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Drug penetration enhancement: Theory and applications
310
Book Reviews/Journal
of Controlled Release 31 (I 994) 307-312
Allen E. Cato (Ed.), Clinical Drug Trials and Tribulations, Drugs and the Pharmaceutical Sciences Series, Volume 34, Marcel Dekker, NY, 1988,413 pp. This book reviews, via contributions from a number of authors, the often daunting task of seeing a new chemical entity from research through clinical trials to become a marketed new drug. The chapters, in the order presented, provide almost a workbook for those unfamiliar with the procedures involved both in clinical testing of potential drugs as well as the submission procedures for getting these drugs approved. Most of the weight of the information centers, as expected, on developing clinical trials, the laboratory tests needed during such trials, and strategies for analyzing the data from these trials. The book is useful, even if much of the procedural information has changed since its 1988 publication, as a starting point for designing and carrying out successful clinical trials. Within the factual information, the reader can find insights and helpful hints from researchers who have already been through numerous clinical trials and drug submissions. For those working in controlled release, this book can be interesting and informative as a reference for general design and analysis of clinical trials, but the information contained is targeted to new drug entities and not necessarily novel methods or devices for delivery. The timeliness of the book is also a concern as federal regulations and requirements are always evolving and changing,so that what was state of the art six years ago might no longer be sufficient. LISA BRANNON-PEPPAS Biogel Technology, Inc. Indianapolis, IN, USA
Dean S. Hsieh, Ed., Drug Penetration Enhancement: Theory and Applications, Marcel Dekker, NY, 1994, xi + 426 pp., $ 150. The back cover of this book claims that it provides ‘the first comprehensive review of drug penetration enhancement.’ One basis for this statement is that the text also includes contributions addressing enhancement of drug transport across epithelial membranes
other than the skin. This is a key distinction since the same publishing house released Pharmaceutical Skin Penetration Enhancement (eds. K.A. Walters and J. Hadgraft)in late 1993 (not, as the editor mistakenly references in Chapter 1, 1990). The latter book, in my opinion, could also be described as a ‘comprehensive review’, albeit focused specifically on the skin. So, to what extent does Dr. Hsieh’s book go beyond that of Walters and Hadgraft? The Table of Contents reveals a chapter on basic mechanisms of ‘transepithelium transport enhancement’, two chapters on enhancement of nasal delivery, and two addressing the ocular route. Apart from the introductory chapter, the remaining 13 contributions are all concerned with the skin. Unlike the use of ‘comprehensive’ in the publicity, to say that there is overlap with Walters/Hadgraft would not be an exaggeration! Furthermore, even a cursory reading of the Preface and introductory chapter does not fill the reader with confidence that an informed and authorative text is to follow. There are only seven FDA-approved transderma1 drugs, so misspelling one of them (fantanyl, sic) is inexcusable; describing Azone as a 7-membered ring lactim (?) is unnecessarily inaccurate; going on to say, without any reference that application of this enhancer for times as short as 1 minute can compromise skin integrity for as long as 2 weeks is unprofessional. Given that the author of this statement is the founder of a company based on competing enhancer technology, one is left wondering about issues of objectivity and appropriateness. In the Introduction, Dr. Hsieh poses a number of important questions for ‘the reader to ponder’, answers to which ‘may or may not be found within this volume’. I would have hoped that the Editor would have known if the answers were there and if not, why not. Some of these questions, in any case, are either trivial (What is permeation enhancement? What is a penetration ‘inhibitor’ as compared to a permeation ‘enhancer’?) or rhetorical (Can enhancers be used to achieve formulation objectives?). Nevertheless, in the chapters that follow, a number of authors have attempted to communicate some useful information and insight to the reader. Contributions on the delivery of peptides and proteins across mucosal permeability/metabolic barriers and toxicological evaluation after intranasal drug delivery stand out. Elsewhere, particularly in the transdermal area, much has been said before and much, in addition,
Book Reviews/Journal
of Controlled Release 31(1994) 307-312
is covered more critically and with greater insight in Walters and Hadgraft’s book and elsewhere. So, would I recommend this new addition to the ‘drug delivery library’? For the reasons stated above, with at best only below-average enthusiasm, I’m afraid. In scanning the references at the end of each chapter, I was struck by the following observations: (a) I found only one 1992 reference and just a handful or so of papers from 1991; (b) the referencing style was irritatingly nonuniform from chapter to chapter (e.g., with/without titles of articles); and (c) a distressing lack of attention to accuracy was apparent - see, for example, citation no. 33 on page 138: the first author’s initial is wrong (it should be M. not J.), co-authors names are missing (including my own, a particularly grave omission) and in the title, the Lineweaver of Lineweaver-Burk fame has been contracted to Linewar! Overall, then, I would have this on my shelf for completeness only; to be honest, in these days of shrinking library budgets, I would certainly think twice before recommending this text for institutional purchase.
RICHARD H. GUY University of California, San Francisco, CA, USA
R.Gurny and A.Teubner, Eds. Dermal and Transderma1 Drug Delivery, New Insights and Perspectives, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 1993, 193 pp., DM 59.20. This book is a compilation of the meeting notes from the 1991 meeting of the International Association for Pharmaceutical Technology held in Munich. The book contains informative articles on formulations, modelling/mechanistic aspects of percutaneous absorption, one article on electrically-enhanced delivery of macromolecules and another on the regulatory aspects of both topicals and transdermals. The first section, on the physicochemical and biological considerations for formulating topicals and designing ~ansderm~s, is well served by practitioners from industry and academia. Following an historical perspective on transdermals (G. Cleary) is a Iengthy
311
article on the limitations placed on the topical and transdermal formulator (G.L. Flynn andN.D. Weiner). This article contains particularly useful information on the complexities of topical drug delivery, highlighting the fact that the science is well behind the art of the formulator, while the situation is more sanguine for the case of transdermal drug delivery. A little out of place, but nevertheless interesting, is the article on the lipid structure of the skin barrier (Bouwstra et al.); the work describes the use of wide-angle X-ray scattering to follow the structure of the lipid bilayers of human and murine stratum corneum ( s.c.) after various methods of treatment. The article by Tiemessen addresses the possible use of si1iconels.c. sandwiches for in-vitro permeation measurements, while the work by Prof. Barry advocates the use of an Enhancement Index to grade potential chemical enhancers. Although I found this section to be the most interesting in the book, it was disappointing not to have an article on the materials currently being used for both transdermals and topicals. This would have rounded off the section nicely. The second ‘section’ (the divisions are rather arbitrary, and based loosely on the Editors’), deals with theoretical aspects of drug transport from a device into the bloodstream, as well as a useful comparison of the therapeutic value of some commercial transdermals. The articles on the modelling of drug transport (by Guy and Potts, and by Hadgraft and Wolff) are both well-written, and differ in the level of emphasis placed on where the drugs end up. In the case of the former, it is permeation through the s.c., while the latter takes the drug a few steps beyond into viable tissue. The article on electrically-enhanced delivery of macromolecules is a good compilation of data on delivery of peptides; the ph~macokinetic and pharmacodynamic analyses should prove to be particularly useful. Overall, I found the book to be a very timely and useful compilation of both theory and practice. Of all the books that deal with either topical or transdermal delivery, this volume is the most comprehensive. I found the easy-to-use paperback format refreshingly different, and the production appears good. However, I found some things that were annoying and unworthy of an otherwise excellent publication. The volume is littered with ty~graphical and proo~eading errors, particularly in Chapter II. Some articles could have benefited from editorial corrections, e.g., Chapter IX,
Book Reviews/Journal
of Controlled Release 31 (I 994) 307-312
Allen E. Cato (Ed.), Clinical Drug Trials and Tribulations, Drugs and the Pharmaceutical Sciences Series, Volume 34, Marcel Dekker, NY, 1988,413 pp. This book reviews, via contributions from a number of authors, the often daunting task of seeing a new chemical entity from research through clinical trials to become a marketed new drug. The chapters, in the order presented, provide almost a workbook for those unfamiliar with the procedures involved both in clinical testing of potential drugs as well as the submission procedures for getting these drugs approved. Most of the weight of the information centers, as expected, on developing clinical trials, the laboratory tests needed during such trials, and strategies for analyzing the data from these trials. The book is useful, even if much of the procedural information has changed since its 1988 publication, as a starting point for designing and carrying out successful clinical trials. Within the factual information, the reader can find insights and helpful hints from researchers who have already been through numerous clinical trials and drug submissions. For those working in controlled release, this book can be interesting and informative as a reference for general design and analysis of clinical trials, but the information contained is targeted to new drug entities and not necessarily novel methods or devices for delivery. The timeliness of the book is also a concern as federal regulations and requirements are always evolving and changing,so that what was state of the art six years ago might no longer be sufficient. LISA BRANNON-PEPPAS Biogel Technology, Inc. Indianapolis, IN, USA
Dean S. Hsieh, Ed., Drug Penetration Enhancement: Theory and Applications, Marcel Dekker, NY, 1994, xi + 426 pp., $ 150. The back cover of this book claims that it provides ‘the first comprehensive review of drug penetration enhancement.’ One basis for this statement is that the text also includes contributions addressing enhancement of drug transport across epithelial membranes
other than the skin. This is a key distinction since the same publishing house released Pharmaceutical Skin Penetration Enhancement (eds. K.A. Walters and J. Hadgraft)in late 1993 (not, as the editor mistakenly references in Chapter 1, 1990). The latter book, in my opinion, could also be described as a ‘comprehensive review’, albeit focused specifically on the skin. So, to what extent does Dr. Hsieh’s book go beyond that of Walters and Hadgraft? The Table of Contents reveals a chapter on basic mechanisms of ‘transepithelium transport enhancement’, two chapters on enhancement of nasal delivery, and two addressing the ocular route. Apart from the introductory chapter, the remaining 13 contributions are all concerned with the skin. Unlike the use of ‘comprehensive’ in the publicity, to say that there is overlap with Walters/Hadgraft would not be an exaggeration! Furthermore, even a cursory reading of the Preface and introductory chapter does not fill the reader with confidence that an informed and authorative text is to follow. There are only seven FDA-approved transderma1 drugs, so misspelling one of them (fantanyl, sic) is inexcusable; describing Azone as a 7-membered ring lactim (?) is unnecessarily inaccurate; going on to say, without any reference that application of this enhancer for times as short as 1 minute can compromise skin integrity for as long as 2 weeks is unprofessional. Given that the author of this statement is the founder of a company based on competing enhancer technology, one is left wondering about issues of objectivity and appropriateness. In the Introduction, Dr. Hsieh poses a number of important questions for ‘the reader to ponder’, answers to which ‘may or may not be found within this volume’. I would have hoped that the Editor would have known if the answers were there and if not, why not. Some of these questions, in any case, are either trivial (What is permeation enhancement? What is a penetration ‘inhibitor’ as compared to a permeation ‘enhancer’?) or rhetorical (Can enhancers be used to achieve formulation objectives?). Nevertheless, in the chapters that follow, a number of authors have attempted to communicate some useful information and insight to the reader. Contributions on the delivery of peptides and proteins across mucosal permeability/metabolic barriers and toxicological evaluation after intranasal drug delivery stand out. Elsewhere, particularly in the transdermal area, much has been said before and much, in addition,
Book Reviews/Journal
of Controlled Release 31(1994) 307-312
is covered more critically and with greater insight in Walters and Hadgraft’s book and elsewhere. So, would I recommend this new addition to the ‘drug delivery library’? For the reasons stated above, with at best only below-average enthusiasm, I’m afraid. In scanning the references at the end of each chapter, I was struck by the following observations: (a) I found only one 1992 reference and just a handful or so of papers from 1991; (b) the referencing style was irritatingly nonuniform from chapter to chapter (e.g., with/without titles of articles); and (c) a distressing lack of attention to accuracy was apparent - see, for example, citation no. 33 on page 138: the first author’s initial is wrong (it should be M. not J.), co-authors names are missing (including my own, a particularly grave omission) and in the title, the Lineweaver of Lineweaver-Burk fame has been contracted to Linewar! Overall, then, I would have this on my shelf for completeness only; to be honest, in these days of shrinking library budgets, I would certainly think twice before recommending this text for institutional purchase.
RICHARD H. GUY University of California, San Francisco, CA, USA
R.Gurny and A.Teubner, Eds. Dermal and Transderma1 Drug Delivery, New Insights and Perspectives, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 1993, 193 pp., DM 59.20. This book is a compilation of the meeting notes from the 1991 meeting of the International Association for Pharmaceutical Technology held in Munich. The book contains informative articles on formulations, modelling/mechanistic aspects of percutaneous absorption, one article on electrically-enhanced delivery of macromolecules and another on the regulatory aspects of both topicals and transdermals. The first section, on the physicochemical and biological considerations for formulating topicals and designing ~ansderm~s, is well served by practitioners from industry and academia. Following an historical perspective on transdermals (G. Cleary) is a Iengthy
311
article on the limitations placed on the topical and transdermal formulator (G.L. Flynn andN.D. Weiner). This article contains particularly useful information on the complexities of topical drug delivery, highlighting the fact that the science is well behind the art of the formulator, while the situation is more sanguine for the case of transdermal drug delivery. A little out of place, but nevertheless interesting, is the article on the lipid structure of the skin barrier (Bouwstra et al.); the work describes the use of wide-angle X-ray scattering to follow the structure of the lipid bilayers of human and murine stratum corneum ( s.c.) after various methods of treatment. The article by Tiemessen addresses the possible use of si1iconels.c. sandwiches for in-vitro permeation measurements, while the work by Prof. Barry advocates the use of an Enhancement Index to grade potential chemical enhancers. Although I found this section to be the most interesting in the book, it was disappointing not to have an article on the materials currently being used for both transdermals and topicals. This would have rounded off the section nicely. The second ‘section’ (the divisions are rather arbitrary, and based loosely on the Editors’), deals with theoretical aspects of drug transport from a device into the bloodstream, as well as a useful comparison of the therapeutic value of some commercial transdermals. The articles on the modelling of drug transport (by Guy and Potts, and by Hadgraft and Wolff) are both well-written, and differ in the level of emphasis placed on where the drugs end up. In the case of the former, it is permeation through the s.c., while the latter takes the drug a few steps beyond into viable tissue. The article on electrically-enhanced delivery of macromolecules is a good compilation of data on delivery of peptides; the ph~macokinetic and pharmacodynamic analyses should prove to be particularly useful. Overall, I found the book to be a very timely and useful compilation of both theory and practice. Of all the books that deal with either topical or transdermal delivery, this volume is the most comprehensive. I found the easy-to-use paperback format refreshingly different, and the production appears good. However, I found some things that were annoying and unworthy of an otherwise excellent publication. The volume is littered with ty~graphical and proo~eading errors, particularly in Chapter II. Some articles could have benefited from editorial corrections, e.g., Chapter IX,