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Oral Powders

              Oral powders are generally administered in or with water or another suitable liquid. They may also be swallowed directly.

              Oral powders are presented as single-unit or multiple-unit preparations. For single-unit powders each dose is enclosed in a separate container, for example, a sachet, a paper packet or a vial. Multiple-unit powders require the provision of a measuring device capable of delivering the quantity prescribed.

              Effervescent oral powders are presented as singleunit or multiple-unit powders and generally contain acid substances and either carbonates or bicarbonates 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 For single-unit containers the label states the name(s) and quantity(ies) of active ingredient(s) per container. For multiple-unit containers the label states the name(s) and quantity(ies) of active ingredient(s) in a suitable amount by weight.

Topical Powders

              Topical powders are free from grittiness. They are presented as single-unit or multiple-unit preparations. If a topical powder is specifically intended for use on large open wounds or on severely injured skin, it must be sterile.

              Multiple-unit topical powders should preferably be dispensed in sifter-top containers or in aerosol containers.

              Dusting powders are topical powders consisting of finely divided powders that are intended to be applied to the skin for therapeutic, prophylactic or lubricant purposes. In general, they should be passed through at least a No. 150 sieve to assure freedom from grit that could irritate traumatized areas.

               Labelling The label of topical powders states, where applicable, that the topical powder is sterile.

PREPARATIONS FOR INHALATION

              Preparations for inhalation are solid or liquid preparations that contain one or more active ingredients. They are intended for administration to the lower respiratory tract for local or systemic effect. Preparations for inhalation should not adversely affect the functions of the mucosa of the respiratory tract and its cilia.

              Preparations for inhalation are supplied in multipleunit or single-unit containers provided with a suitable administration device, if necessary.

              Four categories of preparations for inhalation may be distinguished: (1) inhalations; (2) powders for inhalation; (3) inhalation aerosols; (4) inhalants.

              Preparations for inhalation that are converted into an aerosol are generally administered by nebulizers, by pressurized metered-dose inhalers or by dry-powder inhalers.

              Production During the development of a preparation for inhalation which contains an antimicrobial preservative, the effectiveness of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. A suitable method of test together with the criteria for judging the preservative properties of the formulation are described in the “Efficacy of Antimicrobial Preservation” (Appendix 10.6). The size of particles to be inhaled should be adjusted so as to localize their deposition in the lower respiratory tract and verified by suitable methods of particle-size determination.

              For preparations for inhalation that are supplied in single-unit containers provided with a suitable administration device, the single doses released by the administration device are tested for uniformity of volume, weight or content. The content of a unit spray of suspensions for inhalation dispensed in multiple-unit aerosol containers is verified using a suitable number of unit sprays for quantification.

              Minimum fill Preparations for inhalation comply with the test described in the “Minimum Fill” (Appendix 4.26).

              Packaging and storage Preparations for inhalation should be kept in well-closed containers. Aerosol preparations shall be stored at a temperature notexceeding 50º and should be protected from frost.

              Labelling The label of preparations for inhalation states the name(s) and quantity(ies) of any antimicrobial preservative(s).

Inhalations

              Inhalations are solutions or suspensions or emulsions of one or more active ingredients administered by the nasal or oral respiratory route for local or systemic effect.

              As far as possible, liquids not dispensed in aerosol containers are aqueous, isotonic liquids. The pH of the liquid should be not lower than 3 and not higher than 8.5. Co-solvents or suitable solubilizers may be used to increase the solubility of the active ingredients. Aqueous inhalations supplied in multiple-unit containers should contain a suitable antimicrobial preservative at a suitable concentration except where the preparation itself has adequate antimicrobial properties.

              Suspensions are readily dispersible on shaking and the suspension remains sufficiently stable to enable the correct dose to be delivered by the device. Suitable suspension stabilizers may be added.

              Inhalations are usually supplied in glass or plastic containers. If inhalations are provided in concentrated form, they should be diluted in the nebulizers to the prescribed volume with the prescribed liquid before use.

Powders for Inhalation

              Powders for inhalation are powders containing medicinal substances usually diluted with suitable diluents. These powders are normally dispensed in hard gelatin capsules. They may also be administered by mechanical devices that require manually produced pressure or a deep inhalation by the patient, e.g. Cromoglycate Sodium for Inhalation.

              Uniformity of dosage units Powders for inhalation comply with the “Uniformity of Dosage Units” (Appendix 4.28).

              Labelling The label on the container states that the capsules are intended for use in an inhaler and are not to be swallowed.

Inhalation Aerosols

(Note Inhalation aerosols comply with the appropriate requirements for aerosols.)

              Inhalation aerosols are metered-dose preparations. They are drugs or solutions or suspensions or emulsions intended to be inhaled in controlled amounts and are delivered by the actuation of an appropriate metering valve. They contain multiple doses, often exceeding several hundreds. The most common single-dose volumes delivered are from 25 to 100 μl (also expressed as mg) per actuation.

               Production The formulation of inhalation aerosols and the components of the delivery device (i.e., the aerosol container with its integral metering valve and the actuator) should be designed and, where appropriate, the particle size of the active ingredients should be controlled so that, when the inhalation aerosols are used in accordance with the manufacturer’s recommendations, an adequate proportion of the active ingredients is made available for inhalation. A proportion of the active ingredient is deposited on the inner surface of the actuator; the amount available for inhalation is therefore less than the amount released by actuation of the valve.

              Inhalation aerosols should be manufactured in conditions designed to minimize microbial and particulate contaminations.

              Packaging and storage Inhalation aerosols are supplied in suitable containers fitted with an appropriate metering valve that forms an integral part of the container. The containers are usually supplied with an appropriate actuator. Inhalation aerosols should be protected from extremes of temperature and from undue fluctuations in temperature.

              Labelling The label of inhalation aerosols states (1) the quantity(ies) of active ingredient(s) delivered by each actuation of the valve; (2) the instructions for using the inhalation aerosols; (3) any special precautions associated with the use of the inhalation aerosols.

Inhalants

              Inhalants are drugs or combination of drugs which may contain an inert, suspended, diffusing agent. They are intended to release volatile constituents for inhalation either when placed on a pad or when added to hot, but not boiling, water.

              Labelling The label on the container states that the inhalants are not to be taken by mouth.

RECTAL PREPARATIONS

              Rectal preparations are intended for rectal use in order to obtain a systemic or local effect, or they may be intended for diagnostic purposes.

              Several categories of rectal preparations may be distinguished: (1) rectal suppositories; (2) rectal capsules; (3) rectal solutions and suspensions (enemas); (4) powders and tablets for rectal solutions and suspensions; (5) rectal creams; (6) rectal gels; (7) rectal ointments; (8) rectal foams; and (9) rectal tampons.

              Production During the development of a rectal preparation, the formulation for which contains an antimicrobial preservative, the effectiveness of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. A suitable method of testing together with criteria for judging the preservative of the formulation is provided under “Efficacy of Antimicrobial Preservation” (Appendix 10.6).

              In the manufacture, packaging, storage and distribution of rectal preparations, suitable means are taken to ensure their microbial quality; recommendations on this aspect are provided under “Limit for Microbial Contamination” (Appendix 10.5).

              In the manufacture of semi-solid and liquid rectal preparations containing dispersed particles, measures are taken to ensure a suitable and controlled particle size with regard to the intended use.

              Dissolution A suitable test may be required to demonstrate the appropriate release of the active ingredient(s) from solid, single dose preparations, for example the dissolution test for suppositories and soft capsules (Appendix 4.24). Where a dissolution test is prescribed, a disintegration test may not be required.

              Uniformity of dosage units Rectal preparations comply with the “Uniformity of Dosage Units” (Appendix 4.28).

Rectal Suppositories

              Rectal suppositories are solid, single-dose preparations. The shape, volume and consistence of suppositories are suitable for rectal administration.

              They contain one or more active ingredients dispersed or dissolved in a simple or compound excipient which may be soluble or dispersible in water or may melt at body temperature. Excipients such as diluents, adsorbents, surface-active agents, lubricants, antimicrobial preservatives and colouring matter, authorized by the competent authority, may be added if necessary.

              Production Rectal suppositories are prepared by compression or moulding. If necessary, the active ingredient(s) are previously ground and sieved through a suitable sieve. When prepared by moulding, the medicated mass, sufficiently liquified by heating, is poured into suitable moulds. The suppository solidifies on cooling. Various excipients are available for this process, such as hard fat, macrogols, cocoa butter, and various gelatinous mixtures consisting, for example, of gelatin, water and glycerol.

              A suitable test is carried out to demonstrate the appropriate release of the active ingredient(s) from suppositories intended for modified release or for prolonged local action.

              Disintegration Unless intended for modified release or for prolonged local action, rectal suppositories comply with the “Disintegration Test for Suppositories and Pessaries” (Appendix 4.22). For suppositories with a fatty base, examine after 30 minutes and for suppositories with a water-soluble base after 60 minutes, unless otherwise justified and authorized.

              Packaging and storage Rectal suppositories shall be kept in well-closed containers.

              Labelling The label on the container states (1) that they are intended for external use only; (2) the storage conditions.

Rectal Capsules

              Rectal capsules (shell suppositories) are solid, single-dose preparations generally similar to soft capsules as defined in capsules except that they may have lubricating coatings. They are of elongated shape, are smooth and have a uniform external appearance.

              Production A suitable test is carried out to demonstrate the appropriate release of the active ingredient(s) from rectal capsules intended for modified release or prolonged local action.

              Disintegration Unless intended for modified release or for prolonged local action, rectal capsules comply with the “Disintegration Test for Suppositories” (Appendix 4.22). Examine the state of the capsules after 30 minutes, unless otherwise justified and authorized.

Rectal Solutions and Suspensions (Enemas)

              Rectal solutions and suspensions (enemas) are liquid preparations intended for rectal use in order to obtain a systemic or local effect, or they may be intended for diagnostic purposes.

              They are single-dose preparations containing one or more active ingredients dissolved or dispersed in water, glycerol, macrogols or other suitable solvents. Suspensions may show a sediment which is readily dispersible on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be delivered.

              Rectal solutions and suspensions may contain excipients intended, for example, to adjust the viscosity of the preparation, to adjust or stabilize pH, to increase the solubility of the active ingredient(s) or to stabilize the preparation. These substances do not adversely affect the intended medical action or, at the concentrations used, cause undue local irritation.

              Rectal solutions and suspensions are supplied in containers containing a volume in the range of 2.5 ml to 2000 ml. The container is adapted to deliver the preparation to the rectum or it is accompanied by a suitable applicator.

Powders and Tablets for Rectal Solutions and Suspensions

              Powders and tablets intended for the preparation of rectal solutions or suspensions are single-dose preparations which are dissolved or dispersed in water at the time of administration. They may contain excipients to facilitate dissolution or dispersion or to prevent aggregation of the particles.

              After dissolution or suspension, they comply with the requirements for rectal solutions or rectal suspensions, as appropriate.

              Disintegration Tablets for rectal solutions or suspensions disintegrate within 3 minutes when tested as described under “Disintegration Test for Suppositories and Pessaries” (Appendix 4.22), but using water at 15º to 25º.

              Labelling The label on the container states (1) the directions for preparing the rectal solution or suspension; (2) the storage conditions; (3) the period during which the constituted rectal solutions or suspensions may be expected to remain satisfactory for use when prepared and stored in accordance with the manufacturer’s recommendations.

Rectal Creams

              See under Topical Semi-solid Preparations.

Rectal Gels

              See under Topical Semi-solid Preparations.

Rectal Ointments

               See under Topical Semi-solid Preparations.

Rectal Foams

              See under Medicated Foams.

Rectal Tampons

              Rectal tampons are solid, single-dose preparations intended to be inserted into the lower part of the rectum for a limited time.

See also under Medicated Tampons.

SPIRITS

              Spirits are ethanolic or hydroethandic solutions of volatile substances usually prepared by simple solution or by admixture of the ingredients. Some spirits serve as flavouring agents while others have medicinal value. Reduction of the high ethanolic content of spirits by admixture with aqueous preparations often causes turbidity.

              Packaging and storage Spirits shall be kept in tightly closed containers, protected from light to prevent loss by evaporation and to limit oxidative changes.

SYSTEMS

              Systems are preparations that allow for the uniform release or targeting of drugs to the body. These preparations are commonly called drug delivery systems or delivery systems. The most widely used of these are transdermal systems.

Transdermal Systems

              Transdermal drug delivery systems are self-contained, discrete dosage forms that, when applied to intact skin, are designed to deliver the drug(s) through the skin to the systemic circulation. Systems typically comprise an outer covering (barrier), a drug reservoir, which may have a rate controlling membrane, a contact adhesive applied to some or all parts of the system and the system/skin interface, and a protective liner that is removed before applying the system. The activity of these systems is defined in terms of the release rate of the drug(s) from the system. The total duration of drug release from the system and the system surface area may also be stated.

              Labelling The label of transdermal systems states (1) the dose released per unit time; (2) the storage conditions.

Ocular Systems

              Ocular systems are sterile, solid or semi-solid preparations of suitable size and shape, designed to be inserted in the conjunctival cul-de-sac, to produce an ocular effect. They generally consist of a reservoir of active ingredient(s) embedded in a matrix or bounded by a rate-controlling membrane. The active ingredient, which is more or less soluble in physiological fluids, is released over a predetermined period of time. Ocular systems are individually distributed into sterile containers.

              Sterility Unless otherwise specified in the individual monograph, ocular systems comply with the “Sterility Test” (Method I, Appendix 10.1).

              Drug release pattern Ocular systems comply with the test for drug release pattern in the individualmonograph.

              Labelling The label of ocular systems states (1) the dose released per unit time; (2) the storage conditions.

Intrauterine Systems

              An intrauterine system, based on a similar principle but intended for release of drug over a much longer period of time, i.e. one year, is also available.

TABLETS

              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.

              The different categories of tablets that exist include soluble tablets, effervescent tablets, tablets for use in the mouth, and modified-release tablets. 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 and of the components of the dosage form.

              Preparations for alternative applications, such as solution-tablets for injections, irrigations, or for external use, 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.

              Production The following information is intended to provide very broad guidelines concerning the main steps to be followed during production. Tablets may be prepared by three general methods: wet granulation, dry granulation (roll compaction or slugging), and direct compression. The purpose of both wet and dry granulation is to improve flow of the mixture and/or to enhance its compressibility. Tablets are compressed by the application of high pressures, utilizing steel punches and dies, to powders or granulations. However, throughout manufacturing, certain procedures should be validated and monitored by carrying out appropriate inprocess controls.

              For modified-release tablets, a suitable test is carried out to demonstrate the appropriate release of the active ingredient(s).

              Delayed-release tablets are prepared by covering tablets with a gastro-intestinal coating or from granules or particles already covered with a gastro-resistant coating.

              In the manufacture of tablet cores, means are taken to ensure that they possess a suitable mechanical strength to withstand handling without crumbling or breaking. This may be demonstrated by examining the “Friability of Uncoated Tablets” (Appendix 4.30) and the “Resistance to Crushing of Tablets” (Appendix 4.31). Chewable tablets are prepared to ensure that they are easily crushed by chewing.

              Disintegration Comply with the “Disintegration Test for Tablets and Capsules” (Appendix 4.23). For those tablets for which a dissolution requirement is included in the individual monograph, omission of the requirement for disintegration is considered justifiable and is therefore authorized.

              Dissolution Comply with the “Dissolution Test” (Appendix 4.24). Where a dissolution test is specified in the individual monograph, a disintegration test may not be required.

              Uniformity of dosage units Comply with the “Uniformity of Dosage Units” (Appendix 4.28). The test for Content Uniformity is not required for multivitamin and trace element tablets.

              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:

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

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

               (3) the appearance of crystals on the container walls or on the tablets.

              Packaging and storage Tablets should be kept in well-closed containers at a temperature not exceeding 30º and protected from crushing and mechanical shock. Moisture-sensitive forms such as effervescent tablets should be kept in tightly closed containers or moistureproof packs and may require the use of separate packages containing water-adsorbent agents, such as silica gel.

Uncoated Tablets

              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.

              TABLETS FOR SOLUTIONS (SOLUBLE TABLETS) Tablets for solutions are uncoated tablets that dissolve in water to give a clear solution.

              EFFERVESCENT TABLETS 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”.

              DISPERSIBLE TABLETS Dispersible tablets are uncoated tablets that produce a uniform dispersion in water.

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

              TABLETS FOR USE IN THE MOUTH Tablets for use in the mouth are usually uncoated tablets. They are formulated to effect a slow release and local action of the active ingredient (for example, compressed lozenges) or the release and systemic absorption of the active ingredient under the tongue (sublingual tablets) or in the other parts of the mouth. (Certain tablets for use in the mouth may be referred to as “Lozenges”.)

              Chewable tablets Chewable tablets are tablets intended to be chewed, producing a pleasant tasting residue in the oral cavity that is easily swallowed and does not leave a bitter or unpleasant after-taste. These tablets have been used in tablet formulations for children, especially multivitamin formulations, and for the administration of antacids and selected antibiotics. Chewable tablets are prepared by compression, usually utilizing mannitol, sorbitol, or sucrose as binders and fillers, and containing colours and flavours to enhance their appearance and taste.

              Buccal and sublingual tablets Buccal tablets are tablets intended to be inserted in the buccal pouch, and sublingual tablets are intended to be inserted beneath the tongue, where the active ingredient is absorbed directly through the oral mucosa. Few drugs are readily absorbed in this way, but for those that are (such as nitroglycerin and certain steroid hormones), a number of advantages may result.

Coated Tablets

              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, polyhydric alcohols, 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.

              SUGAR-COATED TABLETS Sugar-coated tablets are tablets containing a sugar coating.

              FILM-COATED TABLETS Film-coated tablets are tablets covered with a thin layer of resins, polymers, and/or plasticizers capable of forming a film.

Modified-release Tablets

              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 gastro-intestinal tract.

              DELAYED-RELEASE TABLETS Delayed-release tablets are tablets intended to resist gastric fluid but to release the active ingredient(s) in the 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.

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

               EXTENDED-RELEASE TABLETS Extended-release tablets are tablets designed to slow the rate of release of the active ingredient(s) in the gastro-intestinal tract.

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

TINCTURES

              Tinctures are ethanolic or hydroethanolic solutions usually obtained from dried vegetable or animal matter or from chemical substances. They are usually obtained either using 1 part of drug and 10 parts of extraction solvent or 1 part of drug and 5 parts of extraction solvent. Tinctures are usually clear; a slight sediment may be produced on standing provided that the composition is not changed significantly.

              Production For some preparations, the matter to be extracted must undergo a preliminary treatment, for example, inactivation of enzymes, grinding or defatting. Tinctures are prepared by maceration, percolation or other suitable, justified methods, using Ethanol of suitable concentration. Tinctures may also be obtained by dissolving or diluting extracts in Ethanol of suitable concentration.

              PRODUCTION BY PERCOLATION If necessary, the drug is reduced to pieces of suitable size, mixed thoroughly with a portion of extraction solvent and allowed to stand for an appropriate time. The mixture is transferred to a percolator and the percolate allowed to flow slowly ensuring that the drug is always covered with the remaining extraction solvent. The drug residue may be pressed out and the expressed fluid combined with the percolate.

              PRODUCTION BY MACERATION Unless otherwise prescribed, the drug is reduced to pieces of suitable size, mixed thoroughly with the prescribed extraction solvent and allowed to stand in a closed container for anappropriate time. The drug residue is separated from the extraction solvent and, if necessary, pressed out. In the latter case, the two liquids obtained are combined.

               PRODUCTION FROM EXTRACTS The tincture is prepared by dissolving or diluting an extract, using Ethanol of appropriate concentration. The content of solvent and constituents or, where applicable, the contents of solvent and of dry residue correspond to that of tinc-tures obtained by maceration or percolation.

               When the content of constituents has to be adjusted, such adjustment may be carried out, if necessary, either by adding the extraction solvent of suitable concentration or by adding another tincture of the vegetable or animal matter used for the preparation.

               Ethanol Comply with the limits prescribed in the monograph (Appendix 6.5).

               Methanol and 2-propanol Not more than 0.05 per cent v/v of methanol or 2-propanol (Appendix 5.15), unless otherwise prescribed in the monograph.

               Total solids Comply with the limits prescribed in the monograph (Appendix 7.21).

               Weight per millilitre Comply with the limits prescribed in the monograph (Appendix 4.9).

               Packaging and storage Tinctures should be kept in tightly closed containers, protected from light, in a cool place.

               Labelling The label on the container states (1) the vegetable, animal matter or chemical substances used; (2) where applicable, that fresh vegetable or animal matter was used; (3) the name and concentration of the solvent used for the preparation; (4) the concentration of ethanol in the final tincture; (5) the content of active principle and/or the ratio of starting material to extraction fluid and of starting material to final tincture.

TOPICAL PREPARATIONS

               Topical preparations are drugs intended for topical application in a wide variety of dosage forms.

               Minimum fill Topical preparations except plasters comply with the test described in the “Minimum Fill” (Appendix 4.26).

Applications

               Applications are liquid or semi-liquid preparations containing one or more active ingredients intended for application to the skin. They may contain suitable antimicrobial preservatives, unless the active ingredients or vehicles have sufficient intrinsic antibacterial and antifungal activity. They may contain other suitable auxiliary substances such as stabilizers. They have traditionally been used to administer antiparasitic medications.

Collodions

               Collodions are liquid preparations, usually containing pyroxylin in a mixture of ether and ethanol, that are intended for application to the skin. When they are allowed to dry, a flexible film is formed at the site of application.

               Packaging and storage Collodions should be kept in well-closed containers, at a temperature not exceeding 25º and remote from fire.

Jellies

               See hydrophilic gels under Topical Semi-solid Preparations.

Liniments

               Liniments are liquid or semi-liquid preparations containing one or more active ingredients in suitable vehicles. They are intended to be applied to the unbroken skin with friction. They may contain suitable antimicrobial preservatives.

               Packaging and storage Liniments should be kept in well-closed containers. Certain plastic containers, such as those made from polystyrene, are unsuitable for liniments.

Lotions

               Lotions are liquid or semi-liquid preparations containing one or more active ingredients in suitable vehicles. They are usually intended to be applied to the unbroken skin without friction. Lotions may contain suitable antimicrobial preservatives, unless the active ingredients or vehicles have sufficient intrinsic antibacterial and antifungal activity. They may contain other suitable added substances such as stabilizers. The term “lotion” is applied to solutions or suspensions or emulsions applied topically.

               TOPICAL SOLUTIONS Topical solutions are solutions, usually aqueous but often containing other solvents, such as alcohol and polyols, intended for topical application to the skin, or to the oral mucosal surface.

               TOPICAL SUSPENSIONS Topical suspensions are liquid preparations containing solid particles dispersed in a liquid vehicle, intended for application to the skin.

               TOPICAL EMULSIONS Topical emulsions are liquid preparations in which one liquid is dispersed throughout another liquid in the form of small droplets.

               Packaging and storage Lotions should be kept in well-closed containers.

Mouthwashes

               Mouthwashes are aqueous solutions containing one or more active ingredients. They are intended for use in contact with the mucous membranes of the oral cavity, usually after dilution with warm water. They may contain added substances such as suitable antimicrobial preservatives.

               Packaging and storage Mouthwashes should be kept in well-closed containers.

               Labelling The label of mouthwashes states the directions for the dilution of the mouthwash for use, if appropriate.

Paints

               Paints are solutions or dispersions of one or more active ingredients. They are intended for application to the skin or, in some cases, mucous membranes.

               Packaging and storage Paints should be kept in tightly closed containers.

Plasters

               Plasters are usually solid at ordinary temperature, and are intended for external application. They are used by spreading on cloth, paper, or plastic film and adhering to the skin. Medicated plaster, long used for local or regional drug delivery, are the prototypical transdermal system.

Topical Emulsions

               See under Lotions.

Topical Powders

               See under Powders.

Topical Semi-solid Preparations

               Topical semi-solid preparations are intended to be applied to the skin or to certain mucous surfaces for local action or percutaneous penetration of medicaments, or for their emollient or protective action. They are of homogeneous appearance.

               Topical semi-solid preparations consist of a simple or compound base in which, usually, one or more active substances are dissolved or dispersed. According to its composition, the base may influence the action of the preparation and the release of the active substance(s). The bases may consist of natural or synthetic substances and may be single-phase or multi-phase systems. According to the nature of the base the preparation may have hydrophilic or hydrophobic (lipophilic) properties; it may contain suitable additives such as antimicrobial preservatives, antioxidants, stabilizers, emulsifiers and thickeners.

               If a preparation is specifically intended for use on large open wounds or on severely injured skin, it should be sterile. Preparations required to be sterile must comply with the test for sterility.

               If the particle size of the ingredients is of importance for the therapeutic purpose of a topical semi-solid preparation, the test to be applied should be specified.

               Topical semi-solid preparations can be distinguished into four categories: (1) creams (hydrophobic or hydrophilic); (2) gels (hydrophobic or hydrophilic); (3) ointments (hydrophobic, water-emulsifying or hydrophilic); (4) pastes.

               Sterility Where the preparation is labelled as sterile and unless otherwise directed in the individual monograph, it complies with the “Sterility Test” (Method I, Appendix 10.1).

               Packaging and storage Topical semi-solid preparations should be stored in well-closed containers or, if the preparation contains water or other volatile constituents, in a tightly closed container. The containers are preferably collapsible metal tubes from which the preparation may be readily extruded. Other types of container may be used. Containers for preparations for nasal, aural, vaginal, or rectal use should be adapted to deliver the product to the site of application or should be accompanied by a suitable applicator. They should be stored at a temperature not exceeding 30º unless otherwise prescribed. For creams and gels, they shall not be frozen.

               Labelling The label of topical semi-solid preparations states (1) the name and concentration of any added antimicrobial preservative(s); (2) where applicable, that the preparation is sterile.

               CREAMS Creams are homogeneous, semi-solid preparations consisting of opaque emulsion systems. They are multiphase preparations composed of a lipophilic phase and an aqueous phase.

Hydrophobic creams

               Hydrophobic creams have the lipophilic phase as the continuouss phase. They contain water-in-oil emulsifying agents such as wool fat, sorbitan esters and monoglycerides. Hydrophilic creams Hydrophilic creams have the aqueous phase as the continuous phase. They contain oil-in-water emulsifying agents such as sodium or triethanolamine soaps, sulfated fatty alcohols and polysorbates, combined, if necessary, with water-in-oil emulsifying agents.

               GELS Gels are usually homogeneous, clear, semisolid preparations consisting of a liquid phase within a three-dimensional polymeric matrix with physical or sometimes chemical cross-linkage by means of suitable gelling agents.

               Hydrophobic gels Hydrophobic gel (oleogel) bases usually consist of liquid paraffin with polyethylene or fatty oils gelled with colloidal silica or aluminium or zinc soaps. Hydrophilic gels Hydrophilic gel (hydrogel) bases usually consist of water, glycerol, or propylene glycol gelled with suitable agents such as tragacanth, starch, cellulose derivatives, carboxyvinyl polymers and magnesium aluminium silicates.

               OINTMENTS Ointments are homogeneous, semi-solid preparations intended for external application to the skin or mucous membranes. They are formulated using hydrophobic, hydrophilic, or water-emulsifying bases to provide preparations that are immiscible, miscible, or emulsifiable with skin secretions. They can also be derived from hydrocarbon (fatty), absorption, waterremovable, or water-soluble bases.

               Hydrophobic ointments Hydrophobic (lipophilic) ointments are usually anhydrous and can absorb only small amounts of water. Typical bases used for their formulation are water-insoluble hydrocarbons such as hard, soft, and liquid paraffin, vegetable oil, animal fats, waxes, synthetic glycerides, and polyalkylsiloxanes.

               Water-emulsifying ointments Water-emulsifying ointments can absorb large amounts of water. They typically consist of a hydrophobic fatty base in which a water-in-oil agent, such as wool fat, wool alcohols, sorbitan esters, monoglycerides, or fatty alcohols can be incorporated to render them hydrophilic. They may also be water-in-oil emulsions that allow additional quantities of aqueous solutions to be incorporated. Such ointments are used especially when formulating aqueous liquids or solutions.

               Hydrophilic ointments Hydrophilic ointment bases are either water-removable or water-soluble bases. They are oil-in-water emulsions such as hydrophilic ointment or greaseless ointment bases comprised of water soluble constituents such as mixtures of liquid and solid polyethyleneglycols (macrogols).

               PASTES Pastes are homogeneous, semi-solid preprations usually containing high concentrations of insoluble powdered substances (commonly not less than 20 per cent) dispersed in a suitable base. One class is made from a single phase aqueous gel (e.g., zinc oxide gelatin paste). The other class, the fatty pastes (e.g., zinc oxide paste) consists of thick, stiff ointments that do not ordinarily flow at body temperature. The pastes should adhere well to the skin. In many cases they form a protective film that controls the evaporation of water.

Topical Solutions

               See under Lotions. 

Topical Suspensions

               See under Lotions.

VAGINAL PREPARATIONS

               Vaginal preparations are liquid, semi-solid preparations intended for administration to the vagina usually in order to obtain a local effect. They contain one or more active ingredients in a suitable basis. Several categories of vaginal preparations may be distinguished: (1) moulded pessaries; (2) vaginal tablets; (3) vaginal capsules; (4) vaginal foams; and (5) vaginal tampons.

               Production In the manufacturing, packaging, storage and distribution of vaginal preparations, suitable means are taken to ensure their microbial quality; recommendations on this aspect are provided under “Limits for Microbial Contamination” (Appendix 10.5).

               Disintegration Vaginal preparations comply with the “Disintegration Test for Suppositories” (Appendix 4.22).

Uniformity of dosage units Vaginal preparations comply with the “Uniformity of Dosage Units” (Appendix 4.28).

Moulded Pessaries

               Moulded pessaries are solid, single-dose preparations. They have various shapes, usually ovoid, with a volume and consistence suitable for insertion into the vagina. Apart from their shape they conform to rectal suppositories.

               Moulded pessaries are prepared using the method and excipients described for rectal suppositories. The active ingredient(s) are dispersed or dissolved in a simple or compound basis, which may be soluble, insoluble but melting at body temperature or dispersible in water.

               Vaginal preparations which conform to the definition of moulded pessaries may be prepared by compression. They comply with the requirements for moulded pessaries.

               Production A suitable test is carried out to demonstrate the appropriate release of the active ingredient(s) from pessaries intended for modified release or prolonged local action.

               Packaging and storage Moulded pessaries shall be kept in well-closed containers.

               Labelling The label on the container states (1) that they are intended for external use only; (2) the storage conditions.

Vaginal Tablets

               Vaginal tablets (compressed pessaries) are solid single-dose preparations. They generally conform to the definitions of uncoated or film-coated tablets in Tablets.

               Production A suitable test is carried out to demonstrate the appropriate release of the active ingredient(s) from vaginal tablets intended for modified release or prolonged local action.

Vaginal Capsules

               Vaginal capsules (shell pessaries) are solid, single dose preparations. They are generally similar to soft capsules, differing only in their shape and size. Vaginal capsules have various shapes, usually ovoid. They are smooth and have a uniform external appearance.

               Production A suitable test is carried out to demonstrate the appropriate release of the active ingredients(s) from vaginal capsules intended for modified release or prolonged local action.

Vaginal Foams

               See under Medicated Foams.

Vaginal Tampons

               Vaginal tampons are solid, single-dose preparations intended to be inserted in the vagina for a limited time. See also under Medicated Tampons.