British Pharmacopoeia 2001
`
`Volume II
`
`Published on the recommendation of the
`Medicines Commission pursuant to the
`Medicines Act 1968 and notified in draft to the
`European Commission in accordance with
`Directive 98/34/EEC
`
`The monographs of the Third Edition of the
`European Pharmacopoeia (1997), as amended
`by the Supplement 2001 published by the
`Council of Europe in September 2000, are
`reproduced either in this edition of the British
`Pharmacopoeia or in the associated edition of
`the British Pharmacopoeia (Veterinary)
`see General Notices, page 3
`
`Effective date: 1 December 2001
`see Notices, page vi
`
`London: The Stationery Office
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 001
`
`

`

`In respect of Great Britain:
`THE DEPARTMENT OF HEALTH
`In respect of Northern Ireland:
`THE DEPARTMENT OF HEALTH, SOCIAL SERVICES AND PUBLIC SAFETY
`
`© Crown Copyright 2001
`
`Published by the Stationery Office under licence from the Controller of Her Majesty's
`Stationery Office for the Department of Health on behalf of the Health Ministers
`
`Printed in the United Kingdom by the Stationery Office Limited under the authority
`and superintendence of the Controller of Her Majesty's Stationery Office and Queen's
`Printer of Acts of Parliament
`
`TJ3544 c40 5/01
`
`This publication is a 'value added' product and falls outside the scope of the Class
`licensing terms offered by HMSO. Applications to reproduce this material should be
`made to the Licensing Division HMSO, St Clements House, 2-16 Colegate, Norwich
`NR3 lBQ or by e-mailing: Anne.Battley@cabinet-office.x.gsi.gov.uk.
`
`First Published 2001
`
`ISBN O 11 322446 X
`
`Laboratory:
`
`Government Buildings
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`Stanmore
`Middlesex HA 7 lA Y
`
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`Fax:
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`
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`www.bpclab.co.uk
`
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`
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`Telephone:
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`Web sites:
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`www.pharmacopoeia.org. uk
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 002
`
`

`

`Contents
`
`Contents of Volume I
`
`NOTICES
`
`PREFACE
`
`BRITISH PHARMACOPOEIA COMMISSION
`
`INTRODUCTION
`Additions, Omissions, Technical Changes, Changes in Title
`
`GENERAL NOTICES
`
`MONOGRAPHS
`
`Medicinal and Pharmaceutical Substances
`
`Contents of Volume II
`
`NOTICES
`GENERAL NOTICES
`MONOGRAPHS
`
`Formulated Preparations: General Monographs
`
`Formulated Preparations: Specific Monographs
`
`Blood Products
`
`Immunological Products
`
`Radiopharmaceutical Preparations
`
`Surgical Materials
`
`INFRARED REFERENCE SPECTRA
`APPENDICES
`
`CONTENTS OF THE APPENDICES
`SUPPLEMENTARY CHAPTERS
`INDEX
`
`PAGE
`
`vi
`
`vii
`
`viii
`
`xm
`xv
`
`1
`
`29
`
`xxiv
`1745
`
`1773
`1825
`2645
`2493
`2577
`2639
`
`Sl
`
`Al
`A3
`A399
`A495
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 003
`
`

`

`FORMULATED PREPARATIONS:
`GENERAL MONOGRAPHS
`
`GLOSSARY
`
`A glossary of tenns relating to fonnulated preparations is
`included in the 3rd edition of the European Phannacopoeia
`[1502}. This glossary is reproduced below.
`
`Ph Eru ____________________ _
`
`The following introductory text provides definitions and/or
`explanations of tenns that may be found in, or used in
`association with, the general monographs on dosage fonns, but
`that are not defined within them. W'here relevant, reference is
`made to other equivalent tenns that may be found in other
`publications or contexts.
`This glossary is given for inf onnation.
`
`Standard Term
`Standard Terms for describing the pharmaceutical form
`of a medicinal product, the routes of administration and
`the containers used have been established by the Euro(cid:173)
`pean Pharmacopoeia Commission and are provided in a
`separate publication on Standard Terms.
`
`Active substance
`The active substance is any component of a medicinal
`product intended to furnish pharmacological activity or
`another direct effect in the diagnosis, treatment or
`prevention of disease, or to affect the structure or
`function of the human or animal body by pharmacolog(cid:173)
`ical means. A medicinal product may contain more than
`one active substance. Equivalent terms: active ingredient,
`drug substance,, medicinal substance.
`
`Excipient
`An excipient is any component, other than the active
`substance(s), present in a medicinal product or used in
`the manufacture of the product. The intended function
`of an excipient is to act as the carrier (vehicle or basis) or
`as a component of the carrier of the active substance(s)
`and, in so doing, to contribute to product attributes such
`as stability, biopharmaceutical profile, appearance and
`patient acceptability and to the ease with which the
`product can be manufactured. Usually, more than one
`excipient is used in the formulation of a medicinal
`product.
`
`Vehicle
`A vehicle is the carrier, composed of one or more excipi(cid:173)
`ents, for the active substance(s) in a liquid preparation.
`
`Basis
`A basis is the carrier, composed of one or more excipi(cid:173)
`ents, for the active substance(s) in semi-solid and solid
`preparations.
`
`Conventional-release dosage forms
`Conventional-release dosage forms are preparations
`showing a release of the active substance(s) which is not
`deliberately modified by a special formulation design
`
`General Monographs
`
`1775
`
`and/or manufacturing method. In the case of a solid
`dosage form, the dissolution profile of the active
`substance depends essentially on its intrinsic properties.
`Equivalent term: immediate-release dosage form.
`
`Modified-release dosage forms
`Modified-release dosage forms are preparations where the
`rate and/or place of release of the active substance(s) is
`different from that of a conventional-release dosage form
`administered by the same route. This deliberate modifi(cid:173)
`cation is achieved by a special formulation design and/or
`manufacturing method. Modified-release dosage forms
`include prolonged-release, delayed-release and pulsatile(cid:173)
`release dosage forms.
`
`Prolonged-release dosage forms
`Prolonged-release dosage forms are modified-release
`dosage forms showing a slower release of the active
`substance(s) than that of a conventional-release dosage
`form administered by the same route. Prolonged-release
`is achieved by a special formulation design and/or
`manufacturing method. Equivalent term: extended(cid:173)
`release dosage form.
`
`Delayed-release dosage forms
`Delayed-release dosage forms are modified-release
`dosage forms showing a release of the active substance(s)
`which is delayed. Delayed release is achieved by a special
`formulation design and/or manufacturing method.
`Delayed-release dosage forms include gastro-resistant
`preparations as defined in the general monographs on
`solid oral dosage forms.
`
`Pulsatile-release dosage forms
`Pulsatile-release dosage forms are modified-release
`dosage forms showing a sequential release of the active
`substance(s). Sequential release is achieved by a special
`formulation design and/or manufacturing method.
`
`Large-volume parenterals
`Infusions and injections supplied in containers with a
`nominal content of more than 100 ml.
`
`Small-volume parenterals
`Infusions and injections supplied in containers with a
`nominal content of 100 ml or less.
`_____________________ Ph Eur
`
`CAPSULES
`
`;t***
`*
`*
`*****
`1/01
`
`Capsules comply with the requirements of the 3rd edition of
`the European Phannacopoeia [0016}. These requirements are
`reproduced below.
`
`Ph Eur ____________________ ~
`
`The requirements of this monograph do not necessarily apply
`to preparations that are presented as capsules intended for use
`other than by oral administration. Requirements for such
`preparations may be found, where appropriate, in other
`general monographs, for example Rectal preparations (1145)
`and Vaginal preparations (1164).
`
`Correspondence between Ph Eur general methods and Appendices of the British Phannacopoeia is shown on page A 9
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 004
`
`

`

`1776 General Monographs
`
`DEFINITION
`Capsules are solid preparations with hard or soft shells of
`various shapes and capacities, usually containing a single
`dose of active substance. They are intended for oral
`administration.
`The capsule shells are made of gelatin or other
`substances, the consistency of which may be adjusted by
`the addition of substances such as glycerol or sorbitol.
`Excipients such as surface-active agents, opaque fillers,
`antimicrobial preservatives, sweeteners, colouring matter
`authorised by the competent authority and flavouring
`substances may be added. The capsules may bear surface
`markings.
`The contents of capsules may be solid, liquid or of a
`paste-like consistency. They consist of one or more active
`substances with or without excipients such as solvents,
`diluents, lubricants and disintegrating agents. The
`contents do not cause deterioration of the shell. The
`shell, however, is attacked by the digestive fluids and the
`contents are released.
`Where applicable, containers for capsules 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 capsules may be distinguished:
`- hard capsules,
`-
`soft capsules,
`- gastro-resistant capsules,
`- modified-release capsules,
`-cachets.
`
`PRODUCTION
`In the manufacture, packaging, storage and distribution
`of capsules, suitable means are taken to ensure their
`microbial quality; recommendations on this aspect are
`provided in the text on Microbiologic·al quality of pharma(cid:173)
`ceutical preparations (5.1.4).
`
`TESTS
`Uniformity of content (2. 9. 6). Unless otherwise
`prescribed or justified and authorised, capsules 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 ingredients which
`correspond to the above conditions.
`Uniformity of mass (2. 9. 5). Capsules 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.
`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).
`Where a dissolution test is prescribed, a disintegration
`test may not be required.
`
`STORAGE
`Store in a well-closed container, at a temperature not
`exceeding 30°C.
`
`LABELLING
`The label states the name of any added antimicrobial
`preservative.
`
`Hard Capsules
`
`DEFINITION
`Hard capsules have shells consisting of two prefabricated
`cylindrical sections one end of which is rounded and
`closed, the other being open.
`
`PRODUCTION
`The active substance(s) usually in solid form (powder or
`granules) are filled into one of the sections which is then
`closed by slipping the other section over it. The security
`of the closure may be strengthened by suitable means.
`
`TESTS
`Disintegration Hard capsules comply with the test for
`disintegration of tablets and capsules (2.9.1). Use water R
`as the liquid medium. When justified and authorised,
`0. 1 M hydrochloric acid or artificial gastric juice R may be
`used as the liquid medium. If the capsules float on the
`surface of the water, a disc may be added. Operate the
`apparatus for 30 min, unless otherwise justified and
`authorised and examine the state of the capsules. The
`capsules comply with the test if all six have disintegrated.
`
`Soft Capsules
`
`DEFINITION
`Soft capsules have thicker shells than those of hard
`capsules. The shells consist of one part and are of various
`shapes.
`
`PRODUCTION
`Soft capsules are usually formed, filled and sealed in one
`operation but for extemporaneous use, the shell may be
`prefabricated. The shell material may contain an active
`substance.
`Liquids may be enclosed directly; solids are usually
`dissolved or dispersed in a suitable vehicle to give a
`solution or dispersion of a paste-like consistency.
`There may be partial migration of the constituents
`from the capsule contents into the shell and vice versa
`because of the nature of the materials and the surfaces in
`contact.
`
`TESTS
`Disintegration Soft capsules comply with the test for
`disintegration of tablets and capsules (2. 9.1). Use water R
`as the liquid medium. When justified and authorised,
`O. lM hydrochloric acid or artificial gastric juice R may be
`used as the liquid medium. Add a disc to each tube.
`Liquid active substances dispensed in soft capsules may
`attack the disc; in such circumstances and where author(cid:173)
`ised, the disc may be omitted. Operate the apparatus for
`30 min, unless otherwise justified and authorised and
`examine the state of the capsules. If the capsules fail to
`comply because of adherence to the discs, repeat the test
`on a further six capsules omitting the discs. The capsules
`comply with the test if all six have disintegrated.
`
`Modified-Release Capsules
`
`DEFINITION
`Modified-release capsules are hard or soft capsules in
`which the contents or the shell or both contain special
`excipients or are prepared by a special process designed
`to modify the rate, the place or the time at which the
`active substance(s) are released.
`
`Correspondence between Ph Eur general methods and Appendices of the British Pharmacopoeia is shown on page A9
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 005
`
`

`

`Modified release capsules include prolonged-release
`capsules and delayed-release capsules.
`
`PRODUCTION
`A suitable test is carried out to demonstrate the appro(cid:173)
`priate release of the active substance(s).
`
`Gastro-Resistant Capsules
`
`DEFINITION
`Gastro-resistant capsules are delayed-release capsules
`that are intended to resist the gastric fluid and to release
`their active substance or substances in the intestinal fluid.
`Usually they are prepared by filling capsules with gran(cid:173)
`ules or with particles covered with a gastro-resistant
`coating or in certain cases, by providing hard or soft
`capsules with a gastro-resistant shell (enteric capsules).
`
`PRODUCTION
`For capsules filled with granules or filled with particles
`covered with a gastro-resistant coating, a suitable test is
`carried out to demonstrate the appropriate release of the
`active substance(s).
`
`TESTS
`Disintegration For capsules with a gastro-resistant shell
`carry out the test for disintegration (2. 9.1) with the
`following modifications. Use O. JM hydrochloric acid as the
`liquid medium and operate the apparatus for 2 h, or
`other such time as may be authorised, without the discs.
`Examine the state of the capsules. The time of resistance
`to the acid medium varies according to the formulation of
`the capsules to be examined. It is typically 2 h to 3 h but
`even with authorised deviations it must not be less than
`1 h. No capsule shows signs of disintegration or rupture
`permitting the escape of the contents. Replace the acid by
`phosphate buffer solution pH 6. 8 R. When justified and
`authorised, a buffer solution of pH 6.8 with added
`pancreas powder (for example, 0.35 g of pancreas
`powder R per 100 ml of buffer solution) may be used.
`Add a disc to each tube. Operate the apparatus for
`60 min and examine the state of the capsules. If the
`capsules fail to comply because of adherence to the discs,
`repeat the test on a further six capsules omitting the
`discs. The capsules comply with the test if all six have
`disintegrated.
`Dissolution For capsules prepared from granules or
`particles already covered with a gastro-resistant coating, a
`suitable test is carried out 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).
`
`Cachets
`
`DEFINITION
`Cachets are solid preparations consisting of a hard shell
`containing a single dose of one or more active substances.
`The cachet shell is made of unleavened bread usually
`from rice flour and consists of two prefabricated flat
`cylindrical sections. Before administration, the cachets
`are immersed in water for a few seconds, placed on the
`tongue and swallowed with a draught of water.
`
`LABELLING
`The label states the method of administration of the
`cachets.
`____________________ Ph Eur
`
`General Monographs
`
`1777
`
`Capsules of the British Pharmacopoeia
`In addition to the above requirements of the European
`Pharmacopoeia, the following statements apply to those
`capsules that are the subject of an individual monograph in
`the British Pharmacopoeia.
`
`When presented as granules the contents of the requisite
`number of capsules should be mixed and powdered
`before performing the Assay and tests described in the
`monograph.
`Content of active ingredient in capsules The range
`for the content of active ingredient stated in the mono(cid:173)
`graph is based on the requirement that 20 capsules, or
`such other number as may be indicated in the mono(cid:173)
`graph, are used in the Assay. In the circumstances where
`20 capsules cannot be obtained, a smaller number, which
`must not be less than 5, may be used, but to allow for
`sampling errors the tolerances are widened in accordance
`with Table I.
`The requirements of Table I apply when the stated
`limits are 90 to 110%. For limits other than 90 to 110%,
`proportionately smaller or larger allowances should be
`made.
`Disintegration For those Hard Capsules or Soft
`Capsules for which a requirement for Dissolution is
`included in the individual monograph, the requirement
`for Disintegration does not apply.
`Uniformity of content Details of the analytical method
`to be employed for determining the content of active
`ingredient may be included in certain monographs.
`Unless otherwise stated in the monograph the limits are
`as given in test B for uniformity of content, Appendix
`XIIH.
`Any capsules that when examined individually show a
`gross deviation from the prescribed or stated content are
`not official.
`Labelling The label states (1) the quantity of the active
`ingredient contained in each Capsule; (2) the date after
`which the Capsules are not intended to be used; (3) the
`conditions under which the Capsules should be stored.
`
`The following capsules are the subject of an individual mono(cid:173)
`graph in the British Pharmacopoeia.
`Acebutolol Capsules
`Amantadine Capsules
`Amoxicillin Capsules
`Ampicillin Capsules
`Azapropazone Capsules
`Bromocriptine Capsules
`Calcitriol Capsules
`Cefaclor Caspules
`Cefadroxil Capsules
`Cefalexin Capsules
`Cefradine Capsules
`Chloramphenicol Capsules
`Chlordiazepoxide Capsules
`Clindamycin Capsules
`Clobazam Capsules
`Clofazimine Capsules
`Clofibrate Capsules
`Clomethiazole Capsules
`Clomipramine Capsules
`Cloxacillin Capsules
`
`Correspondence between Ph Eur general methods and Appendices of the British Pharmacopoeia is shown on page A9
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 006
`
`

`

`1778 General Monographs
`
`Co-beneldopa Capsules
`Co-danthrusate Capsules
`Co-fluampicil Capsules
`Demeclocycline Capsules
`Dextropropoxyphene Capsules
`Disopyramide Capsules
`Disopyramide Phosphate Capsules
`Docusate Capsules
`Dosulepin Capsules/Dothiepin Capsules
`Doxepin Capsules
`Doxycycline Capsules
`Erythromycin Estolate Capsules
`Estramustine Phosphate Capsules
`· Ethosuximide Capsules
`Etodolac Capsules
`Etoposide Capsules
`Fenbufen Capsules
`Ferrous Fumarate Capsules
`Flucloxacillin Capsules
`Fluoxetine Capsules
`Flurazepam Capsules
`Gemfibrozil Capsules
`Halibut-liver Oil Capsules
`Haloperidol Capsules
`Hydroxycarbamide Capsules/Hydroxyurea Capsules
`Indometacin Capsules
`Isotretinoin Capsules
`Ketoprofen Capsules
`Levodopa Capsules
`Lincomycin Capsules
`Lomustine Capsules
`Loperamide Capsules
`Lymecycline Capsules
`Mefenamic Acid Capsules
`Metyrapone Capsules
`Mexiletine Capsules
`Naftidrofuryl Capsules
`Nifedipine Capsules
`Nortriptyline Capsules
`Oxytetracycline Capsules
`Pentazocine Capsules
`Peppermint Oil Capsules, Gastro-resistant
`Phenoxybenzamine Capsules
`Phenytoin Capsules
`Piroxicam Capsules
`Propranolol Capsules, Prolonged-release
`Rifampicin Capsules
`Tetracycline Capsules
`Triamterene Capsules
`Ursodeoxycholic Acid Capsules
`
`MEDICATED CHEWING GUMS
`
`*****
`*
`*
`*****
`corrected 1 IO 1
`
`Medicated Chewing Gums comply with the requirements of
`the 3rd edition of the European Phannacopoeia [1239]. These
`requirements are reproduced after the heading 'Definition'
`below.
`
`Ph Eur ____________________ _
`
`DEFINITION
`Medicated chewing gums are s~lid, single-dose prepara(cid:173)
`tions with a base consisting mainly of gum that are
`intended to be chewed but not swallowed.
`They contain one or more active substances which are
`released by chewing. After dissolution or dispersion of
`the active substances in saliva, chewing gums are
`intended to be used for:
`-
`local treatment of mouth diseases,
`-
`systemic delivery after absorption through the buccal
`mucosa or from the gastrointestinal tract.
`
`PRODUCTION
`Medicated chewing gums are made with a tasteless
`masticatory gum base that consists of natural or synthetic
`elastomers. They may contain other excipients such as
`fillers, softeners, sweetening agents, flavouring
`substances, stabiliser and plasticisers and authorised
`colouring matter.
`Medicated chewing gums are manufactured by
`compression or by softening or melting the gum bases
`and adding successively the other substances. In the latter
`case, chewing gums are then further processed to obtain
`the desired gum presentation. The medicated chewing
`gums may be coated, for example, if necessary to protect
`from humidity and light.
`Unless otherwise justified and authorised, a suitable
`test is carried out to demonstrate the appropriate release
`of the active ingredient( s).
`In the manufacture, packaging, storage and distribu(cid:173)
`tion of medicated chewing gums, suitable means must be
`taken to ensure their microbial quality; recommendations
`related to this aspect are provided in the general chapter
`on Microbiological quality of phannaceutical preparations
`(5.1.4).
`
`TESTS
`Uniformity of content (2. 9. 6). Unless otherwise
`prescribed or justified and authorised, medicated chewiQg
`gums with a content of active ingredient less than 2 mg
`or less than 2 per cent of the total mass comply with test
`A for uniformity of content of single-dose preparations. If
`the preparation contains more than one active substance,
`the requirement applies only to those active subs·tances
`which correspond to the above conditions.
`Uniformity of mass (2.9.5). Uncoated medicated
`chewing gums and, unless otherwise justified and author(cid:173)
`ised, coated medicated chewing gums 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.
`
`STORAGE
`Store uncoated medicated chewing gums protected from
`humidity and light.
`____________________ PhEur
`
`Correspondence between Ph Eur general methods and Appendices of the British Phannacopoeia is shown on page A9
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 007
`
`

`

`LIQUIDS FOR CUTANEOUS
`APPLICATION
`LIQUID PREPARATIONS FOR
`CUTANEOUS APPLICATION
`
`1/01
`
`Liquids for Cutaneous Application comply with the require(cid:173)
`ments of the 3rd edition of the European Pharmacopoeia
`[09 2 7} for Liquid Preparations for Cutaneous Application.
`These requirements are reproduced below.
`
`Ph Eur ____________________ _
`
`W'here justified and authorised, the requirements of this
`monograph do not apply to liquid preparations for cutaneous
`application intended for systemic use.
`DEFINITION
`Liquid preparations for cutaneous application are
`preparations of a variety of viscosities intended to be
`applied to the skin (including the scalp) or nails in order
`to obtain a local action or transdermal activity. They are
`solutions, emulsions or suspensions which may contain
`one or more active substances in a suitable vehicle. They
`may contain suitable antimicrobial preservatives, antioxi(cid:173)
`dants and other excipients such as stabilisers, emulsifiers
`and thickeners.
`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 which is sufficiently stable to enable a
`homogeneous preparation to be delivered.
`Where applicable, containers for liquid preparations for
`cutaneous application comply with the requirements of
`Materials used for the manufacture of containers (3.1 and
`subsections) and Containers (3.2 and subsections).
`When liquid preparations for cutaneous application are
`dispensed in pressurised containers, the containers
`comply with the requirements of the monograph on
`Pressurised pharmaceutical preparations ( 0523).
`Preparations specifically intended for use on severely
`injured skin are sterile.
`Several categories of liquid preparations for c.utaneous
`application may be distinguished:
`-shampoos,
`-
`cutaneous foams.
`
`PRODUCTION
`During the development of a liquid preparation for
`cutaneous application, the formulation for which
`contains an antimicrobial preservative, the effectiveness
`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 the text on
`Efficacy of antimicrobial preservation (5.1.3).
`In the manufacture, packaging, storage and distribu(cid:173)
`tion of liquid preparations for cutaneous application,
`suitable means are taken to ensure their microbial
`quality; recommendations on this aspect are provided in
`the text on Microbiological quality of pharmaceutical
`preparations (5.1. 4).
`Sterile liquid preparations for cutaneous application are
`prepared using materials and methods designed to ensure
`sterility and to avoid the introduction of contaminants
`and the growth of micro-organisms; recommendations on
`
`General Monographs
`
`1779
`
`this aspect are provided in the text on Methods of prepara(cid:173)
`tion of sterile products (5.1.1).
`In the manufacture of liquid preparations for cutaneous
`application containing dispersed particles, measures are
`taken to ensure a suitable and controlled particle size
`with regard to the intended use.
`
`TESTS
`Deliverable mass or volume (2.9.28). Liquid prepara(cid:173)
`tions for cutaneous application supplied in single-dose
`containers comply with the test.
`Sterility (2. 6.1). Where the label indicates that the
`preparation is sterile, it complies with the test for sterility.
`
`STORAGE
`Store in a well-closed container. If the preparation is
`sterile, store in a sterile, airtight, tamper-proof container.
`
`LABELLING
`The label states:
`the name of any added antimicrobial preservative,
`-
`- where applicable, that the preparation is sterile.
`
`Shampoos
`DEFINITION
`Shampoos are liquid or, occasionally semi-solid prepara(cid:173)
`tions intended for application to the scalp and subse(cid:173)
`quent washing away with water. Upon rubbing with
`water they usually form a foam.
`They are emulsions, suspensions or solutions. Shampoos
`normally contain surface active agents.
`
`Cutaneous Foams
`DEFINITION
`Cutaneous foams comply with the requirements of the
`monograph on Medicated foams (1105).
`____________________ Ph Eur
`
`Liquids for Cutaneous Application of the
`British Pharmacopoeia
`In addition to the above requirements of the European
`Pharmacopoeia, the following statements apply to any applic(cid:173)
`ation, collodion, liniment, lotion or paint that is the subject of
`an individual monograph in the British Pharmacopoeia and
`to the solutions listed below.
`
`APPLICATIONS
`Labelling The label states (1) that the Application is
`intended for external use only; (2) the date after which
`the Application is not intended to be used; (3) the condi(cid:173)
`tions under which the Application should be stored; ( 4)
`the directions for using the Application; (5) any special
`precautions associated with the use of the Application.
`
`COLLODIONS
`Definition Collodions are Liquids for Cutaneous Appli(cid:173)
`cation, usually containing Pyroxylin in a mixture of Ether
`and Ethanol. When they are allowed to dry, a flexible
`film is formed at the site of application.
`Storage Collodions should be stored at temperatures not
`exceeding 25° and remote from fire.
`
`Correspondence between Ph Eur general methods and Appendices of the British Pharmacopoeia is shown on page A9
`
`Par Pharm., Inc.
`Exhibit 1046
`Page 008
`
`

`

`1780 General Monographs
`
`Labelling The label states (1) that the Collodion is
`intended for external use only; (2) the date after which
`the Collodion is not intended to be used; (3) the condi(cid:173)
`tions under which the Collodion should be stored; ( 4)
`the directions for using the Collodion; (5) any special
`precautions associated with the use of the Collodion.
`
`LINIMENTS
`Definition Liniments are Liquids for Cutaneous Appli(cid:173)
`cation that are intended to be applied to the unbroken
`skin with friction.
`Storage Certain plastic containers, such as those made
`from polystyrene, are unsuitable for Liniments.
`Labelling The label states (1) the names and concentra(cid:173)
`tions of the active ingredients; (2) that the Liniment is
`intended for external use only; (3) if appropriate, that the
`contents of the container should be shaken before use;
`( 4) the date after which the Liniment is not intended to
`be used; (5) the conditions under which the Liniment
`should be stored; (6) the directions for using the Lini(cid:173)
`ment; (7) any special precautions associated with the use
`of the Liniment.
`
`LOTIONS
`Definition Lotions are Liquids for Cutaneous Applica(cid:173)
`tion that are intended to be applied to the unbroken skin
`without friction.
`Labelling The label states ( 1) the names and concentra(cid:173)
`tions of the active ingredients; (2) that the Lotion is
`intended for external use only; (3) that the Lotion should
`be shaken before use; ( 4) the date after which the Lotion
`is not intended to be used; (5) the conditions under
`which the Lotion should be stored; (6) the directions for
`using the Lotion; (7) any special precautions associated
`with the use of the Lotion.
`
`NAIL SOLUTIONS
`Labelling The label states (1) the name and concentra(cid:173)
`tion of the active ingredient; (2) that the Nail Solution is
`intended for external use only; (3) the date after which
`the Nail Solution is not intended to be used; ( 4) the
`conditions under which the Nail Solution should be
`stored; (5) the directions for using the Nail Solution; (6)
`any special precautions associated with use of the Nail
`Solution.
`
`PAINTS
`Definition Paints are solutions or dispersions of one or
`more active ingredients. They are intended for applica(cid:173)
`tion to the skin or, in some cases, mucous membranes.
`Storage Paints should be kept in airtight containers.
`Labelling The label states (1) the names and concentra(cid:173)
`tions of the active ingredients; (2) the date after which
`the Paint is not intended to be used; (3) the conditions
`under which the Paint should be stored; ( 4) the direc(cid:173)
`tions for using the Paint; (5) any special precautions
`associated with the use of the Paint.
`
`The following liquids for cutaneous application are the subject
`of an individual monograph in the British Pharmacopoeia.
`Applications
`Benzyl Benzoate Application
`Betamethasone Valerate Scalp Application
`Minoxidil Scalp Application
`
`Selenium Sµlphide Scalp Application
`Collodions
`Flexible Collodion
`Salicylic Acid Collodion
`Liniments
`Methyl Salicylate Liniment
`White Liniment
`Lotions
`Benzoyl Peroxide Lotion
`Betamethasone Valerate Lotion
`Calamine Lotion
`Carbaryl Lotion
`Crotamiton Lotion
`Zinc Sulphate Lotion
`Nail Solutions
`Tioconazole Nail Solution
`Paints
`Podophyllin Paint, Compound
`Solutions
`Note: Certain formulated preparations other than the
`ones listed below are the subject of an individual mono(cid:173)
`graph in the British Pharmacopoeia with the title Solu(cid:173)
`tion. As confirmed by the absence of a cross reference to
`the general monograph for Liquids for Cutaneous Appli(cid:173)
`cation, such solutions are outside the scope of this
`general monograph.
`Adrenaline Solution/Epinephrine Solution
`Cetrimide Solution
`Chlorinated Lime and Boric Acid Solution
`Chloroxylenol Solution
`Iodine Solution, Alc