USP-1087-固有溶出原文

1、1087APPARENTINTRINSICDISSOLUTION—DISSOLUTIONTESTINGPROCEDURESFORROTATINGDISKANDSTATIONARYDISKThisgeneralinformationchapterApparentIntrinsicDissolution—DissolutionTestingProceduresforRotatingDiskandStationaryDisk1087discussesthedeterminationofdissolutionratesfromnondisintegratingcompactsexposingafixedsurfaceareatoagivensolventmedium.Compact,asusedhere,isanondisintegratingmassresultingfromcompressionofthematerialundertestusingappropriatepressureconditions.Asinglesurfacehavingspecifiedphysicaldime。

2、nsionsispresentedfordissolution.Determinationoftherateofdissolutioncanbeimportantduringthecourseofthedevelopmentofnewchemicalentitiesbecauseitsometimespermitspredictionofpotentialbioavailabilityproblemsandmayalsobeusefultocharacterizecompendialarticlessuchasexcipientsordrugsubstances.Intrinsicdissolutionstudiesarecharacterizationstudiesandarenotreferencedinindividualmonographs.Informationprovidedinthisgeneralinformationchapterisintendedtobeadaptedviaaspecificprotocolappropriatetoaspecifiedmateri。

3、al.Dissolutionrategenerallyisexpressedasthemassofsoluteappearinginthedissolutionmediumperunittime(e.g.,masssec–1),butdissolutionfluxisexpressedastherateperunitarea(e.g.,masscm–2sec–1).Reportingdissolutionfluxispreferredbecauseitisnormalizedforsurfacearea,andforapuredrugsubstanceiscommonlycalledintrinsicdissolutionrate.Dissolutionrateisinfluencedbyintrinsicsolid-statepropertiessuchascrystallinestate,includingpolymorphsandsolvates,aswellasdegreeofnoncrystallinity.Numerousproceduresareavailableform。

4、odifyingthephysicochemicalpropertiesofchemicalentitiessothattheirsolubilityanddissolutionpropertiesareenhanced.Amongthesearecoprecipitatesandtheuseofracematesandenantiomericmixtures.Theeffectofimpuritiesassociatedwithamaterialcanalsosignificantlyalteritsdissolutionproperties.Dissolutionpropertiesarealsoinfluencedbyextrinsicfactorssuchassurfacearea,hydrodynamics,anddissolutionmediumproperties,includingsolvent(typicallywater),presenceofsurfactants,temperature,fluidviscosity,pH,buffertype,andbuffer。

5、strength.Rotatingdiskandstationarydiskdissolutionproceduresaresufficientlyversatiletoallowthestudyofcharacteristicsofcompoundsofpharmaceuticalinterestunderavarietyoftestconditions.Characteristicscommontobothapparatusesincludethefollowing:1.Theyareadaptabletousewithstandarddissolutiontestingstations,andbothuseatabletdietoholdthenondisintegratingcompactduringthedissolutiontest.2.Theyrelyoncompressionofthetestcompoundintoacompactthatdoesnotflakeorfallfreeduringthedissolutiontest.3.Asinglesurfaceofk。

6、nowngeometryandphysicaldimensionispresentedfordissolution.4.Thedieislocatedatafixedpositioninthevessel,whichdecreasesthevariationofhydrodynamicconditions.Adifferencebetweenthetwoproceduresisthesourceoffluidflowoverthedissolvingsurface.Inthecaseoftherotatingdiskprocedure,fluidflowisgeneratedbytherotationofthedieinaquiescentfluid,butfluidflowisgeneratedbyapaddleorotherstirringdeviceforthestationarydiskprocedure.EXPERIMENTALPROCEDURETheprocedureforcarryingoutdissolutionstudieswiththetwotypesofappar。

7、atusconsistsofpreparinganondisintegratingcompactofmaterialusingasuitablecompactiondevice,placingthecompactandsurroundingdieassemblyinasuitabledissolutionmedium,subjectingthecompacttothedesiredhydrodynamicsnearthecompactsurface,andmeasuringtheamountofdissolvedsoluteasafunctionoftime.Compactsaretypicallypreparedusinganapparatusthatconsistsofadie,anupperpunch,andalowersurfaceplatefabricatedoutofhardenedsteelorothermaterialthatallowsthecompressionofmaterialintoanondisintegratingcompact.Analternative。

8、compactionapparatusconsistsofadieandtwopunches.Otherconfigurationsthatachieveanondisintegratingcompactofconstantsurfaceareaalsomaybeused.Thenondisintegratingcompacttypicallyhasadiameterof0.2cmto1.5cm.CompactPreparationAttachthesmoothlowersurfaceplatetotheundersideofthedie,oralternatively,insertthelowerpunchusinganappropriateclampingsystem.Accuratelyweighaquantityofmaterialnecessarytoachieveanacceptablecompactandtransfertothediecavity.Placetheupperpunchintothediecavity,andcompressthepowderonahydr。

9、aulicpressatacompressionpressurerequiredtoformanondisintegratingcompactthatwillremaininthedieassemblyforthelengthofthetest.Compressionfor1minuteat15MPausuallyissufficientformanyorganiccrystallinecompounds,butalternativecompressionconditionsthatavoidtheformationofcapillariesshouldbeevaluated.Foragivensubstance,thecompactpreparation,onceoptimizedisstandardizedtofacilitatecomparisonofdifferentsamplesofthesubstance.Changesincrystallineformmayoccurduringcompression;therefore,confirmationofsolidstatef。

10、ormshouldbeperformedbypowderX-raydiffractionorothersimilartechnique.Removethesurfaceplateorlowerpunch.Removeloosepowderfromthesurfaceofthecompactanddiebyblowingcompressedairornitrogenoverthesurface.DissolutionMediumThechoiceofdissolutionmediumisanimportantconsideration.Wheneverpossible,testingshouldbeperformedundersinkconditionstoavoidartificiallyretardingthedissolutionrateduetoapproachofsolutesaturationofthemedium.Dissolutionmeasurementsaretypicallymadeinaqueousmedia.Toapproximateinvivocondition。