Monographs: Dosage forms: General monographs: Tablets

Monographs: Dosage forms: General monographs: Tablets

Definition : Tablets are solid dosage forms containing one or more active ingredients. They are obtained by single or multiple compression (in certain cases they are moulded) and may be uncoated or coated. They are usually intended for oral administration, but preparations for alternative applications, such as implants, solution-tablets for injections, irrigations, or for external use, vaginal tablets, etc., are also available in this presentation. These preparations may require a special formulation, method of manufacture, or form of presentation, appropriate to their particular use. For this reason they may not comply with certain sections of this monograph.

The different categories of tablet that exist include soluble tablets, effervescent tablets, tablets for use in the mouth, and modified-release tablets. Unless otherwise specified in the individual monograph, tablets are normally circular in shape, and their surfaces are flat or convex. Tablets may have lines or break-marks, symbols, or other markings. They should be sufficiently hard to withstand handling, including packaging, storage, and transportation, without crumbling or breaking.


Tablets may contain excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the dosage forms and the active ingredient(s) in the gastrointestinal tract, colouring matter, and flavouring substances.When such excipients are used, it is necessary to ensure that they do not adversely affect the stability, dissolution rate, bioavailability, safety, or efficacy of the active ingredient(s); there must be no incompatibility between any of the components of the dosage form.

Manufacture

The manufacturing processes should meet the requirements of Good Manufacturing Practice, especially with regard to cross-contamination. The following information is intended to provide very broad guidelines concerning the main steps to be followed during production, indicating those that are the most important.

The particle size of the active ingredient(s) is of primary significance in determining the rate and extent of dissolution, the bioavailability, and the uniformity of a drug product, especially for substances of low solubility in aqueous media. In order to obtain a suitable formulation, it is usually necessary to mix the active ingredient(s) with a number of excipients. It is essential that such mixing is carried out in a manner that ensures homogeneity. Sometimes, the physical characteristics of the mixture allow it to be directly compressed, but it is usually necessary to granulate before compression, either by wet granulation or precompression (slugging).

The granulate and powders normally need to be mixed with lubricants and/or disintegrating agents. The use of excessive amounts of lubricants should be avoided since these will deleteriously affect the tablets. The final tablet mixture is volumetrically fed into the die cavity to ensure that the tablets are of a uniform mass when compressed. The tablets may be coated, either in coating pans or by an air-suspension technique. A hydrophobic subcoat applied to the core of sugar-coated tablets may reduce dissolution.

Throughout manufacturing, certain procedures should be validated and monitored by carrying out appropriate in-process controls. These should be designed to guarantee the effectiveness of each stage of production. In-process controls during tablet production should include the particle size of the active ingredient(s), the homogeneity and moisture content of the mixture and/or granulate, the size of granules, the flow of the final mixture, and the dimensions (thickness, diameter), uniformity of mass, hardness and/or crushing force, friability, disintegration, or dissolution rate (e.g. for modified-release tablets) of the finished dosage form. Attention should be paid to the uniformity of mass of tablet cores before coating.

Packaging must be adequate to protect the tablets from light, moisture, and damage during packaging and transportation.

Visual inspection

Unpack and inspect at least 20 tablets. They should be undamaged, smooth, and usually of uniform colour.

Evidence of physical instability is demonstrated by:

    - presence of excessive powder and/or pieces of tablets at the bottom of the container (from abraded, crushed, or broken tablets);

    - cracks or capping, chipping in the tablet surfaces or coating, swelling, mottling, discoloration, fusion between tablets;

    - the appearance of crystals on the container walls or on the tablets.

Uniformity of mass

Tablets comply with the test for 5.2 Uniformity of mass for single-dose preparations, unless otherwise specified below or in the individual monograph.

Uniformity of content

A requirement for compliance with the test for 5.1 Uniformity of content for single-dose preparations is specified in certain individual monographs for sugar-coated or enteric-coated tablets, where the test for 5.2 Uniformity of mass for single-dose preparations does not apply. In addition, a requirement is specified in certain individual monographs where the active ingredient is 5% or less of the total formulation. In such cases the test for 5.2 Uniformity of mass for single-dose preparations is not required.

Dissolution test

Where a requirement for the "Dissolution test" is specified in the individual monograph, the 5.3 Disintegration test for tablets and capsules is not required.

Labelling

Every pharmaceutical preparation must comply with the labelling requirements established under Good Manufacturing Practice.

The label should include:

    (1) the name of the pharmaceutical product;

    (2) the name(s) of the active ingredient(s); International Nonproprietary Names (INN) should be used wherever possible;

    (3) the amount of the active ingredient(s) in each tablet and the number of tablets in the container;

    (4) the batch (lot) number assigned by the manufacturer;

    (5) the expiry date and, when required, the date of manufacture;

    (6) any special storage conditions or handling precautions that may be necessary;

    (7) directions for use, warnings, and precautions that may be necessary; and

    (8) the name and address of the manufacturer or the person responsible for placing the product on the market.

Storage

Tablets should be kept in well-closed containers and protected from light, moisture, crushing, and mechanical shock. Any special storage conditions should be stated on the label. Tablets should be able to withstand handling, including packaging and transportation, without losing their integrity. Moisture-sensitive forms, such as effervescent tablets, should be stored in tightly closed containers or moisture-proof packs and may require the use of separate packages containing water-adsorbent agents, such as silica gel.

Additional special packaging, storage, and transportation recommendations are specified in the individual monograph.

Requirements for specific types of tablets

Uncoated tablets

Definition

The majority of uncoated tablets are made in such a way that the release of active ingredients is unmodified. 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.

Disintegration test

Uncoated tablets, except effervescent tablets, tablets for use in the mouth, and chewable tablets, comply with 5.3 Disintegration test for tablets and capsules. Operate the apparatus for 15 minutes, unless otherwise specified in the individual monograph, and examine the state of the tablets.

Soluble tablets (tablets for solutions)

Definition

Soluble tablets are uncoated tablets that dissolve in water to give a clear solution.

Disintegration test

Soluble tablets comply with 5.3 Disintegration test for tablets and capsules. Use water at room temperature, and operate the apparatus for 5 minutes, unless otherwise specified in the individual monograph.

Effervescent tablets

Definition

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

Labelling

The label should state: "Not to be swallowed directly".

Disintegration test

Effervescent tablets comply with 5.3 Disintegration test for tablets and capsules. Place one tablet in a 250-ml beaker containing 200 ml of water at room temperature. Numerous bubbles of gas are evolved. When the evolution of gas around the tablet or its fragments ceases, the tablet should have disintegrated, being either dissolved or dispersed in the water so that no agglomerates remain. Repeat the operation on five additional tablets. The tablets comply with the test if each of the six tablets used in the test disintegrates within 5 minutes, unless otherwise specified in the individual monograph.

Tablets for use in the mouth (sublingual, buccal) and chewable tablets

Definition

Tablets for use in the mouth and chewable tablets are usually uncoated. They are formulated to effect a slow release and local action of the active ingredient(s) (for example, compressed lozenges) or the release and absorption of the active ingredient(s) under the tongue (sublingual tablets) or in other parts of the mouth (buccal) for systemic action.

Coated tablets

Definition

Coated tablets are tablets covered with one or more layers of mixtures of substances such as natural or synthetic resins, polymers, gums, fillers, sugars, plasticizers, polyols, waxes, colouring matters, flavouring substances, and sometimes also active ingredients. A broken section, when examined under a lens, shows a core which is surrounded by a continuous layer of a different texture.

The tablets may be coated for a variety of reasons such as protection of the active ingredients from air, moisture, or light, masking of unpleasant tastes and odours, or improvement of appearance. The substance used for coating is usually applied as a solution or suspension.

Three main categories of coated tablet may be distinguished: sugar-coated, film-coated, and certain modified-release tablets.

Sugar-coated tablets

Uniformity of mass

The test for 5.2 Uniformity of mass for single-dose preparations, does not apply to sugar-coated tablets (see in-process controls under "Manufacture").

Disintegration test

Sugar-coated tablets comply with 5.3 Disintegration test for tablets and capsules. Operate the apparatus for 60 minutes, unless otherwise specified in the individual monograph, using water, and examine the state of the tablets. If any of the tablets has not disintegrated, repeat the test on an additional six tablets, using hydrochloric acid (0.1 mol/l) VS.

All six tablets must disintegrate.

Film-coated tablets

Definition

A film-coated tablet is covered with a thin layer of resins, polymers, and/or plasticizers capable of forming a film.

Disintegration test

Film-coated tablets comply with 5.3 Disintegration test for tablets and capsules. Operate the apparatus for 30 minutes, and examine the state of the tablets.

Modified-release tablets

Definition

Modified-release tablets are coated, uncoated, or matrix tablets containing excipients or prepared by procedures which, separately or together, are designed to modify the rate of release of the active ingredient(s) in the gastrointestinal tract.

    Extended-release tablets

    Definition

    Extended-release tablets are designed to slow the rate of release of the active ingredient(s) in the gastrointestinal tract.

    All requirements for these specialized dosage forms are given in the individual monographs.

    Delayed-release tablets (enteric-coated tablets)

    Definition

    Delayed-release tablets are intended to resist gastric fluid but disintegrate in intestinal fluid. This is achieved by using coating substances such as cellacefate (cellulose acetate phthalate) and anionic copolymers of methacrylic acid and its esters. It is sometimes necessary to apply more than one layer.

Uniformity of mass

The test for 5.2 Uniformity of mass for single-dose preparations does not apply to delayed-release tablets.

Disintegration test

Delayed-release tablets comply with 5.3 Disintegration test for tablets and capsules, using hydrochloric acid (0.1 mol/l) VS as the immersion fluid. Operate the apparatus for 2 hours, unless otherwise specified in the individual monograph (but in any case for not less than 1 hour), and examine the state of the tablets. No tablet should show signs of either disintegration (apart from fragments of coating) or cracks that would allow the contents to escape. Replace the acid by phosphate buffer solution, pH 6.8, TS. Operate the apparatus for 60 minutes and examine the state of the tablets.