EUROPEAN PHARMACOPOEIA 5.

0 Oromucosal preparations

Uniformity of mass. Nasal drops that are solutions comply The containers are adapted to deliver the product to the site
with the following test : weigh individually the contents of application.
of ten containers emptied as completely as possible, and
determine the average mass. Not more than two of the Nasal washes
individual masses deviate by more than 10 per cent from the
average mass and none deviates by more than 20 per cent. DEFINITION
Metered-dose nasal sprays that are solutions comply with Nasal washes are generally aqueous isotonic solutions
the following test : discharge once to waste. Wait for not intended to cleanse the nasal cavities.
less than 5 s and discharge again to waste. Repeat this Nasal washes intended for application to injured parts or
procedure for a further three actuations. Weigh the mass prior to a surgical operation are sterile.
of the container, discharge once to waste and weigh the
remaining mass of the container. Calculate the difference TESTS
between the two masses. Repeat the procedure for a further Deliverable mass or volume (2.9.28). Nasal washes supplied
nine containers. They comply with the test if not more than in single-dose containers comply with the test.
two of the individual values deviate by more than 25 per
cent from the average value and none deviates by more than Nasal sticks
35 per cent.
Uniformity of content (2.9.6). Nasal drops that are DEFINITION
suspensions or emulsions comply with the following test : Nasal sticks comply with the monograph on Sticks (1154).
empty each container as completely as possible and carry
out the test on the individual content. They comply with 01/2005:1807
test B of uniformity of content.
Uniformity of delivered dose. Metered-dose nasal sprays OROMUCOSAL PREPARATIONS
that are suspensions or emulsions comply with the following
test. Use an apparatus capable of quantitatively retaining Praeparationes buccales
the dose leaving the actuator of the atomising device. This monograph does not apply to dental preparations or
Shake a container for 5 s and discharge once to waste. Wait to preparations such as chewable tablets (0478) , medicated
for not less than 5 s, shake for 5 s and discharge again to chewing gums (1239), oral lyophilisates and other solid
waste. Repeat this procedure for a further three actuations. or semi-solid preparations that are intended to be chewed
After 2 s, fire one dose of the metered-dose nasal spray or dispersed in the saliva before being swallowed. Where
into the collecting vessel by actuating the atomising device. justified and authorised, this monograph does not apply to
Collect the contents of the collecting vessel by successive preparations for veterinary use.
rinses. Determine the content of active substance in the
combined rinses. DEFINITION
Repeat the procedure for a further nine containers. Oromucosal preparations are solid, semi-solid or liquid
preparations, containing one or more active substances
Unless otherwise justified and authorised, the preparation
intended for administration to the oral cavity and/or the
complies with the test if not more than one of the individual
throat to obtain a local or systemic effect. Preparations
contents is outside the limits of 75 per cent to 125 per cent
intended for a local effect may be designed for application to a
and none is outside the limits of 65 per cent and 135 per
specific site within the oral cavity such as the gums (gingival
cent of the average content.
preparations) or the throat (oropharyngeal preparations).
If two or three individual contents are outside the limits Preparations intended for a systemic effect are designed to be
of 75 per cent to 125 per cent but within the limits of absorbed primarily at one or more sites on the oral mucosa
65 per cent to 135 per cent, repeat the test for twenty more (e.g. sublingual preparations). Mucoadhesive preparations
containers. The preparation complies with the test if not are intended to be retained in the oral cavity by adhesion
more than three individual contents of the thirty individual to the mucosal epithelium and may modify systemic drug
contents are outside the limits of 75 per cent to 125 per cent absorption at the site of application. For many oromucosal
and none is outside the limits of 65 per cent to 135 per cent preparations, it is likely that some proportion of the active
of the average content. substance(s) will be swallowed and may be absorbed via the
gastrointestinal tract.
Nasal powders Oromucosal preparations may contain suitable antimicrobial
preservatives and other excipients such as dispersing,
DEFINITION suspending, thickening, emulsifying, buffering, wetting,
Nasal powders are powders intended for insufflation into the solubilising, stabilising, flavouring and sweetening agents.
nasal cavity by means of a suitable device. Solid preparations may in addition contain glidants,
They comply with the requirements of the monograph on lubricants and excipients capable of modifying the release of
Powders for cutaneous application (1166). the active substance(s).
Where applicable, containers for oromucosal preparations
The size of the particles is such as to localise their deposition comply with the requirements for Materials used for the
in the nasal cavity and verified by adequate methods of manufacture of containers (3.1 and subsections) and
particle-size determination. Containers (3.2 and subsections).
Several categories of preparations for oromucosal use may
Semi-solid nasal preparations be distinguished :
DEFINITION — gargles,
Semi-solid nasal preparations comply with the requirements — mouthwashes,
of the monograph on Semi-solid preparations for cutaneous — gingival solutions,
application (0132). — oromucosal solutions and oromucosal suspensions,

General Notices (1) apply to all monographs and other texts 611
Oromucosal preparations EUROPEAN PHARMACOPOEIA 5.0

— semi-solid oromucosal preparations (including for They are supplied as ready-to-use solutions or concentrated
example gingival gel, gingival paste, oromucosal gel, solutions to be diluted. They may also be prepared from
oromucosal paste), powders or tablets to be dissolved in water before use.
— oromucosal drops, oromucosal sprays and sublingual Mouthwashes may contain excipients to adjust the pH which,
sprays (including oropharyngeal sprays), as far as possible, is neutral.
— lozenges and pastilles,
— compressed lozenges, Gingival solutions
— sublingual tablets and buccal tablets, DEFINITION
— oromucosal capsules,
Gingival solutions are intended for administration to the
— mucoadhesive preparations. gingivae by means of a suitable applicator.
PRODUCTION
During the development of an oromucosal preparation Oromucosal solutions and oromucosal
containing an antimicrobial preservative, the effectiveness suspensions
of the chosen preservative shall be demonstrated to the
satisfaction of the competent authority. A suitable test DEFINITION
method together with the criteria for judging the preservative Oromucosal solutions and oromucosal suspensions are
properties of the formulation are provided in 5.1.3 Efficacy liquid preparations intended for administration to the oral
of antimicrobial preservation. cavity by means of a suitable applicator.
In the manufacture, packaging, storage and distribution of Oromucosal suspensions may show a sediment which is
oromucosal preparations, suitable means are taken to ensure readily dispersible on shaking to give a suspension which
their microbiological quality ; recommendations on this remains sufficiently stable to enable the correct dose to be
aspect are provided in the text on Microbiological quality of delivered.
pharmaceutical preparations (5.1.4).
In the manufacture of semi-solid and liquid oromucosal Semi-solid oromucosal preparations
preparations containing dispersed particles, measures are
taken to ensure a suitable and controlled particle size with DEFINITION
regard to the intended use. Semi-solid oromucosal preparations are hydrophilic gels or
TESTS pastes intended for administration to the oral cavity or to a
specific part of the oral cavity such as the gingivae (gingival
Uniformity of content (2.9.6). Unless otherwise prescribed gel, gingival paste). They may be provided as single-dose
or justified and authorised, single-dose preparations with a preparations.
content of active substance less than 2 mg or less than 2 per
cent of the total mass comply with test A (compressed and Semi-solid oromucosal preparations comply with the
moulded dosage forms) or test B (capsules) for the uniformity requirements of the monograph on Semi-solid preparations
of content of single-dose preparations. If the preparation for cutaneous use (0132).
contains more than one active substance, this requirement
applies only to those substances that correspond to the Oromucosal drops, oromucosal sprays and
above conditions. sublingual sprays
Uniformity of mass (2.9.5). Solid single-dose preparations
comply with the test for uniformity of mass. If the test for DEFINITION
the uniformity of content is prescribed, or justified and Oromucosal drops, oromucosal sprays and sublingual sprays
authorised for all active substances, the test for uniformity are solutions, emulsions or suspensions intended for local or
of mass is not required. systemic effect. They are applied by instillation or spraying
into the oral cavity or onto a specific part of the oral cavity
LABELLING such as spraying under the tongue (sublingual spray) or into
The label states the name of any added antimicrobial the throat (oropharyngeal spray).
preservative. Emulsions may show evidence of phase separation but are
readily redispersed on shaking. Suspensions may show a
Gargles sediment which is readily dispersed on shaking to give a
suspension which remains sufficiently stable to enable the
DEFINITION correct dose to be delivered.
Gargles are aqueous solutions intended for gargling to Liquid oromucosal sprays are supplied in containers with
obtain a local effect. They are not to be swallowed. They are atomising devices or in pressurised containers having a
supplied as ready-to-use solutions or concentrated solutions suitable adaptor, with or without a metering dose valve,
to be diluted. They may also be prepared from powders or which comply with the requirements of the monograph on
tablets to be dissolved in water before use. Pressurised pharmaceutical preparations (0523).
Gargles may contain excipients to adjust the pH which, as far The size of the droplets of the spray is such as to localise
as possible, is neutral. their deposition in the oral cavity or the throat as intended.

Mouthwashes TESTS
Unless otherwise prescribed or justified and authorised,
DEFINITION oromucosal drops supplied in single-dose containers,
Mouthwashes are aqueous solutions intended for use in single-doses of metered oromucosal sprays and sublingual
contact with the mucous membrane of the oral cavity, usually sprays intended for systemic action comply with the following
after dilution with water. They are not to be swallowed. tests.

612 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 5.0 Oromucosal preparations

Uniformity of mass. Oromucosal drops that are solutions Compressed lozenges

comply with the following test : determine the individual
masses of the contents of 10 containers emptied as DEFINITION
completely as possible, and calculate the average mass. Not Compressed lozenges are solid, single-dose preparations
more than 2 of the individual masses deviate by more than intended to be sucked to obtain a local or systemic effect.
10 per cent from the average mass and none deviates by They are prepared by compression and are often rhomboid
more than 20 per cent. in shape.
Metered-dose oromucosal sprays and sublingual sprays that Compressed lozenges conform with the general definition
are solutions comply with the following test : discharge once of tablets.
to waste. Wait for not less than 5 s and discharge again to
waste. Repeat this procedure for a further 3 actuations. PRODUCTION
Weigh the mass of the container, discharge once to waste In the manufacture of compressed lozenges, means are
and weigh the remaining mass of the container. Calculate taken to ensure that they possess a suitable mechanical
the difference between the 2 masses. Repeat the procedure strength to resist handling without crumbling or breaking.
for a further 9 containers. The preparation complies with This may be demonstrated by examining the Friability of
the test if not more than 2 of the individual masses deviate uncoated tablets (2.9.7) and the Resistance to crushing of
by more than 25 per cent from the average value and none tablets (2.9.8).
deviates by more than 35 per cent.
TESTS
Uniformity of content (2.9.6). Oromucosal drops that are
Dissolution. For compressed lozenges intended for a
suspensions or emulsions comply with the following test :
systemic effect, a suitable test is carried out to demonstrate
empty each container as completely as possible and carry
the appropriate release of the active substance(s).
out the test on the individual contents. They comply with
test B of uniformity of content.
Uniformity of delivered dose. Metered-dose oromuscal
Sublingual tablets and buccal tablets
sprays and sublingual sprays that are suspensions or DEFINITION
emulsions comply with the following test : use an apparatus
Sublingual tablets and buccal tablets are solid, single-dose
capable of quantitatively retaining the dose leaving the
preparations to be applied under the tongue or to the
actuator of the atomising device.
buccal cavity, respectively, to obtain a systemic effect. They
Shake a container for 5 s and discharge once to waste. Wait are prepared by compression of mixtures of powders or
for not less than 5 s, shake for 5 s and discharge again to granulations into tablets with a shape suited for the intended
waste. Repeat this procedure for a further 3 actuations. use.
After 2 s, fire one dose of the metered-dose oromucosal Sublingual tablets and buccal tablets conform to the general
spray into the collecting vessel by actuating the atomising definition of tablets.
device. Collect the contents of the collecting vessel by
successive rinses. Determine the content of active substance PRODUCTION
in the combined rinses. Repeat the procedure for a further 9 In the manufacture of sublingual tablets and buccal tablets,
containers. Unless otherwise justified and authorised, the means are taken to ensure that they possess suitable
preparation complies with the test if not more than one of mechanical strength to resist handling without crumbling
the individual contents is outside the limits of 75 per cent or breaking. This may be demonstrated by examining the
to 125 per cent and none is outside the limits of 65 per cent Friability of uncoated tablets (2.9.7) and the Resistance to
to 135 per cent of the average content. crushing of tablets (2.9.8).

If 2 or 3 individual contents are outside the limits of 75 per TESTS

cent to 125 per cent but within the limits of 65 per cent Dissolution. Unless otherwise justified and authorised, a
to 135 per cent, repeat the test for 20 more containers. suitable test is carried out to demonstrate the appropriate
The preparation complies with the test if not more than release of the active substance(s).
3 individual contents of the 30 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. Oromucosal capsules
DEFINITION
Oromucosal capsules are soft capsules to be chewed or
Lozenges and pastilles sucked.

DEFINITION
Mucoadhesive preparations
DEFINITION
Lozenges and pastilles are solid, single-dose preparations
intended to be sucked to obtain, usually, a local effect in theMucoadhesive preparations contain one or more active
oral cavity and the throat. They contain one or more active substances intended for systemic absorption through the
substances, usually in a flavoured and sweetened base, and buccal mucosa over a prolonged period of time. They may
are intended to dissolve or disintegrate slowly in the mouth be supplied as mucoadhesive buccal tablets or as other
when sucked. mucoadhesive solid or semi-solid preparations.
Mucoadhesive buccal tablets are prepared by compression
Lozenges are hard preparations prepared by moulding. of mono- or multi-layered tablets. They usually contain
Pastilles are soft, flexible preparations prepared by moulding hydrophilic polymers, which on wetting with the saliva
of mixtures containing natural or synthetic polymers or produce a flexible hydrogel that adheres to the buccal
gums and sweeteners. mucosa.

General Notices (1) apply to all monographs and other texts 613
Parenteral preparations EUROPEAN PHARMACOPOEIA 5.0

PRODUCTION PRODUCTION
In the manufacture of mucoadhesive buccal tablets, means During the development of a parenteral preparation, the
are taken to ensure that they possess suitable mechanical formulation for which contains an antimicrobial preservative,
strength to resist handling without crumbling or breaking. the effectiveness of the chosen preservative shall be
This may be demonstrated by examining the Friability of demonstrated to the satisfaction of the competent authority.
uncoated tablets (2.9.7) and the Resistance to crushing of A suitable test method together with criteria for judging
tablets (2.9.8). the preservative properties of the formulation are provided
under Efficacy of antimicrobial preservation (5.1.3).
TESTS
Parenteral preparations are prepared using materials
Dissolution. Unless otherwise justified and authorised, a and methods designed to ensure sterility and to avoid
suitable test is carried out to demonstrate the appropriate the introduction of contaminants and the growth of
release of the active substance(s). micro-organisms ; recommendations on this aspect are
provided in the text on Methods of preparation of sterile
products (5.1.1).
01/2005:0520 Water used in the manufacture of parenteral preparations
complies with the requirements of water for injections in
PARENTERAL PREPARATIONS bulk stated in the monograph on Water for injections (0169).
TESTS
Parenteralia
Particulate contamination : sub-visible particles (2.9.19).
The requirements of this monograph do not necessarily For preparations for human use, solutions for infusion or
apply to products derived from human blood, to solutions for injection supplied in containers with a nominal
immunological preparations, or radiopharmaceutical content of more than 100 ml comply with the test.
preparations. Special requirements may apply to For preparations for veterinary use, when supplied in
preparations for veterinary use depending on the species containers with a nominal content of more than 100 ml
of animal for which the preparation is intended. and when the content is equivalent to a dose of more than
1.4 ml per kilogram of body mass, solutions for infusion or
DEFINITION solutions for injection comply with the test for particulate
Parenteral preparations are sterile preparations intended for contamination : sub-visible particles.
administration by injection, infusion or implantation into Products for which the label states that the product is to be
the human or animal body. used with a final filter are exempt from these requirements.
Parenteral preparations may require the use of excipients, Sterility (2.6.1). Parenteral preparations comply with the
for example to make the preparation isotonic with blood, to test for sterility.
adjust the pH, to increase solubility, to prevent deterioration
of the active substances or to provide adequate antimicrobial STORAGE
properties but not to adversely affect the intended medicinal Store in a sterile, airtight, tamper-proof container.
action of the preparation or, at the concentrations used, to
cause toxicity or undue local irritation. LABELLING
Containers for parenteral preparations are made as far as The label states :
possible from materials that are sufficiently transparent — the name and concentration of any added antimicrobial
to permit the visual inspection of the contents, except for preservative,
implants and in other justified and authorised cases.
— where applicable, that the solution is to be used in
Where applicable, the containers for parenteral preparations conjunction with a final filter,
comply with the requirements for Materials used for the
manufacture of containers (3.1 and subsections) and — where applicable, that the preparation is free from
Containers (3.2 and subsections). bacterial endotoxins or that it is apyrogenic.
Parenteral preparations are supplied in glass containers
(3.2.1) or in other containers such as plastic containers Injections
(3.2.2, 3.2.2.1 and 3.2.9) and prefilled syringes. The tightness DEFINITION
of the container is ensured by suitable means. Closures
ensure a good seal, prevent the access of micro-organisms Injections are sterile solutions, emulsions or suspensions.
and other contaminants and usually permit the withdrawal They are prepared by dissolving, emulsifying or suspending
of a part or the whole of the contents without removal of the the active substance(s) and any added excipients in Water for
closure. The plastic materials or elastomers (3.2.9) of which injections (0169), in a suitable, sterile non-aqueous liquid or
the closure is composed are sufficiently firm and elastic in a mixture of these vehicles.
to allow the passage of a needle with the least possible Solutions for injection, examined under suitable conditions
shedding of particles. Closures for multidose containers are of visibility, are clear and practically free from particles.
sufficiently elastic to ensure that the puncture is resealed Emulsions for injection do not show any evidence of phase
when the needle is withdrawn. separation. Suspensions for injection may show a sediment
Several categories of parenteral preparations may be which is readily dispersed on shaking to give a suspension
distinguished : which remains sufficiently stable to enable the correct dose
— injections, to be withdrawn.
— infusions, Multidose preparations. Multidose aqueous injections
contain a suitable antimicrobial preservative at an
— concentrates for injections or infusions,
appropriate concentration except when the preparation itself
— powders for injections or infusions, has adequate antimicrobial properties. When it is necessary
— implants. to present a preparation for parenteral use in a multidose

614 See the information section on general monographs (cover pages)