Oromucosal Preparations
Oromucosal Preparations comply with the requirements of the European Pharmacopoeia. These requirements are reproduced below.
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DEFINITION
Oromucosal preparations are solid, semi-solid or liquid preparations, containing one or more active substances intended for administration to the oral cavity and/or the throat to obtain a local or systemic effect. Preparations intended for a local effect may be designed for application to a specific site within the oral cavity such as the gums (gingival preparations) or the throat (oropharyngeal preparations). Preparations intended for a systemic effect are designed to be absorbed primarily at one or more sites on the oral mucosa (e.g. sublingual preparations). Mucoadhesive preparations are intended to be retained in the oral cavity by adhesion to the mucosal epithelium and may modify systemic drug absorption at the site of application. For many oromucosal preparations, it is likely that some proportion of the active substance(s) will be swallowed and may be absorbed via the gastrointestinal tract.
Oromucosal preparations may contain suitable antimicrobial preservatives and other excipients such as dispersing, suspending, thickening, emulsifying, buffering, wetting, solubilising, stabilising, flavouring and sweetening agents. Solid preparations may in addition contain glidants, lubricants and excipients capable of modifying the release of the active substance(s).
Where applicable, containers for oromucosal preparations 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 preparations for oromucosal use may be distinguished:
PRODUCTION
During the development of an oromucosal preparation containing an antimicrobial preservative, the effectiveness of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. A suitable test method together with the criteria for judging the preservative properties of the formulation are provided in general chapter 5.1.3. Efficacy of antimicrobial preservation.
In the manufacture, packaging, storage and distribution of oromucosal preparations, suitable measures are taken to ensure their microbiological quality; recommendations on this aspect are provided in general chapter 5.1.4. Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use.
In the manufacture of semi-solid and liquid oromucosal preparations containing dispersed particles, measures are taken to ensure a suitable and controlled particle size with regard to the intended use.
TESTS
Uniformity of dosage units
Single-dose oromucosal preparations comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the test 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.
Uniformity of content (2.9.6)
Unless otherwise prescribed or justified and authorised, single-dose oromucosal preparations with a content of active substance less than 2 mg or less than 2 per cent of the total mass comply with test A (compressed and moulded dosage forms) or test B (capsules) for the uniformity of content of single-dose preparations. If the preparation contains more than one active substance, this requirement applies only to those substances that correspond to the above conditions.
Uniformity of mass (2.9.5)
Solid single-dose oromucosal preparations comply with the test for uniformity of mass. If the test for the uniformity of content is prescribed, or justified and authorised, for all active substances, the test for uniformity of mass is not required.
LABELLING
The label states the name of any added preservative.
Gargles
DEFINITION
Gargles are aqueous solutions intended for gargling to obtain a local effect. They are not to be swallowed. They are supplied as ready-to-use solutions or concentrated solutions to be diluted. They may also be prepared from powders or tablets to be dissolved in water before use.
Gargles may contain excipients to adjust the pH which, as far as possible, is neutral.
Mouthwashes
DEFINITION
Mouthwashes are aqueous solutions intended for use in contact with the mucous membrane of the oral cavity. They are not to be swallowed. They are supplied as ready-to-use solutions or concentrated solutions to be diluted. They may also be prepared from powders or tablets to be dissolved in water before use.
Mouthwashes may contain excipients to adjust the pH which, as far as possible, is neutral.
Gingival solutions
DEFINITION
Gingival solutions are liquid, usually multidose preparations intended for administration to the gingivae by means of a suitable applicator.
Oromucosal solutions and oromucosal suspensions
DEFINITION
Oromucosal solutions and oromucosal suspensions are liquid preparations intended for administration to the oral cavity by means of a suitable applicator.
Oromucosal 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.
Semi-solid oromucosal preparations
DEFINITION
Semi-solid oromucosal preparations are hydrophilic gels, creams, ointments or pastes intended for administration to the oral cavity or to a specific part of the oral cavity such as the gingivae (gingival gel, gingival cream, gingival ointment, gingival paste). They may be provided as single-dose preparations.
Semi-solid oromucosal preparations comply with the requirements of the monograph Semi-solid preparations for cutaneous use (0132).
Oromucosal drops, oromucosal sprays and sublingual sprays
DEFINITION
Oromucosal drops, oromucosal sprays and sublingual sprays are solutions, emulsions or suspensions intended for local or systemic effect. They are applied by instillation or spraying into the oral cavity or onto a specific part of the oral cavity such as spraying under the tongue (sublingual spray) or into the throat (oropharyngeal spray).
Emulsions may show evidence of phase separation but are readily redispersed on shaking. Suspensions may show a sediment which is readily dispersed on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be delivered.
Liquid oromucosal sprays are supplied in containers with atomising devices or in pressurised containers having a suitable adaptor, with or without a metering dose valve, which comply with the requirements of the monograph Pressurised pharmaceutical preparations (0523).
The size of the droplets of the spray is such as to localise their deposition in the oral cavity or the throat as intended.
TESTS
Unless otherwise prescribed or justified and authorised, oromucosal drops supplied in single-dose containers, single doses of metered-dose oromucosal sprays and sublingual sprays, all intended for systemic action, comply with the following tests.
OROMUCOSAL DROPS IN SINGLE-DOSE CONTAINERS
Uniformity of dosage units
Oromucosal drops in single-dose containers comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the test for uniformity of mass or uniformity of content shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.
Uniformity of mass
Oromucosal drops that are solutions comply with the following test. Weigh individually the contents of 10 containers emptied as completely as possible, and determine the average mass. Maximum 2 of the individual masses deviate by more than 10 per cent from the average mass and none deviates by more than 20 per cent.
Uniformity of content (2.9.6)
Oromucosal drops that are suspensions or emulsions comply with the following test. Empty each container as completely as possible and carry out the test on the individual contents. They comply with test B of uniformity of content.
METERED-DOSE OROMUCOSAL SPRAYS AND SUBLINGUAL SPRAYS
Uniformity of dosage units
Metered-dose oromucosal sprays and sublingual sprays comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the test for uniformity of mass or the test for uniformity of delivered dose shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.
In the case of metered-dose oromucosal sprays and sublingual sprays that are solutions, proceed as follows. Discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. Weigh the container, discharge once to waste and weigh the container again. Calculate the difference between the 2 masses. Repeat the procedure for a further 9 containers. Determine the mass variation (2.9.40).
Uniformity of mass
Metered-dose oromucosal sprays and sublingual sprays that are solutions comply with the following test. Discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. Weigh the container, discharge once to waste and weigh the container again. Calculate the difference between the 2 masses. Repeat the procedure for a further 9 containers.
The preparation complies with the test if maximum 2 of the individual values deviate by more than 25 per cent from the average value and none deviates by more than 35 per cent.
Uniformity of delivered dose
Metered-dose oromucosal sprays and sublingual sprays that are suspensions or emulsions comply with the following test. Use an apparatus capable of quantitatively retaining the dose leaving the actuator of the atomising device.
Shake the container for 5 s and discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. After 2 s, fire 1 dose of the metered-dose spray into the collecting vessel by actuating the atomising device. Collect the contents of the collecting vessel by successive rinses. Determine the content of active substance in the combined rinses. Repeat the procedure for a further 9 containers.
Unless otherwise justified and authorised, the preparation complies with the test if maximum 1 of the individual contents is outside the limits of 75 per cent to 125 per cent and none is outside the limits of 65 per cent to 135 per cent of the average content.
If 2 or maximum 3 individual contents are outside the limits of 75 per cent to 125 per cent but within the limits of 65 per cent to 135 per cent, repeat the test for 20 more containers. The preparation complies with the test if maximum 3 individual contents of the 30 individual contents are outside the limits of 75 per cent to 125 per cent and none is outside the limits of 65 per cent to 135 per cent of the average content.
Lozenges and pastilles
DEFINITION
Lozenges and pastilles are solid, single-dose preparations intended to be sucked to obtain, usually, a local effect in the oral cavity and the throat. They contain one or more active substances, usually in a flavoured and sweetened base, and are intended to dissolve or disintegrate slowly in the mouth when sucked.
Lozenges are hard preparations prepared by moulding. Pastilles are soft, flexible preparations prepared by moulding of mixtures containing natural or synthetic polymers or gums and sweeteners.
Compressed lozenges
DEFINITION
Compressed lozenges are solid, single-dose preparations intended to be sucked to obtain a local or systemic effect. They are prepared by compression and are often rhomboid in shape.
Compressed lozenges conform with the general definition of tablets.
PRODUCTION
In the manufacture of compressed lozenges, measures are taken to ensure that they possess suitable mechanical strength to resist handling without crumbling or breaking. This may be demonstrated by examining the Friability of uncoated tablets (2.9.7) and the Resistance to crushing of tablets (2.9.8).
TESTS
Dissolution
Unless otherwise justified and authorised, for compressed lozenges intended for a systemic effect, a suitable test is carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in general chapter 2.9.3. Dissolution of solid dosage forms.
Sublingual tablets and buccal tablets
DEFINITION
Sublingual tablets and buccal tablets are solid, single-dose preparations to be applied under the tongue or to the buccal cavity, respectively, to obtain a systemic effect. They are prepared by compression of mixtures of powders or granulations into tablets with a shape suited for the intended use.
Sublingual tablets and buccal tablets conform to the general definition of tablets.
PRODUCTION
In the manufacture of sublingual tablets and buccal tablets, measures are taken to ensure that they possess suitable mechanical strength to resist handling without crumbling or breaking. This may be demonstrated by examining the Friability of uncoated tablets (2.9.7) and the Resistance to crushing of tablets (2.9.8).
TESTS
Dissolution
Unless otherwise justified and authorised, a suitable test is carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in general chapter 2.9.3. Dissolution of solid dosage forms.
Oromucosal capsules
DEFINITION
Oromucosal capsules are soft capsules to be chewed or sucked.
Mucoadhesive preparations
DEFINITION
Mucoadhesive preparations contain one or more active substances intended for systemic absorption through the buccal mucosa over a prolonged period of time. They may be supplied as mucoadhesive buccal tablets, as buccal films or as other mucoadhesive solid or semi-solid preparations. They usually contain hydrophilic polymers, which on wetting with the saliva produce a hydrogel that adheres to the buccal mucosa; in addition, buccal films may dissolve.
Mucoadhesive buccal tablets are prepared by compression and may be single- or multilayer tablets.
Buccal films are single- or multilayer sheets of suitable materials.
PRODUCTION
In the manufacture of mucoadhesive buccal tablets and of buccal films, measures are taken to ensure that they possess suitable mechanical strength to resist handling without crumbling or breaking. For mucoadhesive buccal tablets this may be demonstrated by examining the Friability of uncoated tablets (2.9.7) and the Resistance to crushing of tablets (2.9.8).
TESTS
Dissolution
Unless otherwise justified and authorised, a suitable test is carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in general chapter 2.9.3. Dissolution of solid dosage forms.
Orodispersible films
DEFINITION
Orodispersible films are single- or multilayer sheets of suitable materials, to be placed in the mouth where they disperse rapidly.
PRODUCTION
In the manufacture of orodispersible films, measures are taken to ensure that they possess suitable mechanical strength to resist handling without being damaged.
TESTS
Dissolution
Unless otherwise justified and authorised, a suitable test is carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in general chapter 2.9.3. Dissolution of solid dosage forms.
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