DRUGS AND THE PHARMACEUTICAL SCIENCES VOLUME 199 SECOND EDITION Pharmaceutical Preformulation and Formulation A Practical Guide from Candidate Drug Selection to Commercial Dosage Form edited by Mark Gibson Pharmaceutical Preformulation and Formulation DRUGS AND THE PHARMACEUTICAL SCIENCES A Series of Textbooks and Monographs Executive Editor James Swarbrick PharmaceuTech, Inc. Pinehurst, North Carolina Advisory Board Larry L. Brittain University of Maryland Center for Pharmaceutical Physics Milford, Baltimore, Maryland New Jersey Jennifer B. Dressman Robert Gurny University of Frankfurt Institute Universite de Geneve of Pharmaceutical Technology Geneve, Switzerland Frankfurt, Germany Jeffrey A.
Hickey University of Florida College University of North Carolina of Pharmacy School of Pharmacy Gainesville, Florida Chapel Hill, North Carolina Vincent H. Lee Ajaz Hussain US FDA Center for Drug Sandoz Evaluation and Research Princeton, New Jersey Los Angeles, California Joseph W. Polli Kinam Park GlaxoSmithKline Purdue University Research Triangle Park West Lafayette, Indiana North Carolina Jerome P. Schulman Alexandria, Virginia University of Florida Gainesville, Florida Elizabeth M.
Topp University of Kansas Yuichi Sugiyama Lawrence, Kansas University of Tokyo, Tokyo, Japan Peter York Geoffrey T. Tucker University of Bradford University of Sheffield School of Pharmacy Royal Hallamshire Hospital Bradford, United Kingdom Sheffield, United Kingdom For information on volumes 1–149 in the Drugs and Pharmaceutical Science Series, please visit www. Laboratory Auditing for Quality and Regulatory Compliance, Donald Singer, Raluca-Ioana Stefan, and Jacobus van Staden 151. Active Pharmaceutical Ingredients: Development, Manufacturing, and Regulation, edited by Stanley Nusim 152.
Preclinical Drug Development, edited by Mark C. Rogge and David R. Pharmaceutical Stress Testing: Predicting Drug Degradation, edited by Steven W. Handbook of Pharmaceutical Granulation Technology: Second Edition, edited by Dilip M.
Percutaneous Absorption: Drugs–Cosmetics–Mechanisms–Methodology, Fourth Edition, edited by Robert L. Bronaugh and Howard I. Pharmacogenomics: Second Edition, edited by Werner Kalow, Urs A. Meyer and Rachel F.
Pharmaceutical Process Scale-Up, Second Edition, edited by Michael Levin 158. Microencapsulation: Methods and Industrial Applications, Second Edition, edited by Simon Benita 159. Nanoparticle Technology for Drug Delivery, edited by Ram B. Gupta and Uday B.
Spectroscopy of Pharmaceutical Solids, edited by Harry G. Dose Optimization in Drug Development, edited by Rajesh Krishna 162. Herbal Supplements-Drug Interactions: Scientific and Regulatory Perspectives, edited by Y. Francis Lam, Shiew-Mei Huang, and Stephen D.
Pharmaceutical Photostability and Stabilization Technology, edited by Joseph T. Piechocki and Karl Thoma 164. Environmental Monitoring for Cleanrooms and Controlled Environments, edited by Anne Marie Dixon 165. Pharmaceutical Product Development: In Vitro-In Vivo Correlation, edited by Dakshina Murthy Chilukuri, Gangadhar Sunkara, and David Young 166.
Nanoparticulate Drug Delivery Systems, edited by Deepak Thassu, Michel Deleers, and Yashwant Pathak 167. Endotoxins: Pyrogens, LAL Testing and Depyrogenation, Third Edition, edited by Kevin L. Good Laboratory Practice Regulations, Fourth Edition, edited by Anne Sandy Weinberg 169. Good Manufacturing Practices for Pharmaceuticals, Sixth Edition, edited by Joseph D.
Oral-Lipid Based Formulations: Enhancing the Bioavailability of Poorly Water-soluble Drugs, edited by David J. Handbook of Bioequivalence Testing, edited by Sarfaraz K. Advanced Drug Formulation Design to Optimize Therapeutic Outcomes, edited by Robert O. Williams III, David R.
Taft, and Jason T. Clean-in-Place for Biopharmaceutical Processes, edited by Dale A. Filtration and Purification in the Biopharmaceutical Industry, Second Edition, edited by Maik W. Jornitz and Theodore H.
Protein Formulation and Delivery, Second Edition, edited by Eugene J. McNally and Jayne E. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, Third Edition, edited by James McGinity and Linda A. Dermal Absorption and Toxicity Assessment, Second Edition, edited by Michael S.
Roberts and Kenneth A. Preformulation Solid Dosage Form Development, edited by Moji C. Adeyeye and Harry G. Drug-Drug Interactions, Second Edition, edited by A.
Generic Drug Product Development: Bioequivalence Issues, edited by Isadore Kanfer and Leon Shargel 181. Pharmaceutical Pre-Approval Inspections: A Guide to Regulatory Success, Second Edition, edited by Martin D. Pharmaceutical Project Management, Second Edition, edited by Anthony Kennedy 183. Modified Release Drug Delivery Technology, Second Edition, Volume 1, edited by Michael J.
Rathbone, Jonathan Hadgraft, Michael S. Roberts, and Majella E. Modified-Release Drug Delivery Technology, Second Edition, Volume 2, edited by Michael J. Rathbone, Jonathan Hadgraft, Michael S.
Roberts, and Majella E. The Pharmaceutical Regulatory Process, Second Edition, edited by Ira R. Berry and Robert P. Handbook of Drug Metabolism, Second Edition, edited by Paul G.
Pearson and Larry C. Preclinical Drug Development, Second Edition, edited by Mark Rogge and David R. Modern Pharmaceutics, Fifth Edition, Volume 1: Basic Principles and Systems, edited by Alexander T. Florence and Juergen Siepmann 189.
Modern Pharmaceutics, Fifth Edition, Volume 2: Applications and Advances, edited by Alexander T. Florence and Juergen Siepmann 190. New Drug Approval Process, Fifth Edition, edited by Richard A. Drug Delivery Nanoparticulate Formulation and Characterization, edited by Yashwant Pathak and Deepak Thassu 192.
Polymorphism of Pharmaceutical Solids, Second Edition, edited by Harry G. Oral Drug Absorption: Prediction and Assessment, Second Edition, edited by Jennifer J. Dressman, hans Lennernas, and Christos Reppas 194. Biodrug Delivery Systems: Fundamentals, Applications, and Clinical Development, edited by Mariko Morista and Kinam Park 195.
Pharmaceutical Process Engineering, Second Edition, edited by Anthony J. Hickey and David Ganderton 196. Handbook of Drug Screening, Second Edition, edited by Ramakrishna Seethala and Litao Zhang 197. Pharmaceutical Powder Compaction Technology, Second Edition, edited by Metin Celik 198.
Handbook of Pharmaceutical Granulation Technology, Dilip M. Pharmaceutical Preformulation and Formulation: A Practical Guide from Candidate Drug Selection to Commercial Dosage Form, Second Edition, edited by Mark Gibson Pharmaceutical Preformulation and Formulation Second Edition A Practical Guide from Candidate Drug Selection to Commercial Dosage Form edited by Mark Gibson AstraZeneca R&D Charnwood Loughborough, Leicestershire, UK Informa Healthcare USA, Inc. 52 Vanderbilt Avenue New York, NY 10017 # 2009 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business No claim to original U.
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ISBN-13: 978-1-4200-7317-1 (hb : alk. paper) ISBN-10: 1-4200-7317-6 (hb : alk. Drugs—Dosage forms. Gibson, Mark, 1957- II.
Series: Drugs and the pharmaceutical sciences ; v.1—dc22 2009012458 For 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 at www.com and the Informa Healthcare Web site at www.com Preface The first edition of this book published in 2001 has been more successful than I ever imagined, as indicated by the excellent reviews it has received, the continued demand, and impressive sales! I believe that the main reasons for its popularity are that there was a significant gap in the literature and also that the information presented was based on the extensive experiences of the various contributors who were all actively working in the industry and were willing to share “best practice” from their knowledge and experiences. The book is intended to be a practical guide to pharmaceutical preformulation and formulation to be used as a reference source or a guidance tool to those working in the pharmaceutical industry or related industries, such as biopharmaceuticals or medical devices, or anyone wanting an insight into the subject area. Indeed, this book has also proved to be a valuable text for undergraduate and postgraduate courses in industrial pharmacy and pharmaceutical technology.
A second edition is required because preformulation and formulation technology continues to develop and also because there are bound to be some gaps and improvements to be filled. The second edition still meets the main objectives of the first edition, that is, to l provide a logical and structured approach to product development, with key stages identified and the preformulation, biopharmaceutics, and formulation activities and typical issues at each stage discussed, wherever possible with real or worked examples, l emphasize what practical studies need to be undertaken for what reasons and during what key stages of the drug development process, and l provide separate chapters on the formulation development of each route and type of dosage forms. The pressure to accelerate the drug development process, shorten the development timelines, and launch new pharmaceutical products is even more intense than before, with fewer registrations year on year. Having a structured approach and doing the right things first time are essential elements for achieving this.
The chapters on product design and product optimization are still very relevant but have been updated to include the quality by design (QbD) and International Conference on Harmonisation (ICH) Q8 (product development), ICH Q9 (quality risk management), process analytical technology (PAT), and lean manufacturing principles that aim to link regulatory expectations to good science. Another significant change since the first edition is the growth of biopharmaceuticals, compared with small molecules, that deserves more attention. Pharmaceutical companies are shifting from developing small molecules to developing biopharmaceuticals to treat a wide range of diseases, and today approximately one in four drugs introduced to the market is a biopharmaceutical. Since the majority of biopharmaceuticals will be delivered by injection or infusion, the chapter on parenteral dosage forms has been updated to reflect this.
Focus has been given to the steps after purification, formulation, and subsequent fill-finish. Consider- ation has also been given in the other chapters for handling and developing biopharmaceutical dosage forms where there is some potential for drug delivery, for example, intranasal dosage forms. Elsewhere in the second edition, there are updates throughout the book to reflect on some omissions and developments since the first edition and make it up-to-date; for example, to reflect emerging “cutting-edge” technologies such as polymorph and salt selection and viii Preface prediction, molecular modeling and automation in preformulation studies, and more consider- ation for packaging technology during development of the various dosage forms. Once again I am indebted to all the contributors for giving up their time and energy in producing this updated version.
I am also indebted to my wife, Alison, and my family for their support and understanding during the time I have been busy working on this book. Mark Gibson Contents Preface vii Contributors xi 1. Introduction and Perspective 1 Mark Gibson 2. Aiding Candidate Drug Selection: Introduction and Objectives 11 Mark Gibson 3.
Preformulation Investigations using Small Amounts of Compound as an Aid to Candidate Drug Selection and Early Development 17 Gerry Steele and Talbir Austin 4. Biopharmaceutical Support in Candidate Drug Selection 129 Anna-Lena Ungell and Bertil Abrahamsson 5. Early Drug Development: Product Design 172 Mark Gibson 6. Preformulation as an Aid to Product Design in Early Drug Development 188 Gerry Steele 7.
Biopharmaceutical Support in Formulation Development 247 Bertil Abrahamsson and Anna-Lena Ungell 8. Product Optimization 289 Mark Gibson 9. Parenteral Dosage Forms 325 Joanne Broadhead and Mark Gibson 10.