Handbook of
`Pha rmaceutica I Exc i Tents
`p
`
`FOURTH EDITION
`
`Edited by
`
`Raymond C Rowe
`BPharm, PhD, DSc, fRPharmS, CChem, FRSC, CPhys, MlnstP
`
`Senior Principal Scienfist
`
`AshaZeneca
`
`Macclesfield, UK
`
`Paul J Sheskey
`BSc, RPh
`
`Technical Service Leader
`
`Water Soluble Polymers RB~D
`
`The Dow Chemital Company
`
`Midland
`
`MI, USA
`
`Paul J Weller
`BSc, MSc, CChem, MRSC
`
`Publisher —Science and Practice
`Royal Pharmaceutical Society of Great Britain
`
`London, UK
`
`h
`London ~ Chicago Pharmaceutical Press
`
`0
`
`American
`Pharmaceutical
`Association
`
`Page 1
`
`SHIRE EX. 2064
`KVK v. SHIRE
`IPR2018-00290
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`

`

`Published by the Pharmaceutical Press
`Publications division of the Royal Pharmaceutical Society of Great Britain
`
`1 Lambeth High Street, London SE1 7JN, UK
`100 South Atkinson Road, Suite 206, Grayslake, IL 60030-7820, USA
`
`and the American Pharmaceufical Assaiation
`2215 Constitution Avenue NW, Washington, DC 20037-2985, USA
`
`C Pharmaceutical Press and American Pharmaceutical Association 2003
`
`(PP/ is a trade mark of Pharmaceutical Press
`
`First edition published 1986
`Second edition published 1994
`Third edition published 2000
`Fourth edition published 2003
`
`Text design by Barker Hilsdon, Lyme Regis
`Typeset by Bibliocraft Ltd, Dundee
`Printed in Great Britain by The Bath Press, Bath
`
`ISBN 0 85369 4?2 9 (iJIC)
`ISBN 1 58212 022 6 (USA)
`
`All rights reserved. No part of this publication may be
`reproduced, stored in a retrieval system, or transmitted in any
`form or by any means, without the prior written permission
`of the copyright holder.
`The publisher makes no representation, express or implied,
`with regard to the accuracy of the information contained in
`this book and cannot accept any legal responsibility or
`liability for any errors or omissions that may be made.
`
`A catalogue record for this book is available from the British Library
`
`Library of Congress Cataloging-in-Publication Data
`Handbook of pharmaceutical excipients.-4th ed. /edited by Rar'mond C.
`Rowe, Paul J. Sheskey, Paul J. DG'eller.
`p. ; cm.
`Includes bibliographical references and index.
`ISBN 1-58212-022-6 (alk. paper) —ISBN 0-85369-472-9 (alk. paper)
`1. Excipients—Handbooks, manuals, etc.
`[DNLM: 1. Excipients—Handbooks. QV 735 H236 2003] I. Rowe, Raymond
`C. II. Sheskey, Paul J. III. a'eller, Paul J.
`
`RS201.E87H36 2003
`615'.19~c21
`
`2003002641
`
`Page 2
`
`

`

`Preface
`
`PHARMACEUTICAL DOSAGE FORMS contain both pharma-
`cologically active compounds and excipients added to aid the
`formulation and manufacture of the subsequent dosage form
`for administration to parients. Indeed, the properties of the final
`dosage form (i.e. its bioavailability and stability) are, for the
`most part, highly dependent on the excipients chosen, their
`concentrarion and interaction with both the active compound
`and each other. No longer can excipients be regarded simply as
`inert or inactive ingredients, and a detailed knowledge not only
`of the physical and chemical properties but also of the safety,
`handling and regulatory status of these materials is essential for
`formulators throughout the world. In addition, the growth of
`novel forms of delivery has resulted in an increase in the number
`of the excipients being used and suppliers of excipients have
`developed novel excipient mixtures and new physical Eorms to
`improve their properties. The Handbook o f Pharmaceutical
`Excipients has been conceived as a systematic, comprehensive
`resource of information on all of these topics.
`The first edition of the Handbook was published in 1986
`and contained 145 monographs. This was followed by the
`second edition in 1994 containing 203 monographs and the
`third edition in 2000 containing 210 monographs. Since the
`release of the third edition two CD-ROM editions have also
`been released: Pharmaceutical Excipients 2000 included the
`same material as the third edirion, and Pharmaceutical
`Excipients 2001, which included 20 new monographs.
`This new printed edition with its companion CD-ROM
`contains 250 monographs authored by experts in pharmaceu-
`tical formulation or excipient manufacture from around the
`world. All the monographs have been reviewed and revised in
`the light of current knowledge. There has been a greater
`emphasis on including published data from primary sources
`although some data from laboratory projects included in
`previous editions have been retained where relevant. Varia-
`tions in test methodology can have significant effects on the
`data generated (especially in the case of the compactability of
`an excipient), and thus cause confusion. As a consequence, the
`editors have been more selective in including data relating to the
`physical properties of an excipient. However, comparative data
`that show differences between either source or batch of a
`specific excipient 'have been retained as this was considered
`relevant to the behavior of a material in practice. The Suppliers
`Directory (Appendix I) has also been completely updated with
`many more internarional suppliers included.
`In a systemaric and uniform manner, the Handbook o f
`Pharmacez~tical Excipients collects essenrial data on the physi-
`cal properties of excipients such as: boiling point, bulk and tap
`density, compression characteristics, hygroscopicity, flow-
`ability, melting point, moisture content, moisture-absorption
`isotherms, particle size distribution, rheology, specific surface
`area, and solubility. Scanning electron microphotographs
`(SEMs) are also included for many of the excipients. The
`H. andbook contains information from various internarional
`sources and personal observation and comments from
`monograph authors, steering committee members, and the
`editors.
`
`All of the monographs in the Handbook aze thoroughly
`cross-referenced and indexed so that excipients may be idenri-
`fied by either a chemical, a nonproprietary, or a trade name.
`Most monographs list related substances to help the formulator
`to develop a list of possible materials for use in a new dosage
`form or product. Related substances aze not directly substitu
`table for each other but, in general, they aze excipients that have
`been used for similar purposes in various dosage forms.
`The Handbook of Phar~naceutica~ Excipients is a compre-
`hensive, uniform guide to the uses, properties, and safety of
`pharmaceutical excipients, and is an essential reference source
`for those involved in the development, production, control, or
`regulation of pharmaceutical preparations. Since many phar-
`maceutical excipients are also used in other applications, the
`Handbook o f Pharmaceutical Excipients will also be of value to
`persons with an interest in the formularion or production of
`confectionery, cosmetics, and food products.
`
`Arrangement
`
`The information consists of monographs that are divided into
`22 sections to enable the reader to find the information of
`interest easily. Although it was originally intended that each
`monograph contain only information about a single excipient, it
`rapidly became clear that some substances or groups of sub-
`stances should be discussed together. This gave rise to such
`monographs as `Coloring Agents' and `Hydrocarbons'. In addi-
`tion, some materials have more than one monograph depending
`on the physical characteristics of the material, e.g. Starch versus
`Pregelatinized Starch. Regardless of the complexity of the
`monograph they are all divided into 22 sections as follows:
`
`1 Nonproprietary Names
`2 Synonyms
`3 Chemical Name and CAS Registry Number
`4 Empirical Formula and Molecular Weight
`5 Structural Formula
`6 Functional Category
`7 Applications in Pharmaceutical Formulation or Technology
`8 Description
`9 Pharmacopeial Specifications
`10 Typical Properties
`11 Stability and Storage Conditions
`12 IncomparibIliues
`13 Method of Manufacture
`14 Safety
`15 Handling Precautions
`16 Regulatory Status
`17 Related Substances
`18 Comments
`19 Specific References
`20 General References
`21 Authors
`22 Date of Revision
`
`Descriptions of the sections appear below with information
`from an example monograph if needed.
`
`xVil
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`Page 3
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