溶出度检查法美国药典USP-711

1/20711DISSOLUTION溶出度(USP39-NF34Page540)GeneralchapterDissolution711isbeingharmonizedwiththecorrespondingtextsoftheEuropeanPharmacopoeiaand/ortheJapanesePharmacopoeia.Thesepharmacopeiashaveundertakentonotmakeanyunilateralchangetothisharmonizedchapter.通则711溶出度与欧盟药典和日本药典中的相应部分相统一。这三部药典承诺不做单方面的修改。PortionsofthepresentgeneralchaptertextthatarenationalUSPtext,andthereforenotpartoftheharmonizedtext,aremarkedwithsymbolstospecifythisfact.本章中的部分文字为本国USP内容，并没有与其他药典统一。此部分以（）标注。Thistestisprovidedtodeterminecompliancewiththedissolutionrequirementswherestatedintheindividualmonographfordosageformsadministeredorally.Inthisgeneralchapter,adosageunitisdefinedas1tabletor1capsuleortheamountspecified.Ofthetypesofapparatusdesignsdescribedherein,usetheonespecifiedintheindividualmonograph.Wherethelabelstatesthatanarticleisentericcoatedandadissolutionordisintegrationtestdoesnotspecificallystatethatitistobeappliedtodelayed-releasearticlesandisincludedintheindividualmonograph,theprocedureandinterpretationgivenforDelayed-ReleaseDosageFormsareapplied,unlessotherwisespecifiedintheindividualmonograph.本测试用于检测药品口服制剂的溶出度是否符合各论中的规定。本章中，除另有规定外，单位制剂定义为1片或1粒胶囊。对于本章中所述多种仪器，使用各论中规定的种类。除各论中另有规定外，如果检品是肠溶衣片且各论中的溶出度或崩解时限检查项下没有特别指出适用迟释剂的，使用本章中适用于迟释剂的流程和解释。FORDOSAGEFORMSCONTAININGORCOATEDWITHGELATIN涂有或包含明胶的剂型IfthedosageformcontaininggelatindoesnotmeetthecriteriaintheappropriateAcceptanceTable(seeInterpretation,Immediate-ReleaseDosageForms,Extended-ReleaseDosageForms,orDelayed-ReleaseDosageForms)becauseofevidenceofthepresenceofcross-linking,thedissolutionprocedureshouldberepeatedwiththeadditionofenzymestothemedium,asdescribedbelow,andthedissolutionresultsshouldbeevaluatedstartingatthefirststageoftheappropriateAcceptanceTable.Itisnotnecessarytocontinuetestingthroughthelaststage(upto24units)whencriteriaarenotmetduringthefirststagetesting,andevidenceofcross-linkingisobserved.如果剂型中含有明胶，其不符合验收表中的标准（见判断，速释制剂，延释制剂，缓释制剂），因为存在明胶交联结合作用，它的溶解过程与外加的媒介酶是重复的，见下面的描述，并且溶解结果可以通过适当的验收表的开始的第一阶段标准进行评估。如果溶出结果不满足第一阶段的测试标准，那么就没有必要继续测试到最后阶段，并且也证明了明胶交联结合作用的存在。2/20Gelatin,inthepresenceofcertaincompoundsand/orincertainstorageconditions,includingbutnotrestrictedtohighhumidityandtemperature,maypresentcross-linking.Apelliclemayformontheexternaland/orinternalsurfaceofthegelatincapsuleshelloronthedosageformthatpreventsthedrugfrombeingreleasedduringdissolutiontesting(seemoreinformationinCapsules—DissolutionTestingandRelatedQualityAttributes1094).明胶，存在于某一处方和/或某一储存条件下，如：高温高湿，可能存在明胶交联结合作用。在胶囊壳或其他剂型的外表面和/或内表面形成一层膜阻止溶出试验过程中药物的释放（见胶囊-溶出度检测和相关质量属性1094）。NOTE—Allreferencestoachapterabove1000areforinformationpurposesonly,foruseasahelpfulresource.Thesechaptersarenotmandatoryunlessexplicitlycalledoutforthisapplication.注-超过1000章节的所有引用应用的目的仅为提供参考信息。这些章节是非强制的，除非另有规定。DissolutionMediumwithpH≤4.0pH≤4.0的溶出介质Enzyme:Pepsin,activitydeterminedbytheprocedureinpurifiedpepsin,intheReagentSpecificationssection酶：胃蛋白酶，活性视试剂规格部分中的胃蛋白酶提纯过程而定。Amount:AquantityofpepsinthatresultsinanactivityofNMT750,000Units/Lofdissolutionmedium数量：一些胃蛋白酶对溶出介质提供NMT750,000单位/L的生物活性。DissolutionMediumwithpH4.0and6.8pH4.0和6.8的溶出介质Enzyme:Papain,activitydeterminedbytheAssaytestinthemonographforPapain;orbromelain,activitydeterminedbytheprocedureinbromelain,intheReagentSpecificationssection酶：木瓜蛋白酶，活性视木瓜蛋白酶专论中的分析测试而定；或菠萝蛋白酶，活性视试剂规格部分中的菠萝蛋白酶生产过程而定。Amount:AquantityofpapainthatresultsinanactivityofNMT550,000Units/Lofdissolutionmedium,oraquantityofbromelainthatresultsinanactivityofNMT30gelatin-digestingunits(GDU)/Lofdissolutionmedium数量：一些木瓜蛋白酶对溶出介质提供NMT550,000单位/L的生物活性；一些菠萝蛋白酶对溶出介质提供NMT30明胶消化单位/L的生物活性。DissolutionMediumwithpH≥6.8pH≥6.8的溶出介质Enzyme:Pancreatin,proteaseactivitydeterminedbytheprocedureinAssayforproteaseactivity(Caseindigestivepower)inthemonographforPancreatin酶：胰液素，蛋白酶活性视胰液素专论中的蛋白酶活性（酪蛋白消化能力）分析中的生产过程而定。Amount:AquantityofpancreatinthatresultsinaproteaseactivityofNMT2000Units/Lofdissolutionmedium数量：一些胰液素对溶出介质提供NMT550,000单位/L的蛋白酶活性。3/20DissolutionMediumContainingSurfactantorOtherIngredientsKnowntoDenaturetheEnzyme含有表面活性剂或其他已知成分变性酶的溶出介质Ifthedissolutionmediumcontainssurfactantorotheringredientsthatareknowntodenaturetheenzymeused,apretreatmentstepinthedissolutiontestingofthedosageformmaybeapplied.ThispretreatmentstepisdoneusingthespecifieddissolutionmediumwithoutthesurfactantortheingredientandwiththeadditionoftheappropriateamountofenzymeaccordingtothemediumpH.Theamountofenzymeaddedisappropriatetothevolumeofdissolutionmediumusedinthepretreatment.Toachievethespecifiedmediumvolumeforthefinaldissolutiontesting,thepretreatmentstepmaybeconductedwithasmallervolumeofmediumwithouttheingredientsuchthatthefinalvolumeisobtainedwhentheingredientisaddedattheendofthepretreatmentstep.Alloftheotherconditionsofthetest(apparatus,rotation,orflowrate)shouldremainasdescribedinthemethodormonograph.Typically,thedurationofthepretreatmentstepisNMT15min.Therequiredpretreatmenttimeshouldbeevaluatedonacase-by-casebasisandshouldbescientificallyjustified.Thistimeshouldbeincludedinthetotaltimeofthetest.Asanexample,ifthetotaltimeofthetestis45minand15minareusedin