General Notices
(Ph. Eur. monograph 0499)
Granules comply with the requirements of the European Pharmacopoeia. These requirements are reproduced below.
Ph Eur
Requirements for granules to be used for the preparation of oral solutions or suspensions are given in the monograph on Liquid preparations for oral use (0672). Where justified and authorised, the requirements of this monograph do not apply to granules for veterinary use.
DEFINITION
Granules are preparations consisting of solid, dry aggregates of powder particles sufficiently resistant to withstand handling. They are intended for oral administration. Some are swallowed as such, some are chewed and some are dissolved or dispersed in water or another suitable liquid before being administered.
Granules contain one or more active substances with or without excipients and, if necessary, colouring matter authorised by the competent authority and flavouring substances.
Granules are presented as single-dose or multidose preparations. Each dose of a multidose preparation is administered by means of a device suitable for measuring the quantity prescribed. For single-dose granules, each dose is enclosed in an individual container, for example a sachet or a vial.
Where applicable, containers for granules 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 granules may be distinguished:
— effervescent granules;
— coated granules;
— gastro-resistant granules;
— modified-release granules.
PRODUCTION
In the manufacture, packaging, storage and distribution of granules, suitable measures are taken to ensure their microbial quality; recommendations on this aspect are provided in the text on 5.1.4. Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use.
TESTS
Uniformity of dosage units
Single-dose granules 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 granules with a content of active substance less than 2 mg or less than 2 percent 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 which correspond to the above conditions.
Single-dose granules except for coated 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.
Uniformity of mass of delivered doses from multidose containers (2.9.27)
Granules supplied in multidose containers comply with the test.
STORAGE
If the preparation contains volatile ingredients or the contents have to be protected, store in an airtight container.
EFFERVESCENT GRANULES
Requirements for granules to be used for the preparation of oral solutions or suspensions are given in the monograph on Liquid preparations for oral use (0672). Where justified and authorised, the requirements of this monograph do not apply to granules for veterinary use.
DEFINITION
Effervescent granules are uncoated granules generally containing acid substances and carbonates or hydrogen carbonates which react rapidly in the presence of water to release carbon dioxide. They are intended to be dissolved or dispersed in water before administration.
TESTS
Disintegration
Place one dose of the effervescent granules in a beaker containing 200 mL of water R at 15-25 °C; numerous bubbles of gas are evolved. When the evolution of gas around the individual grains ceases, the granules have disintegrated, being either dissolved or dispersed in the water. Repeat the operation on 5 other doses. The preparation complies with the test if each of the 6 doses used disintegrates within 5 min.
STORAGE
In an airtight container.
COATED GRANULES
Requirements for granules to be used for the preparation of oral solutions or suspensions are given in the monograph on Liquid preparations for oral use (0672). Where justified and authorised, the requirements of this monograph do not apply to granules for veterinary use.
DEFINITION
Coated granules are usually multidose preparations and consist of granules coated with one or more layers of mixtures of various excipients.
PRODUCTION
The substances used as coatings are usually applied as a solution or suspension in conditions in which evaporation of the vehicle occurs.
TESTS
Dissolution
A suitable test may be carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in Dissolution test for solid dosage forms (2.9.3).
MODIFIED-RELEASE GRANULES
Requirements for granules to be used for the preparation of oral solutions or suspensions are given in the monograph on Liquid preparations for oral use (0672). Where justified and authorised, the requirements of this monograph do not apply to granules for veterinary use.
DEFINITION
Modified-release granules are coated or uncoated granules which contain special excipients or which are prepared by special procedures, or both, designed to modify the rate, the place or the time at which the active substance or substances are released.
Modified-release granules include prolonged-release granules and delayed-release granules.
PRODUCTION
A suitable test is carried out to demonstrate the appropriate release of the active substance(s).
TESTS
Dissolution
Carry out a suitable test to demonstrate the appropriate release of the active substance(s), for example the test described in Dissolution test for solid dosage forms (2.9.3).
GASTRO-RESISTANT GRANULES
Requirements for granules to be used for the preparation of oral solutions or suspensions are given in the monograph on Liquid preparations for oral use (0672). Where justified and authorised, the requirements of this monograph do not apply to granules for veterinary use.
DEFINITION
Gastro-resistant granules are delayed-release granules that are intended to resist the gastric fluid and to release the active substance(s) in the intestinal fluid. These properties are achieved by covering the granules with a gastro-resistant material (enteric-coated granules) or by other suitable means
PRODUCTION
A suitable test is carried out to demonstrate the appropriate release of the active substance(s).
TESTS
Dissolution
Carry out a suitable test to demonstrate the appropriate release of the active substance(s), for example the test described in Dissolution test for solid dosage forms (2.9.3).
Ph Eur
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