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DRUGS AND THE PHARMACEUTICAL SCIENCESVOLUME 199SECOND EDITIONPharmaceuticalPreformulation andFormulationA Practical Guide from Candidate Drug Selection to Commercial Dosage Formedited byMark Gibson

PharmaceuticalPreformulation andFormulation

DRUGS AND THE PHARMACEUTICAL SCIENCESA Series of Textbooks and MonographsExecutive EditorJames SwarbrickPharmaceuTech, Inc.Pinehurst, North CarolinaAdvisory BoardLarry L. AugsburgerUniversity of MarylandBaltimore, MarylandJennifer B. DressmanUniversity of Frankfurt Instituteof Pharmaceutical TechnologyFrankfurt, GermanyAnthony J. HickeyUniversity of North CarolinaSchool of PharmacyChapel Hill, North CarolinaAjaz HussainSandozPrinceton, New JerseyJoseph W. PolliGlaxoSmithKlineResearch Triangle ParkNorth CarolinaStephen G. SchulmanHarry G. BrittainCenter for Pharmaceutical Physics Milford,New JerseyRobert GurnyUniversite de GeneveGeneve, SwitzerlandJeffrey A. HughesUniversity of Florida Collegeof PharmacyGainesville, FloridaVincent H. L. LeeUS FDA Center for DrugEvaluation and ResearchLos Angeles, CaliforniaKinam ParkPurdue UniversityWest Lafayette, IndianaJerome P. SkellyAlexandria, VirginiaUniversity of FloridaGainesville, FloridaElizabeth M. ToppYuichi SugiyamaUniversity of KansasLawrence, KansasUniversity of Tokyo, Tokyo, JapanGeoffrey T. TuckerUniversity of SheffieldRoyal Hallamshire HospitalSheffield, United KingdomPeter YorkUniversity of BradfordSchool of PharmacyBradford, United Kingdom

For information on volumes 1–149 in the Drugs and PharmaceuticalScience Series, please visit www.informahealthcare.com150. Laboratory Auditing for Quality and Regulatory Compliance, Donald Singer,Raluca-Ioana Stefan, and Jacobus van Staden151. Active Pharmaceutical Ingredients: Development, Manufacturing, and Regulation,edited by Stanley Nusim152. Preclinical Drug Development, edited by Mark C. Rogge and David R. Taft153. Pharmaceutical Stress Testing: Predicting Drug Degradation, edited bySteven W. Baertschi154. Handbook of Pharmaceutical Granulation Technology: Second Edition,edited by Dilip M. Parikh155. Percutaneous Absorption: h Edition, edited by Robert L. Bronaugh and Howard I. Maibach156. Pharmacogenomics: Second Edition, edited by Werner Kalow, Urs A. Meyerand Rachel F. Tyndale157. Pharmaceutical Process Scale-Up, Second Edition, edited by Michael Levin158. Microencapsulation: Methods and Industrial Applications, Second Edition,edited by Simon Benita159. Nanoparticle Technology for Drug Delivery, edited by Ram B. Gupta andUday B. Kompella160. Spectroscopy of Pharmaceutical Solids, edited by Harry G. Brittain161. Dose Optimization in Drug Development, edited by Rajesh Krishna162. Herbal Supplements-Drug Interactions: Scientific and Regulatory Perspectives,edited by Y. W. Francis Lam, Shiew-Mei Huang, and Stephen D. Hall163. Pharmaceutical Photostability and Stabilization Technology, edited byJoseph T. Piechocki and Karl Thoma164. Environmental Monitoring for Cleanrooms and Controlled Environments,edited by Anne Marie Dixon165. Pharmaceutical Product Development: In Vitro-In Vivo Correlation, edited byDakshina Murthy Chilukuri, Gangadhar Sunkara, and David Young166. Nanoparticulate Drug Delivery Systems, edited by Deepak Thassu, MichelDeleers, and Yashwant Pathak167. Endotoxins: Pyrogens, LAL Testing and Depyrogenation, Third Edition,edited by Kevin L. Williams168. Good Laboratory Practice Regulations, Fourth Edition, edited by AnneSandy Weinberg169. Good Manufacturing Practices for Pharmaceuticals, Sixth Edition,edited by Joseph D. Nally170. Oral-Lipid Based Formulations: Enhancing the Bioavailability of PoorlyWater-soluble Drugs, edited by David J. Hauss171. Handbook of Bioequivalence Testing, edited by Sarfaraz K. Niazi172. Advanced Drug Formulation Design to Optimize Therapeutic Outcomes,edited by Robert O. Williams III, David R. Taft, and Jason T. McConville173. Clean-in-Place for Biopharmaceutical Processes, edited by DaleA. Seiberling174. Filtration and Purification in the Biopharmaceutical Industry, Second Edition,edited by Maik W. Jornitz and Theodore H. Meltzer175. Protein Formulation and Delivery, Second Edition, edited by EugeneJ. McNally and Jayne E. Hastedt

176. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, ThirdEdition, edited by James McGinity and Linda A. Felton177. Dermal Absorption and Toxicity Assessment, Second Edition, edited byMichael S. Roberts and Kenneth A. Walters178. Preformulation Solid Dosage Form Development, edited by Moji C. Adeyeyeand Harry G. Brittain179. Drug-Drug Interactions, Second Edition, edited by A. David Rodrigues180. Generic Drug Product Development: Bioequivalence Issues, edited byIsadore Kanfer and Leon Shargel181. Pharmaceutical Pre-Approval Inspections: A Guide to Regulatory Success,Second Edition, edited by Martin D. Hynes III182. Pharmaceutical Project Management, Second Edition, edited byAnthony Kennedy183. Modified Release Drug Delivery Technology, Second Edition, Volume 1,edited by Michael J. Rathbone, Jonathan Hadgraft, Michael S. Roberts,and Majella E. Lane184. Modified-Release Drug Delivery Technology, Second Edition, Volume 2,edited by Michael J. Rathbone, Jonathan Hadgraft, Michael S. Roberts, andMajella E. Lane185. The Pharmaceutical Regulatory Process, Second Edition, edited byIra R. Berry and Robert P. Martin186. Handbook of Drug Metabolism, Second Edition, edited by Paul G. Pearson andLarry C. Wienkers187. Preclinical Drug Development, Second Edition, edited by Mark Rogge andDavid R. Taft188. Modern Pharmaceutics, Fifth Edition, Volume 1: Basic Principles and Systems,edited by Alexander T. Florence and Juergen Siepmann189. Modern Pharmaceutics, Fifth Edition, Volume 2: Applications and Advances,edited by Alexander T. Florence and Juergen Siepmann190. New Drug Approval Process, Fifth Edition, edited by Richard A.Guarino191. Drug Delivery Nanoparticulate Formulation and Characterization, edited byYashwant Pathak and Deepak Thassu192. Polymorphism of Pharmaceutical Solids, Second Edition, edited by Harry G. Brittain193. Oral Drug Absorption: Prediction and Assessment, Second Edition, edited byJennifer J. Dressman, hans Lennernas, and Christos Reppas194. Biodrug Delivery Systems: Fundamentals, Applications, and Clinical Development,edited by Mariko Morista and Kinam Park195. Pharmaceutical Process Engineering, Second Edition, edited by Anthony J. Hickeyand David Ganderton196. Handbook of Drug Screening, Second Edition, edited by Ramakrishna Seethala andLitao Zhang197. Pharmaceutical Powder Compaction Technology, Second Edition, edited byMetin Celik198. Handbook of Pharmaceutical Granulation Technology, Dilip M. Parikh199. Pharmaceutical Preformulation and Formulation: A Practical Guide from CandidateDrug Selection to Commercial Dosage Form, Second Edition, edited byMark Gibson

PharmaceuticalPreformulation andFormulationSecond EditionA Practical Guide from Candidate Drug Selection to Commercial Dosage Formedited byMark GibsonAstraZeneca R&D CharnwoodLoughborough, Leicestershire, UK

Informa Healthcare USA, Inc.52 Vanderbilt AvenueNew York, NY 10017# 2009 by Informa Healthcare USA, Inc.Informa Healthcare is an Informa businessNo claim to original U.S. Government worksPrinted in the United States of America on acid-free paper10 9 8 7 6 5 4 3 2 1International Standard Book Number-10: 1-4200-7317-6 (Hardcover)International Standard Book Number-13: 978-1-4200-7317-1 (Hardcover)This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted withpermission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publishreliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materialsor for the consequence of their use.No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, orother means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any informationstorage or retrieval system, without written permission from the publishers.For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923,978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. Fororganizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only foridentification and explanation without intent to infringe.Library of Congress Cataloging-in-Publication DataPharmaceutical preformulation and formulation: A practical guide from candidate drugselection to commercial dosage form / edited by Mark Gibson.—2nd ed.p. ; cm. — (Drugs and the pharmaceutical sciences ; 199)Includes bibliographical references and index.ISBN-13: 978-1-4200-7317-1 (hb : alk. paper)ISBN-10: 1-4200-7317-6 (hb : alk. paper) 1. Drugs—Dosage forms.I. Gibson, Mark, 1957- II. Series: Drugs and the pharmaceuticalsciences ; v. 199.[DNLM: 1. Drug Compounding. 2. Biopharmaceutics—methods. 3.Dosage Forms. 4. Drug Discovery. 5. Drug Evaluation. W1 DR893B v.1992009 / QV 778 P53535 2009]RS200.P425 20096150 .1—dc222009012458For Corporate Sales and Reprint Permissions call 212-520-2700 or write to: Sales Department, 52 Vanderbilt Avenue,16th floor, New York, NY 10017.Visit the Informa Web site atwww.informa.comand the Informa Healthcare Web site atwww.informahealthcare.com