USP-1087-固有溶出原文

1087APPARENTINTRINSICDISSOLUTION—DISSOLUTIONTESTINGPROCEDURESFORROTATINGDISKANDSTATIONARYDISKThisgeneralinformationchapterApparentIntrinsicDissolution—DissolutionTestingProceduresforRotatingDiskandStationaryDisk1087discussesthedeterminationofdissolutionratesfromnondisintegratingcompactsexposingafixedsurfaceareatoagivensolventmedium.Compact,asusedhere,isanondisintegratingmassresultingfromcompressionofthematerialundertestusingappropriatepressureconditions.Asinglesurfacehavingspecifiedphysicaldimensionsispresentedfordissolution.Determinationoftherateofdissolutioncanbeimportantduringthecourseofthedevelopmentofnewchemicalentitiesbecauseitsometimespermitspredictionofpotentialbioavailabilityproblemsandmayalsobeusefultocharacterizecompendialarticlessuchasexcipientsordrugsubstances.Intrinsicdissolutionstudiesarecharacterizationstudiesandarenotreferencedinindividualmonographs.Informationprovidedinthisgeneralinformationchapterisintendedtobeadaptedviaaspecificprotocolappropriatetoaspecifiedmaterial.Dissolutionrategenerallyisexpressedasthemassofsoluteappearinginthedissolutionmediumperunittime(e.g.,masssec–1),butdissolutionfluxisexpressedastherateperunitarea(e.g.,masscm–2sec–1).Reportingdissolutionfluxispreferredbecauseitisnormalizedforsurfacearea,andforapuredrugsubstanceiscommonlycalledintrinsicdissolutionrate.Dissolutionrateisinfluencedbyintrinsicsolid-statepropertiessuchascrystallinestate,includingpolymorphsandsolvates,aswellasdegreeofnoncrystallinity.Numerousproceduresareavailableformodifyingthephysicochemicalpropertiesofchemicalentitiessothattheirsolubilityanddissolutionpropertiesareenhanced.Amongthesearecoprecipitatesandtheuseofracematesandenantiomericmixtures.Theeffectofimpuritiesassociatedwithamaterialcanalsosignificantlyalteritsdissolutionproperties.Dissolutionpropertiesarealsoinfluencedbyextrinsicfactorssuchassurfacearea,hydrodynamics,anddissolutionmediumproperties,includingsolvent(typicallywater),presenceofsurfactants,temperature,fluidviscosity,pH,buffertype,andbufferstrength.Rotatingdiskandstationarydiskdissolutionproceduresaresufficientlyversatiletoallowthestudyofcharacteristicsofcompoundsofpharmaceuticalinterestunderavarietyoftestconditions.Characteristicscommontobothapparatusesincludethefollowing:1.Theyareadaptabletousewithstandarddissolutiontestingstations,andbothuseatabletdietoholdthenondisintegratingcompactduringthedissolutiontest.2.Theyrelyoncompressionofthetestcompoundintoacompactthatdoesnotflakeorfallfreeduringthedissolutiontest.3.Asinglesurfaceofknowngeometryandphysicaldimensionispresentedfordissolution.4.Thedieislocatedatafixedpositioninthevessel,whichdecreasesthevariationofhydrodynamicconditions.Adifferencebetweenthetwoproceduresisthesourceoffluidflowoverthedissolvingsurface.Inthecaseoftherotatingdiskprocedure,fluidflowisgeneratedbytherotationofthedieinaquiescentfluid,butfluidflowisgeneratedbyapaddleorotherstirringdeviceforthestationarydiskprocedure.EXPERIMENTALPROCEDURETheprocedureforcarryingoutdissolutionstudieswiththetwotypesofapparatusconsistsofpreparinganondisintegratingcompactofmaterialusingasuitablecompactiondevice,placingthecompactandsurroundingdieassemblyinasuitabledissolutionmedium,subjectingthecompacttothedesiredhydrodynamicsnearthecompactsurface,andmeasuringtheamountofdissolvedsoluteasafunctionoftime.Compactsaretypicallypreparedusinganapparatusthatconsistsofadie,anupperpunch,andalowersurfaceplatefabricatedoutofhardenedsteelorothermaterialthatallowsthecompressionofmaterialintoanondisintegratingcompact.Analternativecompactionapparatusconsistsofadieandtwopunches.Otherconfigurationsthatachieveanondisintegratingcompactofconstantsurfaceareaalsomaybeused.Thenondisintegratingcompacttypicallyhasadiameterof0.2cmto1.5cm.CompactPreparationAttachthesmoothlowersurfaceplatetotheundersideofthedie,oralternatively,insertthelowerpunchusinganappropriateclampingsystem.Accuratelyweighaquantityofmaterialnecessarytoachieveanacceptablecompactandtransfertothediecavity.Placetheupperpunchintothediecavity,andcompressthepowderonahydraulicpressatacompressionpressurerequiredtoformanondisintegratingcompactthatwillremaininthedieassemblyforthelengthofthetest.Compressionfor1minuteat15MPausuallyissufficientformanyorganiccrystallinecompounds,butalternativecompressionconditionsthatavoidtheformationofcapillariesshouldbeevaluated.Foragivensubstance,thecompactpreparation,onceoptimizedisstandardizedtofacilitatecomparisonofdifferentsamplesofthesubstance.Changesincrystallineformmayoccurduringcompression;therefore,confirmationofsolidstateformshouldbeperformedbypowderX-raydiffractionorothersimilartechnique.Removethesurfaceplateorlowerpunch.Removeloosepowderfromthesurfaceofthecompactanddiebyblowingcompressedairornitrogenoverthesurface.DissolutionMediumThechoiceofdissolutionmediumisanimportantconsideration.Wheneverpossible,testingshouldbeperformedundersinkconditionstoavoidartificiallyretardingthedissolutionrateduetoapproachofsolutesaturationofthemedium.Dissolutionmeasurementsaretypicallymadeinaqueousmedia.Toapproximateinvivocondition