Pharmaceutical Product Development: In Vitro-In Vivo Correlation

216 Pages·2007·2.13 MB·english

by  Murthy Chilukuri Dakshina

Pharmaceutical
Product Development
In Vitro-In VivoCorrelation
edited by
Dakshina Murthy Chilukuri
U.S. Food and Drug Administration (FDA)
Silver Spring, Maryland, U.S.A.
Gangadhar Sunkara
Novartis Pharmaceuticals
East Hanover, New Jersey, U.S.A.
David Young
AGI Therapeutics, Inc.
Columbia, Maryland, U.S.A.
New York London
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International Standard Book Number-10: 0-8493-3827-1 (Hardcover)
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Library of Congress Cataloging-in-Publication Data
Pharmaceutical product development / edited by Dakshina Murthy Chilukuri,
Gangadhar Sunkara, David Young.
p. ; cm. -- (Drugs and the pharmaceutical sciences ; v. 165)
Includes bibliographical references and index.
ISBN-13: 978-0-8493-3827-4 (hardcover : alk. paper)
ISBN-10: 0-8493-3827-1 (hardcover : alk. paper)
1. Drug development. 2. Drugs--Design. I. Chilukuri, Dakshina Murthy. II. Sunkara,
Gangadhar. III. Young, David, 1952- IV. Series.
[DNLM: 1. Drug Design. 2. Biological Availability. 3. Drug Evaluation,
Preclinical--methods. W1 DR893B v.165 2007 / QV 744 P5348 2007]
RM301.25.P395 2007
615’.1--dc22 2006050423
Visit the Informa Web site at
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To my mother, Chilukuri Shyamalamba, my (late) father,
Chilukuri RamachandraMurthy, and my wife, Ishwarya.
Dakshina Murthy Chilukuri
Idedicate thisbook to my father, Sri Prakasa Rao,
mother, Smt Ammajamma,wife, Nagalakshmi,and
son, Kiran Sai, for theirloving supportand caring.
Gangadhar Sunkara
Dedicated to my parents, Jack and Grace, my wonderfulwife, Karen,
and my twofantastic children, Bethany and Kyle.
David Young

Preface
Thedevelopmentofanewdrugfromthelaboratorytothepatienttakesbetween
10 to 15 years and costs hundreds of millions of dollars. The pharmaceutical
industry,inconjunctionwiththeregulatorybodiesacrosstheworld,hascontinu-
ouslysoughttoreducethetimetobringanewdrugtothemarketandreducethe
cost of drug development in order to maximize return on the investment and to
bring drugs to patients sooner. In the last two decades, the pharmaceutical
industry has experimented with and successfully adopted several integrated
and multidisciplinary approaches to achieve these reductions in development
efforts. These efforts were primarily made in the research areas of drug
compound screening, toxicological evaluation, and pharmaceutical product
development.
Owingtothescientificadvancesinthedevelopmentofchemicallycomplex
therapeutic agents (e.g., recombinant proteins/peptides, gene-based drugs)
intended for chronic therapies, there is a growing need for the continuous
development of suitable formulation either as conventional immediate release
oral formulation or controlled and/or continuous delivery via oral or parenteral
routes. As formulation and delivery strategies can enhance competitive advan-
tage for pharmaceutical companies, several chemical- and formulation-related
issues are driving the early- and late-stage development of drug products. In
the last few decades, significant medical advances have been made in the area
of drug delivery with the development of novel dosage forms. However, the
delivery of several classes of drugs continues to be a challenge, mainly due to
shortbiologicalhalf-lives,poormembranepermeability,andassociatedtoxicity
in the administered doses. Since more is now known about the relationship
betweenchemicalproperties and movement of drugs throughout the body, drug
discovery scientists are able to consider the pharmacokinetic properties of
agents much earlier in the drug/product development process.
Formulationdevelopmentconnectsseveralkeypreclinicalandclinicaltrials
to support the new drug application. Formulation development and optimization
involves varying excipient levels,processing methods, identifying discriminating
dissolutionmethods,andsubsequentscale-upofthefinalproduct.Thequantitative
andqualitativechangesinaformulationmayalterdrugreleaseandinvivoperform-
ance.Developingapharmaceuticalproductformulationinatimelymanner,while
v
vi Preface
ensuring quality, is a complex process that requires a systematic, science-based
approach. Thus, ever increasing pressures to reduce pharmaceutical product
developmenttimelineshaveresultedinpharmaceuticalscientistsinphysicalphar-
macy, pharmaceutics, and pharmacology working collaboratively to develop an
integrated approach of product development by addressing physicochemical and
biological issues early on. Such continuous collaborative effort has resulted in
thedevelopmentofanimportanttool:invitro–invivocorrelation.
It is expected that the readers of this book possess a basic knowledge of
biopharmaceutics and pharmacokinetics. The material presented in this text
serves the need of scientists who are keen on utilizing the principles of in
vitro–in vivo correlation in drug development. The objectives of this book are
three-fold: i) to serve as a useful tool to help guide scientists in research and
development by outlining the theory and successful practice of in vitro–
in vivo correlation, ii) to help formulators apply the tool in designing and
developing prototypes that enable selection of clinical formulations, and iii) to
help formulate strategy(ies) for product life-cycle management.
We would like to express our gratitude to the committed subject experts
who have graciously agreed to spend their valuable time in writing the various
chapters. Additional thanks to the publishers who have been supportive and
considerate in an effort to bring out the best book possible.
Dakshina Murthy Chilukuri
GangadharSunkara
David Young
Contents
Preface .... v
Contributors .... ix
1. Dissolution:Fundamentals of In Vitro Release and
the Biopharmaceutics Classification System ................ .. 1
Kevin C.Johnson
2. Pharmacokinetics: Basics of Drug Absorption from
a Biopharmaceutical Perspective ....... .................. . 29
Sandhya K.Apparaju and Srikanth C. Nallani
3. Approachesto Developing InVitro–In Vivo
Correlation Models ................. .................. . 47
Adrian Dunne
4. The Roleof In Vitro–In Vivo Correlation in Product
Development and Life Cycle Management ................. . 71
Shoufeng Li, MartinMueller-Zsigmondy,andHequnYin
5. In Vitro–InVivo Correlation ......... .................. 107
Nishit B.Modi
6. IVIVC for Oral Drug Delivery: Immediate Release and Extended
Release DosageForms ............... .................. 125
Colm Farrell andSiobhan Hayes
7. In Vitro–InVivo Correlation for ModifiedRelease
Parenteral Drug Delivery Systems ..... .................. 141
David Young
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8. In Vitro–InVivo Correlation: TransdermalDrug
Delivery Systems . .................. .................. 153
Ayyappa Chaturvedula andAjay K.Banga
9. In Vitro–InVivo Correlation: A Regulatory Perspective
with Case Studies .................. .................. 177
Patrick J. Marroum
Index .... 197
Contributors
Sandhya K. Apparaju Food and Drug Administration, Silver Spring,
Maryland, U.S.A.
AjayK.Banga CollegeofPharmacy,MercerUniversity,Atlanta,Georgia,
U.S.A.
AyyappaChaturvedula GlaxoSmithKline,Parsippany,NewJersey,U.S.A.
Adrian Dunne Schoolof Mathematical Sciences, University College
Dublin, Dublin, Ireland
ColmFarrell Department of Pharmacokinetics and Biopharmaceutics,
GloboMax—ICONDevelopment Solutions, Marlow, Bucks, U.K.
Siobhan Hayes Department of Pharmacokinetics and Biopharmaceutics,
GloboMax—ICONDevelopment Solutions, Marlow, Bucks, U.K.
Kevin C. Johnson Intellipharm, LLC, Niantic, Connecticut, U.S.A.
Shoufeng Li Pharmaceuticaland Analytical Development,Novartis
Pharmaceuticals Corporation, East Hanover, New Jersey, U.S.A.
Patrick J. Marroum Office of Clinical Pharmacology and
Biopharmaceutics,Center for Drug EvaluationandResearch,
Food andDrug Administration, Silver Spring, Maryland, U.S.A.
NishitB.Modi DepartmentofClinical Pharmacology, ALZA Corporation,
Mountain View, California, U.S.A.
Martin Mueller-Zsigmondy Pharmaceutical andAnalytical Development,
Novartis PharmaceuticalsAG, Basel, Switzerland
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