DRUG DELIVERY SYSTEMS Second Edition Vasant V.Ranade Mannfred A.Hollinger CRC CRC PRESS PHARMACOLOGY TOXICOLOGY SERIES Also available as a printed book see title verso for ISBN details
Preface to the First Edition The introduction of the first successful drug delivery system brought about tremendous inte est in the us into the marketplace and many are now in different stages of product devel opment.Lately,a plethora of drug delivery departments and companies have emerged partly as a result of surging interest in generic drug development and continued technological advances are occurring in this area of pharma- ce utical research. The main goal of this book has been to collect current information in one volume to further research in drug delivery and to serve as an introduc- tion to the various systems.The aim has also been simply to identify areas of potential and real improvement in the drug treatment of disease as well as to review the different approaches and methods of assessment of novel drug deliv This be contains introductory and state-of-the-art information on lipo somes,monoclonal antibodies,use of polymers,implants,oral,transdermal, miscellaneous,intranasal,and ocular forms of drug delivery.Finally,a liter- ature review on the regulatory and global aspects of drug delivery systems nted.Obviously,in this rapidly expanding field,several in must ha nown by carly 1994,wheh most of the literature was collecter e occu ed d spite 0 orts to include ific advances k We hope this effort will prove to be of value to scientists,clinicians,and product development personnel seeking information in this area and this compilation of the introductory data should serve as a useful resource tool. Theednd oeptsdbed in this book are not ouwn do we make any claims indicating such a notio n nor do we se any credit.We are indebted to scientists and authors for their permission to use or include their research work.Particularly,we express our appreciation to the following:Drs.G.Gregoriadis,U.Persson,F.H.Roerdink,R.L.Juliano and D.Mufson for liposomes,Drs.E.Tomlinson,I.Schlom,W.Lebherz,G.F. Rowland and T.Suzuta for monoclonal antibodies,Drs.F.G.Hutchinson and I.B.Ll oyd for use of polymers Drs.F.The uwes and M.Sefton for implant Drs.D.Ganderton and S.S.Davis for oral drug delivery,Dr.B.W.Barry for transdermal drug delivery,Drs.Y.W.Chien,K.S.E.Su and D.Proctor for intranasal and ocular drug delivery,Capsugel Americas and SoloHill Engi-
Preface to the First Edition The introduction of the first successful drug delivery system brought about tremendous interest in the usage of delivery systems for entry of drugs into the systemic circulation of the body. Several drug delivery products followed into the marketplace and many are now in different stages of product development. Lately, a plethora of drug delivery departments and companies have emerged partly as a result of surging interest in generic drug development and continued technological advances are occurring in this area of pharmaceutical research. The main goal of this book has been to collect current information in one volume to further research in drug delivery and to serve as an introduction to the various systems. The aim has also been simply to identify areas of potential and real improvement in the drug treatment of disease as well as to review the different approaches and methods of assessment of novel drug delivery. This book contains introductory and state-of-the-art information on liposomes, monoclonal antibodies, use of polymers, implants, oral, transdermal, miscellaneous, intranasal, and ocular forms of drug delivery. Finally, a literature review on the regulatory and global aspects of drug delivery systems is presented. Obviously, in this rapidly expanding field, several important omissions must have occurred despite our efforts to include significant advances known by early 1994, when most of the literature was collected. We hope this effort will prove to be of value to scientists, clinicians, and product development personnel seeking information in this area and this compilation of the introductory data should serve as a useful resource tool. The research ideas and concepts described in this book are not our own and neither do we make any claims indicating such a notion nor do we seek any credit. We are indebted to scientists and authors for their permission to use or include their research work. Particularly, we express our appreciation to the following: Drs. G. Gregoriadis, U. Persson, F.H. Roerdink, R.L. Juliano and D. Mufson for liposomes, Drs. E. Tomlinson, J. Schlom, W. Lebherz, G.F. Rowland and T. Suzuta for monoclonal antibodies, Drs. F.G. Hutchinson and J.B. Lloyd for use of polymers, Drs. F. Theeuwes and M. Sefton for implants, Drs. D. Ganderton and S.S. Davis for oral drug delivery, Dr. B.W. Barry for transdermal drug delivery, Drs. Y.W. Chien, K.S.E. Su and D. Proctor for intranasal and ocular drug delivery, Capsugel Americas and SoloHill Engi-
Preface Inclusion of the material on drug delivery systems is organized based mainly on the uniqueness,originality,and potential application of the basic research toward commmercialization and ultimate product introduction into the mar- ket.Ev ery r searched ex 22a although it merits inclusion- voluminous book on each subject.This is beyond the intention or scope of this book,which is meant to serve simply as an introduction of a particular area to a researcher who is not an expert but would like to "get to know" ofrea of interest.The reader is requested to understand the background of th he or she attempts to form an opinion on the subject matter presented. In this second edition,every attempt is made to include material pub- lished between 1995 and 2002.The content has been expanded to provide integrated coverage of the topics in the first edition and to introduce the reader to new topics of general scientific interest. The authors thank all their associates for their continued support during the preparation of this book
Preface Inclusion of the material on drug delivery systems is organized based mainly on the uniqueness, originality, and potential application of the basic research toward commmercialization and ultimate product introduction into the market. Every researched example in a particular delivery system is not included — although it merits inclusion — because such an effort would result in a voluminous book on each subject. This is beyond the intention or scope of this book, which is meant to serve simply as an introduction of a particular area to a researcher who is not an expert but would like to “get to know” an area of interest. The reader is requested to understand the background of the production of this book before he or she attempts to form an opinion on the subject matter presented. In this second edition, every attempt is made to include material published between 1995 and 2002. The content has been expanded to provide integrated coverage of the topics in the first edition and to introduce the reader to new topics of general scientific interest. The authors thank all their associates for their continued support during the preparation of this book
Authors Vinayak (Vasant)V.Ranade,Ph.D.,is director of chemical sciences for Academic pharr aceuticals.Inc.in Lake Bluff,Illinois.He also holds a faculty Dr.Ranade earned his Ph.D.degree in organic chemistry from the Uni- versity of Bombay in 1965 and received his postdoctoral training in the College of Pharmacy at the University of Michigan,Ann Arbor.He has arch chemist for Abbott Laboratories,Mallinckrodt Inc.and ritica Care. Dr.Ranade is a member of the American Chemical Society,APhA Academy of Pharmaceutical Sciences and the honorary society,Sigma Xi. He was awarded the Council of Scientific and Industrial Research Fellow- ship,and was elected fellow of the American Institute of Chemists.He was ent of the Genia Czerniak Prize for Nuclear Medicine and Radiopharma 08y Dr.Ranade has been a reviewer for a number of scientific jounals,and his biography is listed in Who's Who and American Men and Women of Science and Technology.He has presented research work at the American Chemical Society,the APhA Academy of Pharmaceutical Sciences,and the American e of Cardiolo gy and Pha gy meetings eha than papers including original and abstracts.He is the recipient of several U.S.patents,and his research work has also been included in Canadian and European patents.He co-authored the first edition of this book titled Drug Delivery Systems published by CRC Press in 1995. Dr.Ranade's significant contributions to pharmaceutical research and development include synthesis of tumor imaging agents,formulations of cardiovascular and diuretic drugs,and chiral chromatographic separations of a variety of drugs.Dr.Ranade is also a consultant in the areas of chemical and pharamaceutical technology for some industrial organizations,securities market analysis companies,and research institutes in the U.S. Mannfred A.Hollinger,Ph.D.,is currently a professor emeritus in the Department of Medical Pharmacology and Toxicology,School of Medicine, University of California,Davis.Dr.Hollinger is the former editor of Current
Authors Vinayak (Vasant) V. Ranade, Ph.D., is director of chemical sciences for Academic Pharmaceuticals, Inc. in Lake Bluff, Illinois. He also holds a faculty position in the Department of Pharmacology at Rush-Presbyterian-St. Luke’s Medical Center in Chicago. Dr. Ranade earned his Ph.D. degree in organic chemistry from the University of Bombay in 1965 and received his postdoctoral training in the College of Pharmacy at the University of Michigan, Ann Arbor. He has worked as a research chemist for Abbott Laboratories, Mallinckrodt Inc., and DuPont Critical Care. Dr. Ranade is a member of the American Chemical Society, APhA Academy of Pharmaceutical Sciences and the honorary society, Sigma Xi. He was awarded the Council of Scientific and Industrial Research Fellowship, and was elected fellow of the American Institute of Chemists. He was the co-recipient of the Genia Czerniak Prize for Nuclear Medicine and Radiopharmacology. Dr. Ranade has been a reviewer for a number of scientific jounals, and his biography is listed in Who’s Who and American Men and Women of Science and Technology. He has presented research work at the American Chemical Society, the APhA Academy of Pharmaceutical Sciences, and the American College of Cardiology and Pharmacology meetings. He has published more than 90 papers including original and review articles, book chapters, and abstracts. He is the recipient of several U.S. patents, and his research work has also been included in Canadian and European patents. He co-authored the first edition of this book titled Drug Delivery Systems published by CRC Press in 1995. Dr. Ranade’s significant contributions to pharmaceutical research and development include synthesis of tumor imaging agents, formulations of cardiovascular and diuretic drugs, and chiral chromatographic separations of a variety of drugs. Dr. Ranade is also a consultant in the areas of chemical and pharamaceutical technology for some industrial organizations, securities market analysis companies, and research institutes in the U.S. Mannfred A. Hollinger, Ph.D., is currently a professor emeritus in the Department of Medical Pharmacology and Toxicology, School of Medicine, University of California, Davis. Dr. Hollinger is the former editor of Current
Contents Section one:Site-specific drug delivery Chapter one Site-specific drug delivery using liposomes as carriers. 3 Chapter two Site-specific drug delivery utilizing monoclonal antibodies. 35 Section two:Polymers,implantable drug delivery Chapter three Role of polymers in drug delivery .63 Chapter four Implants in drug delivery. .115 Section three:Oral drug delivery Chapter five Oral drug delivery. 149 Section four:Transdermal,intranasal,ocular,and miscellaneous drug delivery Chapter six Transdermal drug delivery. .207 Chapter seven Intranasal and ocular drug delivery. 249 Chapter eight Miscellaneous forms of drug delivery. 289
Contents Section one: Site-specific drug delivery Chapter one Site-specific drug delivery using liposomes as carriers.3 Chapter two Site-specific drug delivery utilizing monoclonal antibodies .35 Section two: Polymers, implantable drug delivery Chapter three Role of polymers in drug delivery .63 Chapter four Implants in drug delivery. 115 Section three: Oral drug delivery Chapter five Oral drug delivery .149 Section four: Transdermal, intranasal, ocular, and miscellaneous drug delivery Chapter six Transdermal drug delivery .207 Chapter seven Intranasal and ocular drug delivery .249 Chapter eight Miscellaneous forms of drug delivery .289