EUROPEAN PHARMACOPOEIA 5.

0 Premixes for medicated feeding stuffs for veterinary use

Where applicable, containers for powders comply with the Where applicable, containers for oral powders comply with
requirements of Materials used for the manufacture of the requirements of Materials used for the manufacture of
containers (3.1 and subsections) and Containers (3.2 and containers (3.1 and subsections) and Containers (3.2 and
subsections). subsections).
PRODUCTION Multidose oral powders require the provision of a measuring
device capable of delivering the quantity prescribed.
In the manufacture of powders for cutaneous application, Each dose of a single-dose powder is enclosed in an
measures are taken to ensure a suitable particle size with individual container, for example a sachet or a vial.
regard to the intended use.
In the manufacture, packaging, storage and distribution of PRODUCTION
powders for cutaneous application, suitable means are taken In the manufacture of oral powders, means are taken to
to ensure their microbial quality ; recommendations on this ensure a suitable particle size with regard to the intended
aspect are provided in the text on Microbiological quality of use.
pharmaceutical preparations (5.1.4). In the manufacture, packaging, storage and distribution
Sterile powders for cutaneous application are prepared of oral powders, suitable means are taken to ensure
using materials and methods designed to ensure sterility and their microbial quality ; recommendations on this aspect
to avoid the introduction of contaminants and the growth are provided in the text on Microbiological quality of
of micro-organisms ; recommendations on this aspect are pharmaceutical preparations (5.1.4).
provided in the text on Methods of preparation of sterile
products (5.1.1). TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed
TESTS or justified and authorised, single-dose oral powders with a
Fineness. If prescribed, the fineness of a powder is content of active substance less than 2 mg or less than 2 per
determined by the sieve test (2.9.12) or another appropriate cent of the total mass comply with test B for uniformity of
method. content of single-dose preparations. If the preparation has
Uniformity of content (2.9.6). Unless otherwise prescribed more than one active substance, the requirement applies
or justified and authorised, single-dose powders for only to those substances which correspond to the above
cutaneous application with a content of active substance conditions.
less than 2 mg or less than 2 per cent of the total mass Uniformity of mass (2.9.5). Single-dose oral powders
comply with test B for uniformity of content of single-dose comply with the test for uniformity of mass of single-dose
preparations. If the preparation has more than one active preparations. If the test for uniformity of content is
substance, the requirement applies only to those substances prescribed for all the active substances, the test for
which correspond to the above conditions. uniformity of mass is not required.
Uniformity of mass (2.9.5). Single-dose powders for Uniformity of mass of delivered doses from multidose
cutaneous application comply with the test for uniformity of containers (2.9.27). Oral powders supplied in multidose
mass of single-dose preparations. If the test for uniformity of containers comply with the test.
content is prescribed for all the active substances, the test
for uniformity of mass is not required. STORAGE
Sterility (2.6.1). Where the label indicates that the If the preparation contains volatile ingredients, or the
preparation is sterile, it complies with the test for sterility. contents have to be protected, store in an airtight container.

LABELLING Effervescent powders

The label states :
Effervescent powders are presented as single-dose or
— that the preparation is for external use,
multidose preparations and generally contain acid
— where applicable, that the preparation is sterile. 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
01/2005:1165
water before administration.
POWDERS, ORAL STORAGE
In an airtight container.
Pulveres perorales
Requirements for powders to be used for the preparation of
01/2005:1037
oral solutions or suspensions are given in the monograph
for Liquid preparations for oral use (0672). Where justified
and authorised, the requirements of this monograph do not PREMIXES FOR MEDICATED FEEDING
apply to oral powders intended for veterinary use. STUFFS FOR VETERINARY USE
DEFINITION
Oral powders are preparations consisting of solid, loose, dry Praeadmixta ad alimenta medicata
particles of varying degrees of fineness. They contain one ad usum veterinarium
or more active substances, with or without excipients and,
if necessary, colouring matter authorised by the competent DEFINITION
authority and flavouring substances. They are generally Mixtures of one or more active substances, usually in
administered in or with water or another suitable liquid. suitable bases, that are prepared to facilitate feeding the
They may also be swallowed directly. They are presented as active substances to animals. They are used exclusively in
single-dose or multidose preparations. the preparation of medicated feeding stuffs.

General Notices (1) apply to all monographs and other texts 617
Preparations for inhalation EUROPEAN PHARMACOPOEIA 5.0

Premixes occur in granulated, powdered, semi-solid or liquid PRODUCTION

form. Used as powders or granules, they are free-flowing During the development of a preparation for inhalation which
and homogeneous ; any aggregates break apart during contains an antimicrobial preservative, the effectiveness
normal handling. Used in liquid form, they are homogeneous of the chosen preservative shall be demonstrated to the
suspensions or solutions which may be obtained from satisfaction of the competent authority. A suitable test
thixotropic gels or structured liquids. The particle size and method together with the criteria for judging the preservative
other properties are such as to ensure uniform distribution properties of the formulation are described in the text on
of the active substance(s) in the final feed. Unless otherwise Efficacy of antimicrobial preservation (5.1.3).
justified and authorised, the instructions for use state that The size of aerosol particles to be inhaled is controlled so
the concentration of a premix in granulated or powdered that a significant fraction is deposited in the lung. The
form is at least 0.5 per cent in the medicated feeding stuff. fine-particle characteristics of preparations for inhalation are
PRODUCTION determined by the method for Aerodynamic assessment of
fine particles (2.9.18).
Active substance. An active substance intended for
In assessing the uniformity of delivered dose of a multidose
incorporation into a medicated premix complies with the
inhaler, it is not sufficient to test a single inhaler.
requirements of the relevant monograph of the European
Manufacturers must substitute procedures which take both
Pharmacopoeia, unless already otherwise justified and
inter- and intra-inhaler dose uniformity into account. A
authorised for existing premixes.
suitable procedure based on the intra-inhaler test would
TESTS be to collect each of the specified doses at the beginning,
middle and end of the number of doses stated on the label
Loss on drying (2.2.32). Unless otherwise justified and from separate inhalers.
authorised, for premixes occurring in granulated or
Pressurised metered-dose inhalers are tested for leakage. All
powdered form, maximum 15.0 per cent, determined on
inhalers are tested for extraneous particulate contamination.
3.000 g by drying in an oven at 100-105 °C for 2 h.
LABELLING
LABELLING
For metered-dose preparations the label states :
The label states :
— the delivered dose, except for preparations for which
— the category of animal for which the premix is intended, the dose has been established as a metered-dose or as
— the instructions for the preparation of the medicated a predispensed-dose,
feeding stuffs from the premix and the basic feed, — where applicable, the number of deliveries from the
— where applicable, the time that must elapse between inhaler to provide the minimum recommended dose,
the cessation of feeding of the medicated feeding stuff — the number of deliveries per inhaler.
and collection of the material intended for human The label states, where applicable, the name of any added
consumption. antimicrobial preservative.

Liquid preparations for inhalation

01/2005:0671 Three categories of liquid preparations for inhalation may
be distinguished :
PREPARATIONS FOR INHALATION A. preparations intended to be converted into vapour,
B. liquid preparations for nebulisation,
Inhalanda C. pressurised metered-dose preparations for inhalation.
Liquid preparations for inhalation are solutions or
DEFINITION dispersions.
Preparations for inhalation are liquid or solid preparations Dispersions are readily dispersible on shaking and they
intended for administration as vapours or aerosols to the remain sufficiently stable to enable the correct dose to be
lung in order to obtain a local or systemic effect. They delivered. Suitable excipients may be used.
contain one or more active substances which may be
dissolved or dispersed in a suitable vehicle. A. PREPARATIONS INTENDED TO BE CONVERTED INTO
Preparations for inhalation may, depending on the type VAPOUR
of preparation, contain propellants, co-solvents, diluents, DEFINITION
antimicrobial preservatives, solubilising and stabilising Preparations intended to be converted into vapour are
agents, etc. These excipients do not adversely affect the solutions, dispersions or solid preparations. They are usually
functions of the mucosa of the respiratory tract or its cilia. added to hot water and the vapour generated is inhaled.
Preparations for inhalation are supplied in multidose or
single-dose containers. When supplied in pressurised B. LIQUID PREPARATIONS FOR NEBULISATION
containers, they comply with the requirements of DEFINITION
the monograph on Pressurised pharmaceutical Liquid preparations for inhalation intended to be converted
preparations (0523). into aerosols by continuously operating nebulisers or
Preparations intended to be administered as aerosols metered-dose nebulisers are solutions, suspensions or
(dispersions of solid or liquid particles in a gas) are emulsions. Suitable co-solvents or solubilisers may be used
administered by one of the following devices : to increase the solubility of the active substances.
— nebuliser, Liquid preparations for nebulisation in concentrated form
for use in continuously operating nebulisers are diluted to
— pressurised metered-dose inhaler, the prescribed volume with the prescribed liquid before use.
— dry-powder inhaler. Liquids for nebulisation may also be prepared from powders.

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