The International Pharmacopoeia

Fourth Edition First Supplement

The fourth edition of the International Pharmacopoeia comprises two main volumes published in 2006. This first Supplement includes a collection of recommended procedures for analysis and specifications for the determination of pharmaceutical substances, excipients and dosage forms that is intended to serve as source material for reference or adaptation by any WHO Member State wishing to establish pharmaceutical requirements. New monographs New monographs are included for five antiretroviral substances, for sixteen antiretroviral dosage forms including two fixed-dose combination preparations, for one antimalarial dosage form and for six antituberculosis dosage forms including 2-, 3-, and 4-component fixed-dose preparations. Such specifications support the joint UNICEFWHO-UN Prequalification project, managed by WHO. In developing these monographs WHO has worked closely with manufacturers, national authorities and national quality control laboratories. New general monographs for Liquid preparations for oral use and Oral powders are included to support the relevant specific dosage-form monographs. The monograph for Liquid preparations for oral use highlights that such preparations are often the dosage form of choice for paediatric use. This general monograph also includes a statement on Safety concerns in the section on Manufacture. This draws attention to the importance of ensuring the quality of starting materials. Failure to ensure that starting materials are of the required quality can have very serious consequences. Revision In parallel with the development of the new monograph for Doxycycline capsules, the published monographs for Doxycycline hyclate and Doxycycline tablets have been revised and replacement texts are included in this supplement. A requirement for dissolution has been included for several monographs. Infrared Reference spectra Many monographs in The International Pharmacopoeia include an identification test using infrared spectroscopy; these tests usually allow comparison either with a spectrum obtained from the ICRS or with a reference spectrum. The majority of the infrared reference spectra are newly available and published within this supplement. Chromatographic tests In chromatographic tests included within the monographs of The International Pharmacopoeia, the type of chromatographic column, column packing or TLC plate to be used is stated but reference to commercial sources of these supports is not given. When a draft monograph is circulated for comment, the particular column that was used during the development of a liquid chromatographic test is provided for information (usually in a footnote to the text). This information is now provided on the WHO Medicines website to assist analysts with respect to choice of column for those monographs recently introduced into the Pharmacopoeia.
First Supplement 2008, 365 pages [E, F*, S*] ISBN 978 92 4 154742 0 CHF/US$ 70.00 In developing countries: CHF/US$ 49.00 Order no. 11501639

New monographs included in the First Supplement

Pharmaceutical substances Abacavir sulfate Efavirenz Lamivudine Stavudine Zidovudine Dosage forms General monographs Liquid preparations for oral use Oral powders Specific monographs Abacavir oral solution Abacavir sulfate tablets Didanosine oral powder Didanosine liquid for oral use, paediatric Didanosine tablets Doxycycline capsules Isoniazid and ethambutol hydrochloride tablets Lamivudine oral solution Lamivudine tablets Nelfinavir Mesilate oral powder Nelfinavir Mesilate tablets Rifampicin capsules Rifampicin tablets Rifampicin and isoniazid tablets Rifampicin, isoniazid and pyrizinamide tablets Rifampicin, isoniazid, pyrizinamide and ethambutol hydrochloride tablets Saquinavir mesilate capsules Stavudine capsules Zidovudine capsules Zidovudine oral solution Zidovudine intravenous infusion Zidovudine and Lamivudine tablets Zidovudine Lamivudine and Abacavir tablets Dosage forms General monographs Liquid preparations for oral use Oral powders Specific monographs Abacavir oral solution Abacavir sulfate tablets Didanosine oral powder Didanosine liquid for oral use, paediatric Didanosine tablets Doxycycline capsules Isoniazid and ethambutol hydrochloride tablets Lamivudine oral solution Lamivudine tablets Nelfinavir Mesilate oral powder Nelfinavir Mesilate tablets Rifampicin capsules Rifampicin tablets Rifampicin and isoniazid tablets Rifampicin, isoniazid and pyrizinamide tablets Rifampicin, isoniazid, pyrizinamide and ethambutol hydrochloride tablets Saquinavir mesilate capsules Stavudine capsules Zidovudine capsules Zidovudine oral solution Zidovudine intravenous infusion Zidovudine and Lamivudine tablets Zidovudine Lamivudine and Abacavir tablets

CD-ROM International Pharmacopoeia. Fourth Edition

Including First Supplement This CD-ROM incorporates all new monographs, amendments and additions as published in the First Supplement into the previous electronic version of the 4th edition. Thus it will replace the former version in a user friendly way.

2008, CD-ROM [E] ISBN 978 92 4 154443 7 CHF/US$ 200.00 In developing countries: CHF/US$ 140.00 Order no. 19900037

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The International Pharmacopoeia, 4th edition

Contents Preface History Acknowledgements General Notices Abbreviations and symbols Units of measurement Names, symbols and relative atomic masses of certain elements International chemical reference substances Monographs The fourth edition includes all the monographs in the third edition together with new monographs listed overleaf. The monographs are presented in the following sections: Pharmaceutical Substances (all monographs for active ingredients and excipients in one alphabetical sequence) Dosage Forms General monographs: Capsules, Ophthalmic preparations, Parenteral preparations, Suppositories, Tablets, Topical Semi-solid dosage forms Individual monographs: (all individual monographs in alphabetical order) Radiopharmaceuticals Methods of analysis 1. Physical and Physicochemical Methods 2. Chemical methods 3. Biological methods 4. Methods for materials of plant origin 5. Pharmaceutical technical procedures Reagents, Test Solutions and Volumetric Solutions Supplementary Information Index

The International Pharmacopoeia

Fourth Edition
This new edition consolidates the texts of the five separate volumes of the third edition. In preparing this consolidated edition the opportunity has been taken to review the General notices of the Pharmacopoeia. Certain additions and amendments have been made to the notices in order to clarify the interpretation of the Pharmacopoeia and to facilitate application of the requirements by the user. The opportunity has also been taken to improve certain aspects of the layout and format of the publication. In this Fourth edition all the monograph texts are brought together in one section and the method texts in another. Each of these major sections are divided into appropriate sub-sections and the method texts are numbered for ease of cross-reference. New monographs for the following antiretroviral substances are published in the Fourth edition: didanosine, indinavir sulfate, nelfinavir mesilate, nevirapine, ritonavir, saquinovir, and saquinovir mesilate. Revision of the current monograph for Oral rehydration salts has been carried out to conform to the modified formula published in the 13th Model List of Essential Medicines (WHO Technical Report Series, No. 920, 2003) and in the WHO Model Formulary 2004. The revised formula has a reduced sodium chloride and glucose content providing a solution with a reduced osmolarity of 245 mOsm/l. Due to the improved effectiveness of the reduced osmolarity ORS solution, especially for children with acute, non-cholera diarrhoea, WHO and UNICEF now recommend that countries use and manufacture this formulation in place of the previously recommended ORS, i.e. the one published in the third edition of The International Pharmacopoeia, which has a total osmolarity of 311 mOsm/l.

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International Chemical Reference Substances (ICRS)
To coincide with the publication of the updated fourth edition of The International Pharmacopoeia, the WHO Collaborating Centre for Chemical Reference Substances is offering a special 50 % discount to National Authorities on orders for the International Chemical Reference Substances (ICRS) needed to support the International Pharmacopoeia monographs. This offer is valid until 31 December 2008 for one order per national control laboratory with a maximum order of 10 vials per laboratory. For ordering information, please visit http://www.apl.apoteket.se/who.

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Method texts that have been updated include, for example, the text on high performance liquid chromatography [HPLC]. This has been revised to clarify certain technical terms and to add advice on adjustment of chromatographic conditions, as recommended by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in October 2004. (see table of contents page 4.)

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2006, 2 volumes 1500 pages [E] ISBN 978 92 4 156301 7 CHF/US$ 400.00 In developing countries: CHF/US$ 200.00 Order no. 11500639