提高难溶性药物生物利用度的方法.pdf

Chapter13

EmergingTechnologiestoIncreasethe

BioavailabilityofPoorlyWater-SolubleDrugs

JustinR.HugheyandJamesW.McGinity

AbstractTheneedfornovelformulationandprocess-basedtechniquestoenhance

aqueoussolubilityhasincreasedsubstantiallyinrecentyears.Thisisprimarilydue

tothelimitationsoftraditionaltechniquessuchasphysicalandchemicalstabilityof

thedrugsubstanceortheneedfortoxicsolventsthatsometechniquesrequire.

Alternativesolubility-enhancementtechniqueshaveemergedinrecentyearstomit-

igateissuessuchasthese.Thepurposeofthischapteristodescribeemergingtech-

nologiesforsolubilityenhancement,allowingthereadertogainanunderstanding

oftheirutility.

13.1Introduction

Withtheadventofhigh-throughputscreeningtechniquesindrugdiscovery,thenum-

berofcompoundsreachingtheformulationdevelopmentstagehasincreaseddrasti-

cally(Lipinskietal.2001;Lipinski2004).Consequently,thishasgivenrisetoa

dramaticincreaseinthenumberofcompoundsthatexhibitpoorwatersolubility.

Thesedrugsubstancesmayalsoexhibitinstabilitiesorotherpropertiesthatseverely

limitacceptableformulationandprocessingtechniques.Thedevelopmentofnew

techniquestoimprovethebioavailabilityofcompoundssuchasthesehasbecomea

majorpointofinterestinthepharmaceuticalindustry.Inrecentyears,anumberof

novelformulationandprocessingtechniqueshaveemergedthatallowforthesuc-

cessfulprocessinganddeliveryofthesecompounds.Thesetechniquescanbebroadly

classifiedasthoseutilizingspecificequipmentorthosethataremoregeneraland

utilizecertaintypesorclassesofmaterials.

J.R.Hughey(*)•J.W.cGinity

PharmaceuticsDivision,CollegeofPharmacy,UniversityofTexasatAustin,

1UniversityStation,A1920,Austin,TX78712,USA

e-mail:justinhughey@utexas.edu

R.O.WilliamsIIIetal.(eds.),FormulatingPoorl