Controlled Drug Delivery: Fundamentals and Applications

731 Pages·1987·10.33 MB·English

by  Joseph R. Robinson and Vincent H. L. Lee

Controlled Drug Delivery
DRUGS AND THE PHARMACEUTICAL SCIENCES
A Series of Textbooks and Monographs
Edited by
James Swarbrick
School of Pharmacy
University of North Cam Una
Chape/ Hill, North Carolina
Volume 1. PHARMACOKINETICS, Milo Gibaldi and Donald Perrier
(out of print)
Volume 2. GOOD MANUFACTURING PRACTICES FOR
PHARMACEUTICALS: A PLAN FOR TOTAL QUALITY
CONTROL, Sidney H. Willig, Murray M. Tucker man, and
William S. Hitchings IV (out of print)
Volume 3. MICROENCAPSULATION, edited by J R. Nixon
Volume 4. DRUG METABOLISM: CHEMICAL AND BIOCHEMICAL
ASPECTS, Bernard Testa and Peter Jenner
Volume 5. NEW DRUGS: DISCOVERY AND DEVELOPMENT,
edited by Alan A. Rubin
Volume 6. SUSTAINED AND CONTROLLED RELEASE DRUG DELIVERY
SYSTEMS, edited by Joseph R. Robinson
Volume 7. MODERN PHARMACEUTICS, edited by Gilbert S.
Banker and Christopher T Rhodes
Volume 8. PRESCRIPTION DRUGS IN SHORT SUPPLY: CASE
HISTO RIES, Michael A. Sch wartz
Volume 9. ACTIVATED CHARCOAL: ANTIDOTAL AND OTHER
MEDICAL USES, David O. Cooney
Volume 10. CONCEPTS IN DRUG METABOLISM (in two parts), edited
by Peter Jenner and Bernard Testa
Volume 11. PHARMACEUTICAL ANALYSIS: MODERN METHODS
(in two parts), edited by James i/V. Munson
Volume 12. TECHNIQUES OF SOLUBILIZATION OF DRUGS,
edited by Samuel H. Yalkowsky
Volume 13. ORPHAN DRUGS .edited by Fred E. Karch
Volume 14. NOVEL DRUG DELIVERY SYSTEMS: FUNDAMENTALS,
DEVELOPMENTAL CONCEPTS, BIOMEDICAL ASSESSMENTS,
edited by Yie W. Chien
Volume 15. PHARMACOKINETICS, Second Edition, Revised and Expanded,
Milo Gibaldi and Donald Perrier
Volume 16. GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALS:
A PLAN FOR TOTAL QUALITY CONTROL, Second Edition,
Revised and Expanded, Sidney H. Willig, Murray M. Tuckerman,
and William S. Hitchings IV
Volume 17. FORMULATION OF VETERINARY DOSAGE FORMS, edited by
Jack Blodinger
Volume 18. DERMATOLOGICAL FORMULATIONS: PERCUTANEOUS
ABSORPTION, Brian W. Barry
Volume 19. THE CLINICAL RESEARCH PROCESS IN THE PHARMACEUTICAL
INDUSTRY, edited by Gary M. Matoren
Volume 20. MICROENCAPSULATION AND RELATED DRUG
PROCESSES, Patrick B. Deasy
Volume 21. DRUGS AND NUTRIENTS: THE INTERACTIVE
EFFECTS, edited by Daphne A. Roe and T. Colin
Campbell
Volume 22. BIOTECHNOLOGY OF INDUSTRIAL ANTIBIOTICS,
Erick J. Vandamme
Volume 23. PHARMACEUTICAL PROCESS VALIDATION,
edited by Bernard T. Loft us and Robert A. Nash
Volume.24. ANTICANCER AND INTERFERON AGENTS:
SYNTHESIS AND PROPERTIES, edited by Raphael
M. Ottenbrite and George B. Butler
Volume 25. PHARMACEUTICAL STATISTICS: PRACTICAL AND
CLINICAL APPLICATIONS, Sanford Bolton
Volume 26. DRUG DYNAMICS FOR ANALYTICAL, CLINICAL, AND BIOLOGICAL
CHEMISTS, Benjamin J. Gudzinowicz, Burrows T. Younkin, Jr., and Michael
J. Gudzinowicz
Volume 27. MODERN ANALYSIS OF ANTIBIOTICS, edited by Adorjan Aszalos
Volume 28. SOLUBILITY AND RELATED PROPERTIES, Kenneth C. James
Volume 29. CONTROLLED DRUG DELIVERY: FUNDAMENTALS AND
APPLICATIONS, Second Edition, Revised and Expanded,
Joseph R. Robinson and Vincent H. L. Lee
Other Volumes in Preparation
Controlled Drug Delivery
Fundamentals and Applications
SECOND EDITION,
REVISED AND EXPANDED
Edited by
Joseph R. Robinson Vincent H. L. Lee
SCHOOL OF PHARMACY SCHOOL OF PHARMACY
UNIVERSITY OF WISCONSIN UNIVERSITY OF SOUTHERN CALIFORNIA
MADISON, WISCONSIN LOS ANGELES, CALIFORNIA
MARCEL
MARCEL DEKKER, INC. NEW YORK • BASEL
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 1987 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Version Date: 20130305
International Standard Book Number-13: 978-1-4398-0516-9 (eBook - PDF)
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In memory of our fathers,
and to our mothers
Preface to the Second Edition
Controlled drug delivery is the phasing of drug administration to
the needs of a condition at hand so that an optimal amount of drug
is used to cure or control the condition in a minimum time. Research
in controlled drug delivery during the past decade has led to increas
ingly sophisticated means to sustain drug delivery. It has also stim
ulated greater awareness among the pharmaceutical industry, the
regulatory agencies, the health care profession, and the public at
large of the therapeutic advantages of controlled drug delivery sys
tems. Presently, the majority of these systems are based on syn
thetic polymers of some sort that differ in the degree of erodibility,
swellability, and sensitivity to the biological environment in which
they are placed. These polymers have been used to fabricate sys
tems such as microcapsules and nanoparticles for implantation, hy-
drogels for oral and parenteral drug delivery, the osmotic pump for
oral drug delivery, and patches for transdermal drug delivery.
Clearly, in order to fully utilize the potential of polymers in the
broad area of drug delivery, it is necessary to understand their
fundamental physical, chemical, and biological properties.
When the first edition of this text was written a decade ago,
liposomes were considered by many to be the answer to drug delivery
optimization in virtually all routes of drug administration. Research
since then has revealed that liposomes in particular and microparticu-
late carriers in general would probably have their greatest impact in
iv
Preface to the Second Edition I v
targeting drugs for diseases affecting the reticuloendothelial system,
to which these carriers are directed, as well as for diseases involv
ing blood cells in the systemic circulation, to which these carriers
are confined.
The frustrations associated with targeting drugs to specific sites
in the body using systems such as liposomes have led to research
to seek alternative carriers, such as insulin, that are biological in
nature and capable of exiting the circulation by virtue of their ability
to cross endothelial barriers via endocytosis and transcytosis. Par
allel research has focused on other biological carriers such as mono
clonal antibodies and certain glycoproteins that can recognize specific
determinants at their target cells. While these approaches are still
at their early stages of development and their role in controlled
drug delivery is therefore still uncertain, it is clear that the area
of controlled drug delivery is increasingly being based on molecular
biology.
The area of controlled drug delivery is also becoming broader
in scope in terms of routes of administration. Traditionally, con
trolled drug delivery systems were developed primarily for the oral
route and, to some extent, for the parenteral route. Recently,
there has been an explosion in research on drug delivery via the
skin, due primarily to the success of several transdermal devices in
sustaining drug delivery to the systemic circulation. Meanwhile, a
better understanding of the potential therapeutic role of biologically
active peptides and of their susceptibility to inactivation in the gas
trointestinal tract has stimulated research in delivering these substan
ces systemically via the nasal, buccal, rectal, and vaginal routes, the
so-called unconventional routes. In the short term, there will be
a need to fabricate systems perhaps more sophisticated than those
now available to deliver peptides via these routes as well as paren
teral routes. In the long term, it will be necessary to understand
the biochemistry and cell biology of these uncoventional routes, since
these may affect drug delivery system design. At the same time,
there will be a need to seek means to deliver these peptides orally.
This would require an enormous leap in our understanding of gross
physiology and cellular physiology, as well as of immunology of the
digestive system. Research has already begun in this area as exem
plified by the bioadhesion approach, whose initial aim is to prolong
the residence time of drugs in the gastrointestinal tract.
With this background in mind, we have organized the book into
three parts. Part I deals with the fundamentals of controlled drug
delivery. These include biological considerations of selected routes
of drug administration (Chapter 1), theory of mass transfer (Chap
ter 2), fundamentals of polymer science (Chapter 3), use of polymers
in controlled drug release (Chapter 4), pharmacokinetic/pharmacody
namic basis of controlled drug delivery (Chapter 5), bioavailability