PIENTS
`THIRD EDITION
`
`
`
`§=©ARTHUR H KIBBE
`
`E D I T E D
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`
`Handbook of
`PHARMACEUTICAL
`EXCIPIENTS
`
`
`
`Third Edition
`
`Edited by
`Arthur H. Kibbe, Ph.D.
`Professor and Chair
`Department of Pharmaceutical Sciences
`Wilkes University School of Pharmacy
`Wilkes-Barre, Pennsylvania
`
`S
`
`American Pharmaceutical Association
`Washington, D.C.
`
`Pharmaceutical Press
`
`London, United Kingdom
`
`UCB Biopharma SPRL (IPR2019-00400)
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`
`
`Published by the American Pharmaceutical Association
`2215 Constitution Avenue NW, Washington, DC 20037-2985, USA
`www.aphanet.org
`and the Pharmaceutical Press
`1 Lambeth High Street, London SEL 7JN, UK
`www.pharmpress.com
`
`© 1986, 1994, 2000 American Pharmaceutical Association and Pharmaceutical Press
`
`First edition 1986
`Second edition 1994
`Third edition 2000
`
`Printed in the United States of America
`
`ISBN: 0-85369-381-1 (UK)
`ISBN: 0-917330-96-X (USA)
`
`Library of Congress Cataloging-in-Publication Data
`Handbook of pharmaceutical excipients / edited by Arthur H. Kibbe.--3rd ed.
`p.
`; cm.
`Includes bibliographical references and index.
`ISBN 0-917330-96-X
`1. Excipients--Handbooks, manuals, etc.
`Pharmaceutical Association.
`[DNLM: 1. Excipients--Handbooks. QV 735 H236 2000]
`RS201.E87 H36 2000
`615'.19--dc21
`
`I. Kibbe, Arthur H. II. American
`
`A catalogue record for this book is available from the British Library.
`
`99-044554
`
`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.
`
`Managing Editor: Melanie Segala
`Copyeditor:
`Paul Gottehrer
`Indexer:
`Lillian Rodberg
`Compositor:
`Roy Barnhill
`Cover Designer:
`Tim Kaage
`
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`Contents
`
`v
`
`138
`
`
`
`Contents
`
`Additions to the Third Edition
`Related Substances
`
`Acknowledgments
`Notice to Readers
`Selected Bibliography
`
`.
`
`Units of Measurement
`
`Acesulfame Potassium
`
`Aliphatic Polyesters
`Alpha Tocopherol
`
`Ascorbyl Palmitate
`
`Benzalkonium Chloride
`Benzethonium Chloride
`
`Benzyl Alcohol
`Benzy] Benzoate
`
`‘
`Butylated Hydroxyanisole
`Butylated Hydroxytoluene
`
`Ze
`
`:
`
`Calcium Carbonate
`Calcium Phosphate, Dibasic Anhydrous
`Calcium Phosphate, Dibasic Dihydrate
`Calcium Phosphate, Tribasic
`Calcium Stearate
`Calcium Sulfate
`
`Carbon Dioxide
`Carboxymethylcellulose Calcium
`Carboxymethylcellulose Sodium
`
`Castor Oil, Hydrogenated
`Cellulose Acetate
`Cellulose Acetate Phthalate
`Cellulose, Microcrystalline
`Cellulose, Powdered
`Cellulose, Silicified Microcrystalline
`Cetostearyl Alcohol
`
`Chlorodifluoroethane (HCFC)
`Chlorofluorocarbons (CFC)
`
`;
`
`,
`
`vil
`ix
`xii
`xiii
`XV
`xvii
`xviii
`XVili
`xix
`XX
`
`1
`3
`5
`7
`10
`13
`18
`21
`25
`27
`30
`33
`36
`38
`41
`44
`46
`49
`51
`53
`56
`60
`63
`68
`70
`73
`77
`79
`83
`85
`87
`91
`94
`96
`99
`102
`107
`110
`112
`114
`117
`121
`126
`129
`132
`134
`
`Cholesterol
`Citric Acid Monohydrate
`Colloidal Silicon Dioxide
`Coloring Agents
`Corn Oil
`Cottonseed Oil
`Cresol
`Croscarmellose Sodium
`Crospovidone
`Cyclodextrins
`Dextrates
`Dextrin
`Dextrose
`Dibutyl Sebacate
`Diethanolamine
`Diethyl! Phthalate
`Difluoroethane (HFC)
`Dimethyl Ether
`Docusate Sodium
`Edetic Acid
`Ethylcetlulose
`Ethyl Maltol
`Ethyl Oleate
`Ethylparaben
`Ethyl Vanillin
`Fructose
`Fumaric Acid
`Gelatin
`Glucose, Liquid
`Glycerin
`Glyceryl Monooleate
`Glyceryl Monostearate
`Glyceryl Palmitostearate
`Glycofurol
`Guar Gum
`Heptafluoropropane (HFC)
`Hydrocarbons (HC)
`Hydrochloric Acid
`Hydroxyethy! Cellulose
`Hydroxypropyl Cellulose
`Hydroxypropyl Cellulose, Low-substituted
`Hydroxypropyl Methylcellulose
`Hydroxypropyl Methylcellulose Phthalate
`Imidurea
`Isopropyl Alcohol
`Isopropyl Myristate
`Isopropyl Palmitate
`Kaolin
`Lactic Acid
`Lactitol
`Lactose
`Lanolin
`Lanolin Alcohols
`Lanolin, Hydrous
`Lecithin
`Magnesium Aluminum Silicate
`Magnesium Carbonate
`Magnesium Oxide
`Magnesium Stearate
`Magnesium Trisilicate
`
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`vi Contents
`
`Malic Acid
`
`Maltitol Solution
`Maltodextrin
`
`Mannitol
`Medium Chain Triglycerides
`Meglumine
`
`zs
`
`Methylcellulose
`Methylparaben
`Mineral Oil
`Mineral Oil, Light
`Mineral Oil and Lanolin Alcohols
`Monoethanolamine
`Nitrogen
`Nitrous Oxide
`Oleic Acid
`
`Peanut Oil
`Petrolatum
`Petrolatum and Lanolin Alcohols
`
`Phenoxyethanol
`Phenylethy! Alcohol
`Phenylmercuric Acetate
`Phenylmercuric Borate
`Phenylmercuric Nitrate
`Polacrilin Potassium
`Poloxamer
`Polydextrose
`Polyethylene Glycol
`Polyethylene Oxide
`Polymethacrylates
`Polyoxyethylene Alkyl Ethers
`Polyoxyethylene Castor Oil Derivatives
`Polyoxyethylene Sorbitan Fatty Acid Esters
`Polyoxyethylene Stearates
`Polyvinyl Alcohol
`Potassium Chioride
`Potassium Citrate
`Potassium Sorbate
`Povidone
`Propylene Carbonate
`Propylene Glycol
`Propylene Glycol Alginate
`Propyl Gailate
`Propyiparaben
`Saccharin
`Saccharin Sodium
`Sesame Oil
`Shellac
`Sodium Alginate
`
`Sodium Ascorbate
`Sodium Benzoate
`Sodium Bicarbonate
`Sodium Chloride
`Sodium Citrate Dihydrate
`Sodium Cyclamate
`Sodium Lauryl Sulfate
`Sodium Metabisulfite
`Sodium Phosphate, Dibasic
`Sodium Phosphate, Monobasic
`Sodium Propionate
`Sodium Starch Glycolate
`Sodium Stearyl Fumarate
`Sorbic Acid
`Sorbitan Esters (Sorbitan Fatty Acid Esters)
`Sorbitol
`Soybean Oil
`Starch
`Starch, Pregelatinized
`Starch, Sterilizable Maize
`Stearic Acid
`Stearyl Alcohol
`Sucrose
`Sugar, Compressible
`Sugar, Confectioner’s
`Sugar Spheres
`Suppository Bases, Hard Fat
`Talc
`Tartaric Acid
`Tetrafluoroethane (HFC)
`Thimerosal
`Titanium Dioxide
`Tragacanth
`Triacetin
`Triethanolamine
`Triethyl Citrate
`Vanillin
`Vegetable Oil, Hydrogenated, Type I
`Water
`Wax, Anionic Emulsifying
`Wax, Carnauba
`Wax, Cetyl Esters
`Wax, Microcrystalline
`Wax, Nonionic Emulsifying
`Wax, White
`Wax, Yellow
`Xanthan Gum
`Xylitol
`Zein
`Zine Stearate
`
`Appendix I: Suppliers’ Directory
`Appendix II: HPE Laboratory Methods
`Index
`
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`
`xviii Notice to Readers
`
`
`
`
`
`Notice to Readers
`
`Selected Bibliography
`
`The Handbook of Pharmaceutical Excipients is a reference
`work containing a compilation of information on the uses and
`properties of pharmaceutical excipients and the reader is as-
`sumed to possess the necessary knowledge to interpret
`the
`information the Handbook contains. The Handbook has no
`official status and there is no intent, implied or otherwise,
`that any of the information presented should constitute stan-
`dards for the substances. The inclusion of an excipient in the
`Handbook, or a description of its use in a particular applica-
`tion, is not intended as an endorsement of that excipient or
`application. Similarly, reports of incompatibilitics or adverse
`reactions to an excipient, in a particular application, may not
`necessarily prevent its use in other applications. Formulators
`should perform suitable experimental studies to satisfy them-
`selves and regulatory bodies that a formulation is efficacious
`and safe to use.
`
`While considerable efforts were made to ensure the accuracy
`of the information presented in the Handbook neither the pub-
`lishers nor the compilers can accept liability for any errors
`or omissions. In particular, the inclusion of a supplier within
`the Suppliers’ Directory is not intended as an endorsement of
`that supplier or its products and similarly the unintentional
`omission of a supplier or product from the directory is not
`intended to reflect adversely on that supplier or its product.
`
`Although diligent effort was made to use as recent compendial
`information as possible, compendia are frequently revised and
`the reader is urged to consult current compendia, or supple-
`ments, for up-to-date information, particularly ‘as efforts are
`currently in progress to harmonize standards for excipients.
`
`The laboratory data presented for a particular excipient re-
`flects only the results of testing a particular batch or sample
`and may not be representative of other batches or samples.
`
`Relevant data and constructive criticism are welcome and may
`be used to assist in the preparation of any. future editions of
`the Handbook. The reader is asked to send any comments to
`the Editor, Handbook of Pharmaceutical Excipients; Royal
`Pharmaceutical Society of Great Britain,
`1 Lambeth High
`Street, London SEL 7JN, UK, or Editor, Handbook of Phar-
`maceutical Excipients, American Pharmaceutical Association,
`2215 Constitution Avenue, N.W., Washington, DC 20037-2985.
`
`A selection of publications which contain information on phar-
`maceutical excipients is listed below:
`
`Banker GS, Rhodes CT, editors. Modern Pharmaceutics, 2nd edi-
`tion. New York, Marcel Dekker Inc., 1990.
`British Pharmacopoeia 1998. London, The Stationery Office,
`1998.
`Budavari S, editor The Merck Index: An Encyclopedia of Chem-
`icals, Drugs, and Biologicals, 12th edition. Whitehouse Sta-
`tion, NJ. Merck & Co., Inc., 1996.
`European Pharmacopoeia, 3rd edition and supplements. Stras-
`bourg, Council of Europe, 1996.
`Florence AT, Salole EG, editors. Formulation Factors in Adverse
`Reactions. London, Butterworth & Co., Ltd., 1990.
`Food and Drug Administration. Inactive Ingredient Guide. Wash-
`ington, DC; FDA, 1996.
`-
`Food Chemicals Codex, 4th edition. Washington, DC, National
`Academy Press, 1996.
`Gennaro AR,editor. Remington: The Science and Practice ofPharmacy,
`19th edition. Easton, PA, Mack Publishing Co., 1995.
`Health and Safety Executive. EH40/98: Occupational exposure
`limits, 1998. Sudbury, Health and Safety Executive, 1998.
`Japan Pharmaceutical Excipients Council. Japanese Pharmaceu-
`tical Excipients 1993. Tokyo, Japan, Yakuji Nippo Ltd., 1994.
`Japanese Pharmacopeia, 13th edition. Tokyo, Japan, Yakuji
`Nippo, Ltd., 1996.
`Lewis RJ, editor. Sax’s Dangerous Properties of Industrial Mate-
`rials, 9th edition. New York, Van Nostrand Reinhold, 1996.
`Lund W,editor. The Pharmaceutical Codex: Principles and Prac-
`tice of Pharmaceutics, 12th edition. London, Pharmaceutical
`Press, 1994.
`Parfitt K, editor. Martindale: The Complete Drug Reference, 32nd
`edition. London, Pharmaceutical Press, 1999.
`Smolinske SC. Handbook of Food, Drug and Cosmetic Excipi-
`ents. Boca Raton, FL, CRC Press Inc., 1992.
`Swarbrick I, Boylan J, editors. Encyclopedia of Pharmaceutical
`Technology, volumes 1-8. New York, Marcel Dekker Inc.,
`1988-1999.
`:
`Sweet DV, editor. Registry of Toxic Effects of Chemical Sub-
`stances. Cincinnati, US Department of Health, 1987.
`United States Pharmacopeia 24 and National Formulary 19 and
`Supplements. Rockville, MD, United States Pharmacopeial
`Convention, Inc., 2000.
`Weiner M, Bernstein IL. Adverse Reactions to Drug Formulation
`Agents: A Handbook of Excipients. New York, Marcel Dekker
`Inc., 1989.
`
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