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 Siaˆn 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, Siaˆn 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, Siaˆn C. IV. American Pharmacists Association. RS201.E87H36 2006 6150 .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 Siaˆ n 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 Staff Editorial Staff of the Pharmaceutical Press: Laurent Y Galichet Louise ME McIndoe Siaˆn C Owen Paul J Weller Contributors O AbuBaker Pfizer Inc Ann Arbor, MI, USA KS Alexander University of Toledo Toledo, OH, USA LV Allen International Journal of Pharmaceutical Compounding Edmond, OK, USA GE Amidon Pharmacia Corporation Kalamazoo, Michigan, USA GP Andrews The Queen’s University of Belfast Belfast, UK NA Armstrong Harpenden, Hertfordshire, UK ME Aulton De Montford University Leicester, UK S Behn AstraZeneca Macclesfield, UK M Bond Danisco Sweeteners Ltd Redhill, Surrey, UK CG Cable Western General Hospital Edinburgh, UK E Cahill AstraZeneca Macclesfield, UK W Camarco ISP Corp Wayne, NJ, USA WG Chambliss University of Mississippi University, MS, USA RK Chang Shire Laboratory Rockville, MD, USA R Chen Pfizer Inc Groton, CT, USA JH Chu Pfizer Inc Groton, CT, USA JH Collett University of Manchester Manchester, UK JT Colvin Pfizer Inc Groton, CT, USA W Cook AstraZeneca Loughborough, UK DQM Craig The University of East Anglia Norwich, UK TC Dahl Gilead Sciences Foster City, CA, USA A Day AstraZeneca Loughborough, UK HJ de Jong Servier International Research Institute Courbevoie, France SP Denyer University of Cardiff Cardiff, UK X Duriez Roquette Fre`res Lestrem, France S Edge DMV International Veghel, The Netherlands K Fowler Schering-Plough Healthcare Products Memphis, TN, USA SO Freers Grain Processing Corporation Muscatine, IA, USA B Fritzsching Palatinit GmbH Mannheim, Germany G Frunzi Bristol-Myers Squibb New Brunswick, NJ, USA LY Galichet Royal Pharmaceutical Society of Great Britain London, UK SR Goskonda Sunnyvale, CA, USA JL Gray The Queen’s University of Belfast Belfast, UK RT Guest GlaxoSmithKline Ware, Hertfordshire, UK RR Gupta SNDT Women’s University Mumbai, India VK Gupta Tyco HealthCare Mallinckrodt St Louis, MO, USA G Haest Cargill Cerestar BVBA Mechelen, Belgium BC Hancock Pfizer Inc Groton, CT, USA RJ Harwood Bensalem, PA, USA S Hem Purdue University West Lafayette, IN, USA L Hendricks Rhodia Inc Cranbury, NJ, USA SE Hepburn Bristol Royal Infirmary Bristol, UK NA Hodges University of Brighton Brighton, UK JT Irwin Perrigo Corporation MI, USA BR Jasti University of the Pacific Stockton, CA, USA R Johnson AstraZeneca Loughborough, UK DS Jones The Queen’s University of Belfast Belfast, UK AS Kearney GlaxoSmithKline King-of-Prussia, PA, USA SW Kennedy Morflex Inc Greensboro, NC, USA VL Kett The Queen’s University of Belfast Belfast, UK AH Kibbe Wilkes University Wilkes-Barre, PA, USA V King Rhodia Inc Cranbury, NJ, USA PB Klepak Reheis Inc Berkley Heights, NJ, USA JJ Koleng University of Texas at Austin Austin, TX, USA K Kussendrager DMV International Veghel, The Netherlands WJ Lambert Eisai Inc Research Triangle Park, NC, USA BA Langdon Pfizer Inc Groton, CT, USA MJ Lawrence King’s College, University of London London, UK JC Lee Cellegy San Jose´, CA, USA MG Lee Medicines and Healthcare products Regulatory Agency London, UK X Li University of the Pacific Stockton, CA, USA EB Lindblad Brenntag Biosector Frederikssund, Denmark O Luhn Palatinit GmbH Mannheim, Germany PE Luner Pfizer Inc Groton, CT, USA HJ Mawhinney The Queen’s University of Belfast Belfast, UK CP McCoy The Queen’s University of Belfast Belfast, UK OS McGarvey The Queen’s University of Belfast Belfast, UK JW McGinity University of Texas at Austin Austin, TX, USA LME McIndoe Royal Pharmaceutical Society of Great Britain London, UK LA Miller Pfizer Inc Groton, CT, USA RW Miller Bristol-Myers Squibb New Brunswick, NJ, USA J-P Mittwollen BASF Aktiengesellschaft Ludwigshafen, Germany RC Moreton Idenix Pharmaceuticals Cambridge, MA, USA G Mosher CyDex Inc Lenexa, KS, USA C Mroz Colorcon Ltd Dartford, Kent, UK MP Mullarney Pfizer Inc Groton, CT, USA S Murdande Pfizer Inc Groton, CT, USA RA Nash St John’s University Jamaica, NY, USA S Nema Pfizer Inc Chesterfield, MO, USA SC Owen Royal Pharmaceutical Society of Great Britain London, UK A Palmieri University of Florida Gainesville, FL, USA D Parsons ConvaTec Ltd Clwyd, UK Y Peng University of Tennessee Memphis, TN, USA JD Pipkin CyDex Inc Lenexa, KS, USA D Pipkorn Pfizer Inc Ann Arbor, MI, USA JC Price University of Georgia Athens, GA, USA MA Repka University of Mississippi University, MS, USA B Sarsfield Bristol-Myers Squibb New Brunswick, NJ, USA T Schmeller BASF Aktiengesellschaft Ludwigshafen, Germany A Schoch Palatinit GmbH Mannheim, Germany CJ Sciarra Sciarra Laboratories Inc Hicksville, NY, USA Contributors xi JJ Sciarra Sciarra Laboratories Inc Hicksville, NY, USA SA Shah Watson Pharmaceuticals Corona, CA, USA RM Shanker Pfizer Inc Groton, CT, USA PJ Sheskey The Dow Chemical Co Midland, MI, USA AJ Shukla University of Tennessee Memphis, TN, USA KK Singh SNDT Women’s University Mumbai, India R Steer AstraZeneca Loughborough, UK JT Stewart University of Georgia Athens, GA, USA Y Sun University of Tennessee Memphis, TN, USA AK Taylor Baton Rouge, LA, USA MS Tesconi Wyeth Research Pearl River, NY, USA D Thassu UCB Pharma Inc Rochester, NY, USA BF Truitt Pfizer Inc Groton, CT, USA CK Tye Pfizer Inc Kalamazoo, MI, USA HM Unvala Bayer Corporation Myerstown, PA, USA KD Vaughan Boots Healthcare International Nottingham, UK H Wang Pfizer Inc Groton, CT, USA PJ Weller Royal Pharmaceutical Society of Great Britain London, UK AJ Winfield Aberdeen, UK AW Wood GlaxoSmithKline Research Triangle Park, NC, USA M Yelvigi Wyeth Research Pearl River, NY, USA PM Young University of Sydney
