Liquid preparations for oral use EUROPEAN PHARMACOPOEIA 7.0

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LIQUID PREPARATIONS FOR ORAL USE

Praeparationes liquidae peroraliaeWhere justified and authorised, the requirements of thismonograph do not apply to liquid preparations for oral useintended for veterinary use.

DEFINITIONLiquid preparations for oral use are usually solutions, emulsionsor suspensions containing one or more active substances ina suitable vehicle ; they may, however, consist of liquid activesubstances used as such (oral liquids).Some preparations for oral use are prepared by dilution ofconcentrated liquid preparations, or from powders or granulesfor the preparation of oral solutions or suspensions, for oraldrops or for syrups, using a suitable vehicle.The vehicle for any preparations for oral use is chosen havingregard to the nature of the active substance(s) and to provideorganoleptic characteristics appropriate to the intended useof the preparation.Liquid preparations for oral use may contain suitableantimicrobial preservatives, antioxidants and other excipientssuch as dispersing, suspending, thickening, emulsifying,buffering, wetting, solubilising, stabilising, flavouring andsweetening agents and colouring matter, authorised by thecompetent authority.Emulsions may show evidence of phase separation but arereadily redispersed on shaking. Suspensions may show asediment, which is readily dispersed on shaking to give asuspension that remains sufficiently stable to enable thecorrect dose to be delivered.Where applicable, containers for liquid preparations for oraluse comply with the requirements of Materials used forthe manufacture of containers (3.1 and subsections) andContainers (3.2 and subsections).Several categories of preparations may be distinguished ; oral solutions, emulsions and suspensions ; powders and granules for oral solutions and suspensions ; oral drops ; powders for oral drops ; syrups ; powders and granules for syrups.

PRODUCTIONDuring development of a preparation for oral use whoseformulation contains an antimicrobial preservative, theneed for and the efficacy of the chosen preservative shall bedemonstrated to the satisfaction of the competent authority.A suitable test method together with criteria for judging thepreservative properties of the formulation are provided in thetext on Efficacy of antimicrobial preservation (5.1.3).During development, it must be demonstrated that the nominalcontent can be withdrawn from the container, for liquidpreparations for oral use presented in single-dose containers.In the manufacturing, packaging, storage and distribution ofliquid preparations for oral use, suitable measures are takento ensure their microbial quality ; recommendations on thisaspect are provided in the text on Microbiological quality ofpharmaceutical preparations (5.1.4).In the manufacture of liquid preparations for oral use containingdispersed particles, measures are taken to ensure a suitable andcontrolled particle size with regard to the intended use.

TESTS

Uniformity of dosage units. Solutions, suspensions andemulsions in single-dose containers comply with the testfor uniformity of dosage units (2.9.40) or, where justified

and authorised, with the test for uniformity of content oruniformity of mass shown below. Herbal drugs and herbal drugpreparations present in the dosage form are not subject to theprovisions of this paragraph.

Uniformity of content (2.9.6). Unless otherwise prescribedor justified and authorised, single-dose preparations that aresuspensions comply with the following test. After shaking,empty each container as completely as possible and carry outthe test on the individual contents. They comply with test B foruniformity of content of single-dose preparations.

Uniformity of mass. Single-dose preparations that are solutionsor emulsions comply with the following test : weigh individuallythe contents of 20 containers, emptied as completely as possible,and determine the average mass. Not more than 2 of theindividual masses deviate by more than 10 per cent from theaverage mass and none deviate by more than 20 per cent.

Dose and uniformity of dose of oral drops. Into a suitablegraduated cylinder, introduce by means of the droppingdevice the number of drops usually prescribed for one dose,or introduce by means of the measuring device the usuallyprescribed quantity. The dropping speed does not exceed 2drops per second. Weigh the liquid, repeat the addition, weighagain and carry on repeating the addition and weighing until atotal of 10 masses are obtained. No single mass deviates by morethan 10 per cent from the average mass. The total of 10 massesdoes not differ by more than 15 per cent from the nominal massof 10 doses. If necessary, measure the total volume of 10 doses.The volume does not differ by more than 15 per cent from thenominal volume of 10 doses.

Uniformity of mass of delivered doses from multidosecontainers (2.9.27). Liquid preparations for oral use suppliedin multidose containers comply with the test. Oral drops arenot subject to the provisions of this test.

LABELLINGThe label states the name of any added antimicrobialpreservative.

Oral solutions, emulsions and suspensionsDEFINITIONOral solutions, emulsions and suspensions are supplied insingle-dose or multidose containers. Each dose from a multidosecontainer is administered by means of a device suitable formeasuring the prescribed volume. The device is usually a spoonor a cup for volumes of 5 mL or multiples thereof or an oralsyringe for other volumes.

Powders and granules for oral solutions andsuspensions

DEFINITIONPowders and granules for the preparation of oral solutionsor suspensions generally conform to the definitions in themonographs on Oral powders (1165) or Granules (0499) asappropriate. They may contain excipients, in particular tofacilitate dispersion or dissolution and to prevent caking.After dissolution or suspension, they comply with therequirements for oral solutions or oral suspensions, asappropriate.

TESTS

Uniformity of dosage units. Single-dose powders andsingle-dose granules comply with the test for uniformity ofdosage units (2.9.40) or, where justified and authorised, withthe tests for uniformity of content and/or uniformity of massshown below. Herbal drugs and herbal drug preparationspresent in the dosage form are not subject to the provisionsof this paragraph.

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

EUROPEAN PHARMACOPOEIA 7.0 Nasal preparations

Uniformity of content (2.9.6). Unless otherwise prescribed orjustified and authorised, single-dose powders and single-dosegranules with a content of active substance less than 2 mgor less than 2 per cent of the total mass comply with test Bfor uniformity of content of single-dose preparations. Ifthe preparation has more than one active substance, therequirement applies only to those substances that correspondto the above conditions.

Uniformity of mass (2.9.5). Single-dose powders andsingle-dose granules comply with the test for uniformity of massof single-dose preparations. If the test for uniformity of contentis prescribed for all the active substances, the test for uniformityof mass is not required.

LABELLINGThe label states : the method of preparation of the solution or suspension ; the conditions and the duration of storage after

reconstitution.

Oral dropsDEFINITIONOral drops are solutions, emulsions or suspensions that areadministered in small volumes such as drops by the means ofa suitable device.

LABELLINGThe label states the number of drops per millilitre of preparationor per gram of preparation if the dose is measured in drops.

Powders for oral dropsDEFINITIONPowders for the preparation of oral drops generally conformto the definition of Oral powders (1165). They may containexcipients to facilitate dissolution or suspension in theprescribed liquid or to prevent caking.After dissolution or suspension, they comply with therequirements for oral drops.

TESTS

Uniformity of dosage units. Single-dose powders for oral dropscomply with the test for uniformity of dosage units (2.9.40) or,where justified and authorised, with the tests for uniformity ofcontent and/or uniformity of mass shown below. Herbal drugsand herbal drug preparations present in the dosage form arenot subject to the provisions of this paragraph.

Uniformity of content (2.9.6). Unless otherwise prescribed orjustified and authorised, single-dose powders for oral dropswith a content of active substance less than 2 mg or less than2 per cent of the total mass comply with test B for uniformityof content of single-dose preparations. If the preparation hasmore than one active substance, the requirement applies onlyto those substances that correspond to the above conditions.

Uniformity of mass (2.9.5). Single-dose powders for oral dropscomply with the test for uniformity of mass of single-dosepreparations. If the test for uniformity of content is prescribedfor all the active substances, the test for uniformity of mass isnot required.

SyrupsDEFINITIONSyrups are aqueous preparations characterised by a sweettaste and a viscous consistency. They may contain sucrose at aconcentration of at least 45 per cent m/m. The sweet taste canalso be obtained by using other polyols or sweetening agents.Syrups usually contain aromatic or other flavouring agents.Each dose from a multidose container is administered by means

of a device suitable for measuring the prescribed volume. Thedevice is usually a spoon or a cup for volumes of 5 mL ormultiples thereof.

LABELLINGThe label states the name and concentration of the polyol orsweetening agent.

Powders and granules for syrupsDEFINITIONPowders and granules for syrups generally conform to thedefinitions in the monograph on Oral powders (1165) orGranules (0499). They may contain excipients to facilitatedissolution.After dissolution, they comply with the requirements for syrups.

TESTS

Uniformity of dosage units. Single-dose powders and granulesfor syrups comply with the test for uniformity of dosage units(2.9.40) or, where justified and authorised, with the tests foruniformity of content and/or uniformity of mass shown below.Herbal drugs and herbal drug preparations present in thedosage form are not subject to the provisions of this paragraph.

Uniformity of content (2.9.6). Unless otherwise prescribedor justified and authorised, single-dose powders and granulesfor syrups with a content of active substance less than 2 mgor less than 2 per cent of the total mass comply with test Bfor uniformity of content of single-dose preparations. Ifthe preparation has more than one active substance, therequirement applies only to those substances that correspondto the above conditions.

Uniformity of mass (2.9.5). Single-dose powders and granulesfor syrups comply with the test for uniformity of mass ofsingle-dose preparations. If the test for uniformity of content isprescribed for all the active substances, the test for uniformityof mass is not required.

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NASAL PREPARATIONS

NasaliaDEFINITIONNasal preparations are liquid, semi-solid or solid preparationsintended for administration to the nasal cavities to obtaina systemic or local effect. They contain one or more activesubstances. Nasal preparations are as far as possiblenon-irritating and do not adversely affect the functions of thenasal mucosa and its cilia. Aqueous nasal preparations areusually isotonic and may contain excipients, for example, toadjust the viscosity of the preparation, to adjust or stabilisethe pH, to increase the solubility of the active substance, or tostabilise the preparation.Nasal preparations are supplied in multidose or single-dosecontainers, provided, if necessary, with a suitable administrationdevice, which may be designed to avoid the introduction ofcontaminants.Unless otherwise justified and authorised, aqueous nasalpreparations supplied in multidose containers contain a suitableantimicrobial preservative in an appropriate concentration,except where the preparation itself has adequate antimicrobialproperties.Where applicable, the containers comply with the requirementsof Materials used for the manufacture of containers (3.1 andsubsections) and Containers (3.2 and subsections).Several categories of nasal preparations may be distinguished: nasal drops and liquid nasal sprays ; nasal powders ;

General Notices (1) apply to all monographs and other texts 719

17-DosageForms-EtocLiquid preparations for oralusePraeparationes liquidae peroraliaeDEFINITIONPRODUCTIONTESTSUniformity of dosageunits. Solutions, suspensions and emulsionsUniformity of content (2.9.6). Unless otherwise prescribed or juUniformity of mass. Single-dose preparations that are solutions Dose and uniformity ofdose of oral drops. Into a suitable graduUniformity of mass of delivered doses from multidose containers

LABELLINGDEFINITIONDEFINITIONTESTSUniformity of dosageunits. Single-dose powders and single-dose Uniformity of content (2.9.6). Unless otherwise prescribed or juUniformity of mass (2.9.5). Single-dose powders and single-dose

LABELLINGDEFINITIONLABELLINGDEFINITIONTESTSUniformity of dosageunits. Single-dose powders for oral drops cUniformity of content (2.9.6). Unless otherwise prescribed or juUniformity of mass (2.9.5). Single-dose powders for oral drops c

DEFINITIONLABELLINGDEFINITIONTESTSUniformity of dosageunits. Single-dose powders and granules forUniformity of content (2.9.6). Unless otherwise prescribed or juUniformity of mass (2.9.5). Single-dose powders and granules for

Nasal preparationsNasaliaDEFINITION