Handbook of
`Pharmaceutical
`Excipients
`Fifth Edition
`
`Edited by
`Raymond C Rowe, Paul J Sheskey
`and Siân C Owen
`
`Mylan Exhibit 1125
`Mylan v. Regeneron, IPR2021-00880
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`Handbook of
`Pharmaceutical Excipients
`
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`Mylan v. Regeneron, IPR2021-00880
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`Handbook of
`Pharmaceutical Excipients
`
`F I F T H E D I T I O N
`
`Edited by
`
`Raymond C Rowe
`BPharm, PhD, DSc, FRPharmS, CChem,
`
`FRSC, CPhys, MInstP
`
`Chief Scientist
`Intelligensys Ltd
`Billingham, UK
`
`Paul J Sheskey
`BSc, RPh
`
`Technical Services Leader
`The Dow Chemical Company
`Midland
`MI, USA
`
`Siaˆn C Owen
`BSc, MA
`
`Development Editor
`Royal Pharmaceutical Society of Great Britain
`London, UK
`
`London . Chicago
`
`Mylan Exhibit 1125
`Mylan v. Regeneron, IPR2021-00880
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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 Pharmacists Association
`2215 Constitution Avenue, NW, Washington, DC 20037-2985, USA
`
`# Pharmaceutical Press and American Pharmacists Association 2006
`
`is a trademark of Pharmaceutical Press
`
`First published 1986
`Second edition published 1994
`Third edition published 2000
`Fourth edition published 2003
`Fifth edition published 2006
`
`Printed in Great Britain by Butler & Tanner, Frome, Somerset
`Typeset by Data Standards Ltd, Frome, Somerset
`
`ISBN 0 85369 618 7 (UK)
`ISBN 1 58212 058 7 (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.–5th ed. / edited by Raymond C.
`Rowe, Paul J. Sheskey, Siaˆ n C. Owen.
`p. ; cm.
`Includes bibliographical references and index.
`ISBN 1-58212-058-7 (USA) – ISBN 0-85369-618-7 (UK)
`1. Excipients–Handbooks, manuals, etc.
`[DNLM: 1. Excipients–Handbooks. 2. Technology, Pharmaceutical–Handbooks.
`QV 735 H236 2006] I. Rowe, Raymond C. II. Sheskey, Paul J. III. Owen, Siaˆ n C.
`IV. American Pharmacists Association.
`
`RS201.E87H36 2006
`0
`.19–dc22
`615
`
`2005028523
`
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`Preface
`
`Pharmaceutical dosage forms contain both pharmacologically
`active compounds and excipients added to aid the formulation
`and manufacture of the subsequent dosage form for adminis-
`tration to patients. 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 concentration
`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 devel-
`oped novel excipient mixtures and new physical forms to
`improve their properties. The Handbook of 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, the third edition
`in 2000 containing 210 monographs and the fourth edition in
`2003 containing 249 monographs. Since 2000, the data has
`also been available on CD-ROM, updated annually, and from
`2004 online. This new printed edition with its companion CD-
`ROM, Pharmaceutical Excipients 5, contains 300 monographs
`compiled by over 120 experts in pharmaceutical formulation or
`excipient manufacture from Australia, Europe, India and the
`USA. 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. Variations 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
`international suppliers included.
`In a systematic and uniform manner, the Handbook of
`Pharmaceutical Excipients collects essential data on the
`physical properties of excipients such as: boiling point, bulk
`and tap density, compression characteristics, hygroscopicity,
`flowability, melting point, moisture content, moisture-absorp-
`tion isotherms, particle size distribution, rheology, specific
`surface area, and solubility. Scanning electron microphoto-
`graphs (SEMs) are also included for many of the excipients. The
`Handbook contains information from various international
`sources and personal observation and comments from mono-
`graph authors, steering committee members, and the editors.
`All of the monographs in the Handbook are thoroughly
`cross-referenced and indexed so that excipients may be
`identified 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 are not
`directly substitutable for each other but, in general, they are
`excipients that have been used for similar purposes in various
`dosage forms.
`The Handbook of Pharmaceutical 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 of Pharmaceutical Excipients will also be of value to
`persons with an interest in the formulation or production of
`confectionery, cosmetics, and food products.
`
`Mylan Exhibit 1125
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