Handbook of Pharmaceutical Excipients Fifth Edition Edited by Raymond C Rowe, Paul J Sheskey and Siân C Owen Handbook of Pharmaceutical Excipients London . Chicago Handbook of Pharmaceutical Excipients FIFTH EDITION 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 Sia ˆ n C Owen BSc, MA Development Editor Royal Pharmaceutical Society of Great Britain London, UK 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, Sia ˆ 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, Sia ˆ nC. IV. American Pharmacists Association. RS201.E87H36 2006 615 0 .19–dc22 2005028523 Contents International Steering Committee ix Editorial Staff ix Contributors x About the Editors xii New Monographs xiii Related Substances xiv Preface xvi Arrangement xvii Acknowledgments xix Notice to Readers xix Bibliography xx Abbreviations xx Units of Measurement xxii Monographs Acacia 1 Acesulfame Potassium 4 Acetic Acid, Glacial 6 Acetone 8 Acetyltributyl Citrate 10 Acetyltriethyl Citrate 12 Agar 14 Albumin 16 Alcohol 18 Alginic Acid 21 Aliphatic Polyesters 24 Alitame 28 Almond Oil 30 Alpha Tocopherol 32 Aluminum Hydroxide Adjuvant 36 Aluminum Oxide 38 Aluminum Phosphate Adjuvant 40 Aluminum Stearate 42 Ammonia Solution 44 Ammonium Alginate 46 Ascorbic Acid 48 Ascorbyl Palmitate 51 Aspartame 53 Attapulgite 56 Bentonite 58 Benzalkonium Chloride 61 Benzethonium Chloride 64 Benzoic Acid 66 Benzyl Alcohol 69 Benzyl Benzoate 72 Boric Acid 74 Bronopol 76 Butylated Hydroxyanisole 79 Butylated Hydroxytoluene 81 Butylparaben 83 Calcium Alginate 86 Calcium Carbonate 89 Calcium Phosphate, Dibasic Anhydrous 93 Calcium Phosphate, Dibasic Dihydrate 96 Calcium Phosphate, Tribasic 100 Calcium Stearate 102 Calcium Sulfate 105 Canola Oil 108 Carbomer 111 Carbon Dioxide 116 Carboxymethylcellulose Calcium 118 Carboxymethylcellulose Sodium 120 Carrageenan 124 Castor Oil 128 Castor Oil, Hydrogenated 130 Cellulose, Microcrystalline 132 Cellulose, Powdered 136 Cellulose, Silicified Microcrystalline 139 Cellulose Acetate 142 Cellulose Acetate Phthalate 145 Ceratonia 148 Cetostearyl Alcohol 150 Cetrimide 152 Cetyl Alcohol 155 Cetylpyridinium Chloride 157 Chitosan 159 Chlorhexidine 163 Chlorobutanol 168 Chlorocresol 171 Chlorodifluoroethane (HCFC) 174 Chlorofluorocarbons (CFC) 176 Chloroxylenol 180 Cholesterol 182 Citric Acid Monohydrate 185 Colloidal Silicon Dioxide 188 Coloring Agents 192 Copovidone 201 Corn Oil 204 Cottonseed Oil 206 Cresol 208 Croscarmellose Sodium 211 Crospovidone 214 Cyclodextrins 217 Cyclomethicone 222 Denatonium Benzoate 224 Dextrates 226 Dextrin 228 Dextrose 231 Dibutyl Phthalate 234 Dibutyl Sebacate 236 Diethanolamine 238 Diethyl Phthalate 240 Difluoroethane (HFC) 242 Dimethicone 244 Dimethyl Ether 246 Dimethyl Phthalate 248 Dimethyl Sulfoxide 250 Dimethylacetamide 253 Disodium Edetate 255 Docusate Sodium 257 Edetic Acid 260 Erythorbic Acid 264 Erythritol 266 Ethyl Acetate 268 Ethyl Lactate 270 Ethyl Maltol 272 Ethyl Oleate 274 Ethyl Vanillin 276 Ethylcellulose 278 Ethylene Glycol Palmitostearate 283 Ethylene Vinyl Acetate 285 Ethylparaben 287 Fructose 290 Fumaric Acid 293 Gelatin 295 Glucose, Liquid 299 Glycerin 301 Glyceryl Behenate 304 Glyceryl Monooleate 306 Glyceryl Monostearate 308 Glyceryl Palmitostearate 311 Glycofurol 313 Guar Gum 315 Hectorite 318 Heptafluoropropane (HFC) 321 Hexetidine 323 Hydrocarbons (HC) 325 Hydrochloric Acid 328 Hydroxyethyl Cellulose 330 Hydroxyethylmethyl Cellulose 334 Hydroxypropyl Cellulose 336 Hydroxypropyl Cellulose, Low-substituted 341 Hydroxypropyl Starch 344 Hypromellose 346 Hypromellose Acetate Succinate 350 Hypromellose Phthalate 354 Imidurea 359 Inulin 362 Iron Oxides 364 Isomalt 366 Isopropyl Alcohol 371 Isopropyl Myristate 374 Isopropyl Palmitate 376 Kaolin 378 Lactic Acid 381 Lactitol 383 Lactose, Anhydrous 385 Lactose, Monohydrate 389 Lactose, Spray-Dried 396 Lanolin 399 vi Contents Lanolin Alcohols 402 Lanolin, Hydrous 404 Lauric Acid 406 Lecithin 409 Leucine 412 Linoleic Acid 414 Macrogol 15 Hydroxystearate 416 Magnesium Aluminum Silicate 418 Magnesium Carbonate 422 Magnesium Oxide 426 Magnesium Silicate 428 Magnesium Stearate 430 Magnesium Trisilicate 434 Malic Acid 436 Maltitol 438 Maltitol Solution 440 Maltodextrin 442 Maltol 445 Maltose 447 Mannitol 449 Medium-chain Triglycerides 454 Meglumine 457 Menthol 459 Methylcellulose 462 Methylparaben 466 Mineral Oil 471 Mineral Oil, Light 474 Mineral Oil and Lanolin Alcohols 476 Monoethanolamine 478 Monosodium Glutamate 480 Monothioglycerol 482 Myristic Acid 484 Neohesperidin Dihydrochalcone 486 Nitrogen 488 Nitrous Oxide 490 Octyldodecanol 492 Oleic Acid 494 Oleyl Alcohol 496 Olive Oil 498 Palmitic Acid 501 Paraffin 503 Peanut Oil 505 Pectin 507 Petrolatum 509 Petrolatum and Lanolin Alcohols 512 Phenol 514 Phenoxyethanol 517 Phenylethyl Alcohol 519 Phenylmercuric Acetate 521 Phenylmercuric Borate 524 Phenylmercuric Nitrate 526 Phosphoric Acid 530 Polacrilin Potassium 532 Poloxamer 535 Polycarbophil 539 Polydextrose 542 Polyethylene Glycol 545 Polyethylene Oxide 551 Polymethacrylates 553 Poly(methyl vinyl ether/maleic anhydride) 561 Polyoxyethylene Alkyl Ethers 564 Polyoxyethylene Castor Oil Derivatives 572 Polyoxyethylene Sorbitan Fatty Acid Esters 580 Polyoxyethylene Stearates 585 Polyvinyl Acetate Phthalate 589 Polyvinyl Alcohol 592 Potassium Alginate 594 Potassium Benzoate 596 Potassium Bicarbonate 598 Potassium Chloride 600 Potassium Citrate 603 Potassium Hydroxide 605 Potassium Metabisulfite 607 Potassium Sorbate 609 Povidone 611 Propionic Acid 617 Propyl Gallate 619 Propylene Carbonate 622 Propylene Glycol 624 Propylene Glycol Alginate 627 Propylparaben 629 2-Pyrrolidone 633 Raffinose 635 Saccharin 638 Saccharin Sodium 641 Saponite 644 Sesame Oil 646 Shellac 649 Contents vii Simethicone 652 Sodium Acetate 654 Sodium Alginate 656 Sodium Ascorbate 659 Sodium Benzoate 662 Sodium Bicarbonate 665 Sodium Borate 669 Sodium Chloride 671 Sodium Citrate Dihydrate 675 Sodium Cyclamate 678 Sodium Hyaluronate 681 Sodium Hydroxide 683 Sodium Lactate 685 Sodium Lauryl Sulfate 687 Sodium Metabisulfite 690 Sodium Phosphate, Dibasic 693 Sodium Phosphate, Monobasic 696 Sodium Propionate 699 Sodium Starch Glycolate 701 Sodium Stearyl Fumarate 705 Sodium Sulfite 708 Sorbic Acid 710 Sorbitan Esters (Sorbitan Fatty Acid Esters) 713 Sorbitol 718 Soybean Oil 722 Starch 725 Starch, Pregelatinized 731 Starch, Sterilizable Maize 734 Stearic Acid 737 Stearyl Alcohol 740 Sucralose 742 Sucrose 744 Sugar, Compressible 748 Sugar, Confectioner’s 750 Sugar Spheres 752 Sulfobutylether b-Cyclodextrin 754 Sulfuric Acid 758 Sunflower Oil 760 Suppository Bases, Hard Fat 762 Talc 767 Tartaric Acid 770 Tetrafluoroethane (HFC) 772 Thaumatin 775 Thimerosal 777 Thymol 780 Titanium Dioxide 782 Tragacanth 785 Trehalose 788 Triacetin 790 Tributyl Citrate 792 Triethanolamine 794 Triethyl Citrate 796 Vanillin 798 Vegetable Oil, Hydrogenated 800 Water 802 Wax, Anionic Emulsifying 807 Wax, Carnauba 809 Wax, Cetyl Esters 811 Wax, Microcrystalline 813 Wax, Nonionic Emulsifying 815 Wax, White 817 Wax, Yellow 819 Xanthan Gum 821 Xylitol 824 Zein 828 Zinc Acetate 830 Zinc Stearate 832 Appendix I: Suppliers’ Directory 835 Appendix II: List of Excipient ‘E’ Numbers 882 Appendix III: List of Excipient ‘EINECS’ Numbers 884 Appendix IV: List of Excipient Molecular Weights 886 Index 889 viii Contents International Steering Committee Gregory E Amidon Pharmacia Corporation Kalamazoo, MI, USA Graham Buckton University of London London, UK Colin G Cable Western General Hospital Edinburgh, UK Brian A Carlin FMC Biopolymer Princeton, NJ, USA Walter Cook AstraZeneca Loughborough, UK Henk J de Jong Servier International Research Institute Courbevoie, France Stephen Edge DMV International Veghel, The Netherlands Roger T Guest GlaxoSmithKline Ware, Hertfordshire, UK Bruno Hancock Pfizer Inc Groton, CT, USA Stephen W Hoag University of Maryland at Baltimore Baltimore, MD, USA Arthur H Kibbe Wilkes University Wilkes-Barre, PA, USA William J Lambert Eisai Inc Research Triangle Park, NC, USA M Jayne Lawrence King’s College, University of London London, UK John MacLaine Boots Contract Manufacturing Nottingham, UK Colin P McCoy Queens University Belfast Belfast, UK R Christian Moreton Idenix Pharmaceuticals Cambridge, MA, USA Sandeep Nema Pfizer Inc Chesterfield, MO, USA Siaˆn C Owen Royal Pharmaceutical Society of Great Britain London, UK Anthony Palmieri III University of Florida Gainesville, FL, USA Raymond C Rowe Intelligensys Ltd Billingham, UK Shirish A Shah Watson Pharmaceuticals Corona, CA, USA Bob Sherwood JRS Pharma Patterson, NY, USA Paul J Sheskey The Dow Chemical Co Midland, MI, USA Kamalinder K Singh SNDT Women’s University Mumbai, India Paul J Weller Royal Pharmaceutical Society of Great Britain London, UK Tim Wood GlaxoSmithKline Ware, Hertfordshire, UK Mukund Yelvigi Wyeth Research Pearl River, NY, USA Editorial Staf f Editorial Staff of the Pharmaceutical Press: Laurent Y Galichet Louise ME McIndoe Sia ˆ n C Owen Paul J Weller [...]... Handbook of Pharmaceutical Excipients is a comprehensive, 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 pharmaceutical excipients are also used in other applications, the Handbook of Pharmaceutical Excipients will also be... 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 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... 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-absorption isotherms, particle size distribution, rheology, specific surface area, and solubility Scanning electron microphotographs (SEMs) are also included for many of the excipients. .. active compounds and excipients added to aid the formulation and manufacture of the subsequent dosage form for administration 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... ˆ August 2005 Notice to Readers 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 assumed to possess the necessary knowledge to interpret the information that the Handbook contains The Handbook of Pharmaceutical Excipients has no official status and there is no intent, implied... http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/ nmi_list1_e.html (accessed 11 July 2005) Hoepfner E, Reng A, Schmidt PC, eds Fiedler Encyclopedia of Excipients for Pharmaceuticals, Cosmetics and Related Areas Aulendorf, Germany: Editio Cantor, 2002 Japan Pharmaceutical Excipients Council Japanese Pharmaceutical Excipients 2004 Tokyo: Yakuji Nippo, 2004 Japanese Pharmacopeia, 14th edn and supplement Tokyo: Yakuji Nippo, 2001 Kemper... the accepted uses in foods and licensed pharmaceuticals where known However, the status of excipients varies from one nation to another, and appropriate regulatory bodies should be consulted for guidance Section 12, Incompatibilities, describes the reported incompatibilities for the excipient either with other excipients or with active ingredients If an incompatibility is not listed it does not mean... 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... to harmonize standards for excipients Data presented for a particular excipient 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 or electronic versions of the Handbook The reader is asked to send any comments to the Editor, Handbook of Pharmaceutical Excipients, Royal Pharmaceutical... Great Britain, 1 Lambeth High Street, London SE1 7JN, UK, or Editor, Handbook of Pharmaceutical Excipients, American Pharmacists Association, 2215 Constitution Avenue, NW, Washington, DC 20037-2985, USA Bibliography A selection of publications and websites which contain useful information on pharmaceutical excipients is listed below: Ash M, Ash I Handbook of Pharmaceutical Additives, 2nd edn Endicott, . of Pharmaceutical Excipients Fifth Edition Edited by Raymond C Rowe, Paul J Sheskey and Siân C Owen Handbook of Pharmaceutical Excipients London . Chicago Handbook of Pharmaceutical Excipients FIFTH. 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. 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