated. The shell material may contain an active substance.

Liquids may be enclosed directly; solids are usually dissolved or dispersed in a suitable vehicle to give a solution or dispersion of a paste-like consistency.

There may be partial migration of the constituents from the capsule contents into the shell and vice versa because of the nature of the materials and the surfaces in contact.

Soft capsules comply with the test for disintegration of tablets and capsules (2.9.1). Use water R as the liquid medium. When justified and authorised, 0.1 M hydrochloric acid or artificial gastric juice R may be used as the liquid medium. Add a disc to each tube. Liquid active substances dispensed in soft capsules may attack the disc; in such circumstances and where authorised, the disc may be omitted. Operate the apparatus for 30 min, unless otherwise justified and authorised. If the capsules fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 capsules omitting the discs.

Modified-release capsules are hard or soft capsules in which the contents or the shell or both contain special excipients or are prepared by a special process designed to modify the rate, the place or the time at which the active substance(s) are released.

Modified-release capsules include prolonged-release capsules and delayed-release capsules.

A suitable test is carried out to demonstrate the appropriate release of the active substance(s).

Gastro-resistant capsules are delayed-release capsules that are intended to resist the gastric fluid and to release their active substance or substances in the intestinal fluid. Usually they are prepared by filling capsules with granules or with particles covered with a gastro-resistant coating, or in certain cases, by providing hard or soft capsules with a gastro-resistant shell (enteric capsules).

For capsules filled with granules or filled with particles covered with a gastro-resistant coating, a suitable test is carried out to demonstrate the appropriate release of the active substance(s).

For capsules with a gastro-resistant shell carry out the test for disintegration (2.9.1) with the following modifications. Use 0.1 M hydrochloric acid as the liquid medium and operate the apparatus for 2 h, or other such time as may be authorised, without the discs. Examine the state of the capsules. The time of resistance to the acid medium varies according to the formulation of the capsules to be examined. It is typically 2 h to 3 h but even with authorised deviations it must not be less than 1 h. No capsule shows signs of disintegration or rupture permitting the escape of the contents. Replace the acid by phosphate buffer solution pH 6.8 R. When justified and authorised, a buffer solution of pH 6.8 with added pancreas powder (for example, 0.35 g of pancreas powder R per 100 mL of buffer solution) may be used. Add a disc to each tube. Operate the apparatus for 60 min. If the capsules fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 capsules omitting the discs.

For capsules prepared from granules or particles already covered with a gastro-resistant coating, a suitable test is carried out to demonstrate the appropriate release of the active substance(s), for example the test described in Dissolution test for solid dosage forms (2.9.3).

Cachets are solid preparations consisting of a hard shell containing a single dose of one or more active substances. The cachet shell is made of unleavened bread usually from rice flour and consists of 2 prefabricated flat cylindrical sections. Before administration, the cachets are immersed in water for a few seconds, placed on the tongue and swallowed with a draught of water.

The label states the method of administration of the cachets.

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