Table Of Content9644: “9644_c000” — 2007/12/6 — 18:50 — page i — #1
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Contents
PrefacetotheFirstEdition ....................................................................... vii
PrefacetotheSecondEdition..................................................................... ix
Editor ................................................................................................ xi
Contributors ....................................................................................x.i.i.i.
Chapter1 Introduction.......................................................................... 1
Rong(Ron)Liu
Chapter2 SolubilityTheories................................................................... 5
StevenH.Neau
Chapter3 PredictionofSolubility.............................................................. 23
YishengChen,XiaohongQi,andRong(Ron)Liu
Chapter4 PreformulationAspectsofInsolubleCompoun..d.s............................... 61
Wei-Qin(Tony)TongandHongWen
Chapter5 Water-InsolubleDrugsandTheirPharmacokineticBehav.io..r.s................ 91
HonghuiZhou
Chapter6 RegulatoryAspectsofDissolutionforLowSolubilityDrugProdu.c.t.s......... 101
PradeepSathe,RobertA.Lionberger,SauLawrenceLee,andLawrenceX.Yu
Chapter7 FormulationStrategiesandPracticeUsedforDrugCandidateswith
Water-InsolublePropertiesforToxicology,Biology,andPharmacology
StudiesinDiscoverySuppo.r.t...................................................... 113
Lian-FengHuangandJinquanDong
Chapter8 ApplicationsofComplexationintheFormulationofInsolubleCompou.n.d..s. 133
Wei-Qin(Tony)TongandHongWen
Chapter9 SolubilizationUsingCosolventApproac..h........................................ 161
JayS.Trivedi
Chapter10 Emulsions,Microemulsions,andLipid-BasedDrugDeliverySystemsfor
DrugSolubilizationandDelivery—PartI:ParenteralApplicatio.n.s............. 195
JohnB.Cannon,YiShi,andPramodGupta
Chapter11 Emulsions,Microemulsions,andLipid-BasedDrugDeliverySystemsfor
DrugSolubilizationandDelivery—PartII:OralApplications.................... 227
JohnB.CannonandMichelleA.Long
Chapter12 MicellizationandDrugSolubilityEnhanceme.n..t................................ 255
Rong(Ron)Liu,Rose-MarieDannenfelser,andShoufengLi
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Chapter13 MicellizationandDrugSolubilityEnhancementPartII:PolymericMice.ll.e.s. 307
Rong(Ron)Liu,M.LairdForrest,andGlenS.Kwon
Chapter14 LiposomesinSolubilizatio.n........................................................ 375
Rong(Ron)Liu,JohnB.Cannon,andSophiaY.L.Paspal
Chapter15 PharmaceuticalSal.ts................................................................ 417
StevenH.Neau
Chapter16 ProdrugsforImprovedAqueousSolubil.it.y....................................... 437
StevenH.Neau
Chapter17 ParticleSizeReductio.n............................................................. 467
RobertW.Lee,JamesMcShane,J.MichaelShaw,RayW.Wood,andDineshB.Shenoy
Chapter18 DevelopmentofSolidDispersionforPoorlyWater-SolubleDr.u.g..s........... 499
MadhavVasanthavada,Wei-Qin(Tony)Tong,andAbuT.M.Serajuddin
Chapter19 AlterationoftheSolidStateoftheDrugSubstances:Polymorphs,Solvates,
andAmorphousForm.s.............................................................. 531
PaulB.MyrdalandMichaelJ.Jozwiakowski
Chapter20 PharmaceuticalPowderTechnology—BuildingthePyramidofKnowledge
andtheChallengeofFDA’sPATInitiativ.e........................................ 567
HansLeuenbergerandGabrieleBetz
Chapter21 SoftGelatinCapsulesDevelopme.n..t............................................. 589
S.EsmailTabibiandShankerL.Gupta
Chapter22 OralModi(cid:30)ed-ReleaseDrugDeliveryforWater-InsolubleDr.u.g..s............ 609
ShaolingLi,Nuo(Nolan)Wang,andRong(Ron)Liu
Chapter23 ScalableManufacturingofWater-InsolubleDrugProdu.c.t.s.................... 637
NitinP.PathakandRichard(Ruey-ching)Hwang
Index................................................................................................. 663
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Preface to the First Edition
This book has its origin in a training course, “The Role of Drug Solubility in Formulation
Development,” offered by theAmericanAssociation of Pharmaceutical Scientists, 6 years ago in
Chicago.Thecoursewasdesignedtohelpyoungpharmaceuticalscientistsandpharmacygraduate
students solve problems often encountered in dealing with water-insoluble drugs in their research
anddrugdevelopmentprograms,whichwaschairedbyDr.MaureenDonovanfromtheUniversityof
IowaCollegeofPharmacy,withlecturesbyDrs.StevenNeaufromUniversityofMissouri-Kansas
City College of Pharmacy, Pramod Gupta from Abbott Laboratories, and myself, then working
at American Cyanamid Company. Approximately 1 year after the course, I was approached by
InterpharmPresstodiscussthepublicationofabookonformulationsofwater-insolubledrugs.
As a pharmaceutical scientist working in the areas of drug discovery support, preformulation,
andformulationatAmericanCyanamidandAbbottforanumberofyears,Ihavecometoknowthe
importanceofutilizingsolubilizationtechniquesforsolvingdruginsolubilityproblemsinmydaily
work.Irealizethatthepharmaceuticalindustryhasanurgentneedforacollectionofexistingand
up-to-date knowledge and techniques on the solubilization of water-insoluble drugs. The diligent
workofallthecontributorsoverthepastyearshasmadethebookbecomeareality.Iwouldliketo
thankthemforalltheirhardworkandsacri(cid:30)ces.
Manydistinguishedscholarsinthe(cid:30)eldsofpharmaceuticalsandrelatedscienceshaveprovided
mewithalotofhelpfuldiscussionandvaluableinputduringmyeditingofthebook.Iwouldliketo
takethisopportunitytosincerelyacknowledgetheseindividualsfortheirmuchappreciatedhelp:
J.B.Cannon,PhD,AbbottLaboratories;P.P.Constantinides,PhD,SonusPharmaceuticals;
M.D. Donovan, PhD, University of Iowa; J.L. Ford, PhD, Liverpool John Moors
University,Liverpool,England.
S.G.Frank,PhD,OhioStateUniversity;J.K.Guillory,PhD,UniversityofIowa;R.J.Y.Ho,
PhD,UniversityofWashington;V.Kumar,PhD,UniversityofIowa.
M.Long,PhD,AbbottLaboratories;S.H.Neau,PhD,UniversityofMissouri-KansasCity;
J.T.Rubino, PhD,AmericanHomeProducts;A.Sinkula, PhD,WestPharmaceutical
Services; W.Q.Tong, PhD, Glaxo-Welcome, Inc.; V.P.Torchilin, PhD, Northeastern
University;M.R.Violante,PhD,Medisperse.
Y.Wei,PhD,R.P.Scherer;G.Zogra(cid:30),PhD,UniversityofWisconsin.
Andlast, butnottheleast, Iwouldliketothankmywife, PingChen, mydaughter, Catherine,
and my son, Eric, for their love, understanding, support, and encouragement during my work on
thisbook.
Rong(Ron)Liu
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Preface to the Second Edition
Ithasbeen7yearssincethebook“Water-InsolubleDrugFormulation”waspublishedintheyearof
2000.BoththepublisherandIhavereceivedmuchpositivefeedbackonthebookfromthereaders
since its publication. In the past decade, however, the (cid:30)eld of water-insoluble drug delivery has
seenmuchprogressandadvancement.Therefore,Ifeltobligatedtothereaderstoupdatethebook
with the latest development in this (cid:30)eld. In addition, I decided to broaden the scope of the book
to include areas of the science encompassing pharmacokinetics, early development, regulations,
manufacturing,andsoforth,inwater-insolubledrugstomakethisbookanevenmorecompleteand
comprehensivetoolfortheusers.ItisforthesereasonsthatIhavedecidedtorevisethebook.
In the second edition of the book, chapters in the (cid:30)rst edition have been updated (the chapter
thatdescribedsoliddispersionhasbeencompletelyrevised),andsixnewchaptershavebeenadded.
The new chapters are as follows: Water-Insoluble Drugs and Their Pharmacokinetic Behaviors;
RegulatoryAspects of Dissolution for Low-Solubility Drug Products; Formulation Strategies and
Practice Used for Drug Candidates with Water-Insoluble Properties for Toxicology, Biology, and
Pharmacology Studies in Discovery Support; Emulsion, Microemulsion, and Lipid-Based Drug
DeliverySystemsforDrugSolubilizationandDeliveryinOralApplications;OralModi(cid:30)ed-Release
Drug Delivery for Water-Insoluble Drugs; and Scalable Manufacturing of Water-Insoluble Drug
Products.
Besidesacknowledgingthecriticalreviewonvariouschaptersbymanydistinguishedscholars
inthe(cid:30)eldsofpharmaceuticalsandrelatedscienceswhowerementionedintheprefaceofthe(cid:30)rst
edition, Iwouldliketoappreciatethefollowingexpertswhohaveprovidedmewithconsiderable
amountsofhelpfuldiscussionandvaluableinputonthenewchaptersinthesecondedition:Parviz
Mojaveria, PhD, FCP, Quintiles Inc.; Ken Yamamoto, PhD, P(cid:30)zer Inc.; Marcus Brewster, PhD,
Johnson&JohnsonCompany;andLiangDong,PhD,Johnson&JohnsonCompany.
All the contributors and I hope the second edition will provide even more valuable informa-
tiontothescientistswhoneedhelpindealingwithwater-insolubledrugsduringtheirformulation
development.
Rong(Ron)Liu
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