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Flytende preparater til oral bruk
Liquid Preparations for Oral Use (Ph. Eur.)
Praeparationes liquidae peroraliae
Where justified and authorised, the requirements of this monograph do not apply to liquid preparations for oral use intended for veterinary use.
Definition
Liquid preparations for oral use are usually solutions, emulsions or suspensions containing one or more active substances in a suitable vehicle; they may, however, consist of liquid active substances as such (oral liquids).
Some preparations for oral use are prepared by dilution of concentrated liquid preparations, or from powders or granules for the preparation of oral solutions or suspensions, for oral drops or for syrups, using a suitable vehicle.
The vehicle for any preparation for oral use is chosen having regard to the nature of the active substance(s) and to provide organoleptic characteristics appropriate to the intended use of the preparation.
Liquid preparations for oral use may contain suitable antimicrobial preservatives, antioxidants and other excipients such as dispersing, suspending, thickening, emulsifying, buffering, wetting, solubilising, stabilising, flavouring and sweetening agents and colouring matter, authorised by the competent authority.
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 that remains sufficiently stable to enable the correct dose to be delivered.
Where applicable, containers for liquid preparations for oral use comply with the requirements of
Materials used for the manufacture of containers (3.1 and subsections) and
Containers (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.
Production
During development of a preparation for oral use whose formulation contains an antimicrobial preservative, the need for and the efficacy of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. A suitable test method together with criteria for judging the preservative properties of the formulation are provided in general chapter 5.1.3. Efficacy of antimicrobial preservation .
During development, it must be demonstrated that the nominal content can be withdrawn from the container, for liquid preparations for oral use presented in single-dose containers.
In the manufacturing, packaging, storage and distribution of liquid preparations for oral use, suitable measures are taken to ensure their microbial 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 liquid preparations for oral use 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. Solutions, suspensions and emulsions 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 content 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 preparations that are suspensions or emulsions comply with the following test. After shaking, empty each container as completely as possible and carry out the test on the individual contents. They comply with test B for uniformity of content of single-dose preparations.
Uniformity of mass. Single-dose preparations that are solutions comply with the following test: weigh individually the contents of 20 containers, emptied as completely as possible, and determine the average mass. Not more than 2 of the individual masses deviate by more than 10 per cent from the average mass and none deviate by more than 20 per cent.
Dose and uniformity of dose of oral drops. Into a suitable, graduated cylinder, introduce by means of the dropping device the number of drops usually prescribed for one dose, or introduce by means of the measuring device the usually prescribed quantity. The dropping speed does not exceed 2 drops per second. Weigh the liquid, repeat the addition, weigh again and carry on repeating the addition and weighing until a total of 10 masses are obtained. No single mass deviates by more than 10 per cent from the average mass. If the labelling defines a mass, the total of 10 masses does not differ by more than 15 per cent from the nominal mass of 10 doses defined on the labelling. If the labelling defines a volume, measure the total volume of 10 doses. The volume does not differ by more than 15 per cent from the nominal volume of 10 doses defined on the labelling.
Uniformity of mass of delivered doses from multidose containers (2.9.27). Liquid preparations for oral use supplied in multidose containers comply with the test. Oral drops are not subject to the provisions of this test.
Labelling
The label states the name of any added preservative.
Oral solutions, emulsions and suspensions
Definition
Oral solutions, emulsions and suspensions are supplied in single-dose or multidose containers. Each dose from a multidose container is administered by means of a device suitable for measuring the prescribed volume. The device is usually a spoon or a cup for volumes of 5 mL or multiples thereof or an oral syringe for other volumes.
Powders and granules for oral solutions and suspensions
Definition
Powders and granules for the preparation of oral solutions or suspensions are intended to be reconstituted with the prescribed liquid to produce a liquid preparation for oral use. They may contain excipients, in particular to facilitate dispersion or dissolution and to prevent caking.
After dissolution or suspension, they comply with the requirements for oral solutions or oral suspensions, as appropriate.
Tests
Uniformity of dosage units. Single-dose powders and single-dose granules 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 powders and single-dose granules with a content of active substance less than 2 mg or less than 2 per cent of the total mass comply with test B for uniformity of content of single-dose preparations. If the preparation has more than one active substance, the requirement applies only to those substances that correspond to the above conditions.
Uniformity of mass (2.9.5). Single-dose powders and single-dose granules comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active substances, the test for uniformity of mass is not required.
Labelling
The label states:
- the method of preparation of the solution or suspension;
- the conditions and the duration of storage after reconstitution.
Oral drops
Definition
Oral drops are solutions, emulsions or suspensions that are administered in small volumes such as drops by means of a suitable device.
Labelling
The label states the number of drops per millilitre of preparation or per gram of preparation if the dose is measured in drops.
Powders for oral drops
Definition
Powders for the preparation of oral drops are intended to be reconstituted with the prescribed liquid to produce a liquid preparation for oral use. They may contain excipients to facilitate dissolution or suspension in the prescribed liquid or to prevent caking.
After dissolution or suspension, they comply with the requirements for oral drops.
Tests
Uniformity of dosage units. Single-dose powders for oral drops comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the tests 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 powders for oral drops with a content of active substance less than 2 mg or less than 2 per cent of the total mass comply with test B for uniformity of content of single-dose preparations. If the preparation has more than one active substance, the requirement applies only to those substances that correspond to the above conditions.
Uniformity of mass (2.9.5). Single-dose powders for oral drops comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active substances, the test for uniformity of mass is not required.
Syrups
Definition
Syrups are aqueous preparations characterised by a sweet taste and a viscous consistency. They may contain sucrose at a concentration of at least 45 per cent m/m. The sweet taste can also 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. The device is usually a spoon or a cup for volumes of 5 mL or multiples thereof.
Labelling
The label states the name and concentration of the polyol or sweetening agent.
Powders and granules for syrups
Definition
Powders and granules for syrups are intended to be reconstituted with the prescribed liquid to produce a liquid preparation for oral use.. They may contain excipients to facilitate dissolution.
After dissolution, they comply with the requirements for syrups.
Tests
Uniformity of dosage units. Single-dose powders and granules for syrups comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the tests 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 powders and granules for syrups with a content of active substance less than 2 mg or less than 2 per cent of the total mass comply with test B for uniformity of content of single-dose preparations. If the preparation has more than one active substance, the requirement applies only to those substances that correspond to the above conditions.
Uniformity of mass (2.9.5). Single-dose powders and granules for syrups comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active substances, the test for uniformity of mass is not required.
