TABLETS

(Ph Eur monograph 0478)

Tablets 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 tablets 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), Vaginal preparations (1164) and Oromucosal preparations (1807). This monograph does not apply to lozenges, oral pastes and oral gums. Where justified and authorised, the requirements of this monograph do not apply to tablets for veterinary use.

Tablets are solid preparations each containing a single dose of one or more active substances. They are obtained by compressing uniform volumes of particles or by another suitable manufacturing technique, such as extrusion, moulding or freeze-drying (lyophilisation). Tablets are intended for oral administration. Some are swallowed whole, some after being chewed, some are dissolved or dispersed in water before being administered and some are retained in the mouth where the active substance is liberated.

The particles consist of one or more active substances with or without excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the preparation in the digestive tract, colouring matter authorised by the competent authority and flavouring substances.

Tablets are usually straight, circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be bevelled. They may have break-marks and may bear a symbol or other markings. Tablets may be coated.

Where applicable, containers for tablets comply with the requirements for materials used for the manufacture of containers (3.1 and subsections) and containers (3.2 and subsections).

Several categories of tablets for oral use may be distinguished:

• — uncoated tablets;

• — coated tablets;

• — effervescent tablets;

• — soluble tablets;

• — dispersible tablets;

• — orodispersible tablets;

• — gastro-resistant tablets;

• — modified-release tablets;

• — tablets for use in the mouth;

• — oral lyophilisates.

Tablets are usually prepared by compressing uniform volumes of particles or particle aggregates produced by granulation methods. In the manufacture of tablets, means are taken to ensure that they possess a suitable mechanical strength to avoid crumbling or breaking on handling or subsequent processing. This may be demonstrated using the tests described in chapters 2.9.7. Friability of uncoated tablets and 2.9.8. Resistance to crushing of tablets. Chewable tablets are prepared to ensure that they are easily crushed by chewing.

Subdivision of tablets  Tablets may bear a break-mark or break-marks and may be subdivided in parts, either to ease the intake of the medicinal product or to comply with the posology. In the latter case, subdivision must be assessed and authorised by the competent authority. In order to ensure that the patient will receive the intended dose, the efficacy of the break-mark(s) must be assessed during the development of the product, in respect of uniformity of mass of the subdivided parts. Each authorised dose must be tested using the following test.

Take 30 tablets at random, break them by hand and, from all the parts obtained from 1 tablet, take 1 part for the test and reject the other part(s). Weigh each of the 30 parts individually and calculate the average mass. The tablets comply with the test if not more than 1 individual mass is outside the limits of 85 per cent to 115 per cent of the average mass. The tablets fail to comply with the test if more than 1 individual mass is outside these limits, or if 1 individual mass is outside the limits of 75 per cent to 125 per cent of the average mass.

In the manufacture, packaging, storage and distribution of tablets, suitable means are taken to ensure their microbiological quality; recommendations on this aspect are provided in chapter 5.1.4. Microbiological quality of pharmaceutical preparations.

Tablets comply with the test 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, tablets with a content of active substance less than 2 mg or less than 2 per cent of the total mass comply with test A. If the preparation has more than 1 active substance, the requirement applies only to those substances that correspond to the above conditions.

Unless otherwise justified and authorised, coated tablets other than film-coated tablets comply with test A irrespective of their content of active substance(s).

Uncoated tablets and, unless otherwise justified and authorised, film-coated tablets comply with the test. If the test for uniformity of content is prescribed or justified and authorised 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 chapter 2.9.3. Dissolution test for solid dosage forms.

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

Uncoated tablets include single-layer tablets resulting from a single compression of particles and multi-layer tablets consisting of concentric or parallel layers obtained by successive compression of particles of different composition. The excipients used are not specifically intended to modify the release of the active substance in the digestive fluids.

Uncoated tablets conform to the general definition of tablets. A broken section, when examined under a lens, shows either a relatively uniform texture (single-layer tablets) or a stratified texture (multi-layer tablets) but no signs of coating.

Uncoated tablets comply with the test. Use water R as the liquid. Add a disc to each tube. Operate the apparatus for 15 min, unless otherwise justified and authorised, and examine the state of the tablets. If the tablets fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets omitting the discs.

Chewable tablets are not required to comply with the test.

Coated tablets are tablets covered with one or more layers of mixtures of various substances such as natural or synthetic resins, gums, gelatin, inactive and insoluble fillers, sugars, plasticisers, polyols, waxes, colouring matter authorised by the competent authority and sometimes flavouring substances and active substances. The substances used as coatings are usually applied as a solution or suspension in conditions in which evaporation of the vehicle occurs. When the coating is a very thin polymeric coating, the tablets are known as film-coated tablets.

Coated tablets have a smooth surface, which is often coloured and may be polished; a broken section, when examined under a lens, shows a core surrounded by one or more continuous layers with a different texture.

Where justified, uniformity of mass or uniformity of content of coated tablets other than film-coated tablets may be ensured by control of the cores.

Coated tablets other than film-coated tablets comply with the test. Use water R as the liquid. Add a disc to each tube. Operate the apparatus for 60 min, unless otherwise justified and authorised, and examine the state of the tablets. If any of the tablets has not disintegrated, repeat the test on a further 6 tablets, replacing water R with 0.1 M hydrochloric acid.

Film-coated tablets comply with the disintegration test prescribed above except that the apparatus is operated for 30 min, unless otherwise justified and authorised.

If coated tablets or film-coated tablets fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets omitting the discs.

Chewable coated tablets are not required to comply with the test.

Effervescent tablets are uncoated tablets generally containing acid substances and carbonates or hydrogen carbonates, which react rapidly in the presence of water to release carbon dioxide. They are intended to be dissolved or dispersed in water before administration.

Place 1 tablet in a beaker containing 200 ml of water R at 15-25 °C; numerous bubbles of gas are evolved. When the evolution of gas around the tablet or its fragments ceases the tablet has disintegrated, being either dissolved or dispersed in the water so that no agglomerates of particles remain. Repeat the operation on 5 other tablets. The tablets comply with the test if each of the 6 tablets used disintegrates in the manner prescribed within 5 min, unless otherwise justified and authorised.

Soluble tablets are uncoated or film-coated tablets. They are intended to be dissolved in water before administration. The solution produced may be slightly opalescent due to the added excipients used in the manufacture of the tablets.

Soluble tablets disintegrate within 3 min, using water R at 15-25 °C.

Dispersible tablets are uncoated or film-coated tablets intended to be dispersed in water before administration, giving a homogeneous dispersion.

Dispersible tablets disintegrate within 3 min, using water R at 15-25 °C.

Place 2 tablets in 100 ml of water R and stir until completely dispersed. A smooth dispersion is produced, which passes through a sieve screen with a nominal mesh aperture of 710 µm.

Orodispersible tablets are uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed.

Orodispersible tablets disintegrate within 3 min.

Modified-release tablets are coated or uncoated tablets that contain special excipients or are prepared by special procedures, or both, designed to modify the rate, the place or the time at which the active substance(s) are released.

Modified-release tablets include prolonged-release tablets, delayed-release tablets and pulsatile-release tablets.

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

Gastro-resistant tablets are delayed-release tablets that are intended to resist the gastric fluid and to release their active substance(s) in the intestinal fluid. Usually they are prepared from granules or particles already covered with a gastro-resistant coating or in certain cases by covering tablets with a gastro-resistant coating (enteric-coated tablets).

Tablets covered with a gastro-resistant coating conform to the definition of coated tablets.

For tablets 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 tablets covered with a gastro-resistant coating, carry out the test with the following modifications. Use 0.1 M hydrochloric acid as the liquid. Operate the apparatus for 2 h, or another such time as may be justified and authorised, without the discs and examine the state of the tablets. The time of resistance to the acid medium varies according to the formulation of the tablets to be examined. It is typically 2 h to 3 h but even with authorised deviations is not less than 1 h. No tablet shows signs of either disintegration (apart from fragments of coating) or cracks that would allow the escape of the contents. Replace the acid by phosphate buffer solution pH 6.8 R and add a disc to each tube. Operate the apparatus for 60 min and examine the state of the tablets. If the tablets fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets omitting the discs.

For tablets 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 chapter 2.9.3. Dissolution test for solid dosage forms.

Tablets for use in the mouth are usually uncoated tablets. They are formulated to effect a slow release and local action of the active substance(s) or the release and absorption of the active substance(s) at a defined part of the mouth. They comply with the requirements of the monograph Oromucosal preparations (1807).

Oral lyophilisates are solid preparations intended either to be placed in the mouth or to be dispersed (or dissolved) in water before administration.

Oral lyophilisates are obtained by freeze-drying (lyophilisation), involving division into single doses, freezing, sublimation and drying of usually aqueous, liquid or semi-solid preparations.

Place 1 oral lyophilisate in a beaker containing 200 ml of water R at 15-25 °C. It disintegrates within 3 min. Repeat the test on 5 other oral lyophilisates. They comply with the test if all 6 have disintegrated.

Oral lyophilisates comply with the test; the limits are approved by the competent authority.

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