USP-1092-溶出度试验的开发和验证(中英文对照版)

（1092）溶出度试验的开发和验证【中英文对照版】INTRODUCTION前言Purpose目的TheDissolutionProcedure:DevelopmentandValidation1092providesacomprehensiveapproachcoveringitemstoconsiderfordevelopingandvalidatingdissolutionproceduresandtheaccompanyinganalyticalprocedures.Itaddressestheuseofautomationthroughoutthetestandprovidesguidanceandcriteriaforvalidation.Italsoaddressesthetreatmentofthedatageneratedandtheinterpretationofacceptancecriteriaforimmediate-andmodified-releasesolidoraldosageforms.溶出实验:开发和验证（1092）指导原则提供了在溶出度方法开发和验证过程中以及采用相应分析方法时需要考虑的因素。本指导原则贯穿溶出度实验的全部过程，并对方法提供了指导和验证标准。同时它还涉及对普通制剂和缓释制剂所生成的数据和接受标准进行说明。Scope范围Chapter1092addressesthedevelopmentandvalidationofdissolutionprocedures,withafocusonsolidoraldosageforms.Manyoftheconceptspresented,however,maybeapplicabletootherdosageformsandroutesofadministration.GeneralrecommendationsaregivenwiththeunderstandingthatmodificationsoftheapparatusandproceduresasgiveninUSPgeneralchaptersneedtobejustified.1092章节讨论了溶出度实验的开发和验证，重点是口服固体制剂。所提出的许多概念也可能适用于其他剂型和给药途径。关于设备和方法的修改部分在USP通则中给出了合理的说明。Theorganizationof1092followsthesequenceofactionsoftenperformedinthedevelopmentandvalidationofadissolutiontest.Thesectionsappearinthefollowingsequence.在进行溶解度实验的开发和验证时，常遵循指导原则1092，具体内容如下：1.PRELIMINARYASSESSMENT(FOREARLYSTAGESOFPRODUCTDEVELOPMENT/DISSOLUTIONMETHODDEVELOPMENT)1.前期评估（对产品开发以及溶出度方法开发的前期研究评估）1.1PerformingFilterCompatibility1.1滤膜相容性研究1.2DeterminingSolubilityandStabilityofDrugSubstanceinVariousMedia1.2原料药在不同溶出介质中溶解度测定和稳定性研究1.3ChoosingaMediumandVolume1.3溶出介质和体积选择1.4ChoosinganApparatus1.4溶出设备选择（桨法和篮法以及其他方法）2.METHODDEVELOPMENT2.方法开发2.1Deaeration2.1脱气2.2Sinkers2.2沉降篮2.3Agitation2.3转速2.4StudyDesign2.4研究设计2.4.1TimePoints2.4.1取样时间点2.4.2Observations2.4.2观察2.4.3Sampling2.4.3取样2.4.4Cleaning2.4.4清洗2.5DataHandling2.5数据处理2.6DissolutionProcedureAssessment2.6溶出方法评估3.ANALYTICALFINISH3.完成分析3.1SampleProcessing3.1样品处理3.2Filters3.2过滤3.3Centrifugation3.3离心3.4AnalyticalProcedure3.4分析方法3.5SpectrophotometricAnalysis3.5光谱分析3.6HPLC3.6HPLC法4.AUTOMATION4.自动化4.1MediumPreparation4.1介质的配制4.2SampleIntroductionandTiming4.2定时进样4.3SamplingandFiltration4.3取样和过滤4.4Cleaning4.4清洗4.5OperatingSoftwareandComputationofResults4.5操作软件和计算的结果5.VALIDATION5.验证5.1Specificity/PlaceboInterference5.1专属性/安慰剂（辅料）干扰5.2LinearityandRange5.2线性和范围5.3Accuracy/Recovery5.3准确度/回收率5.4Precision5.4精密度5.4.1REPEATABILITYOFANALYSIS5.4.1重复性5.4.2INTERMEDIATEPRECISION/RUGGEDNESS5.4.2中间精密度/耐用性5.4.3REPRODUCIBILITY5.4.3重现性5.5Robustness5.5耐用性5.6StabilityofStandardandSampleSolutions5.6样品溶液和标准溶液的稳定性5.7ConsiderationsforAutomation5.7自动操作注意事项6.ACCEPTANCECRITERIA6.可接受标准6.1Immediate-ReleaseDosageForms6.1速释剂型6.2Delayed-ReleaseDosageForms6.2延迟释放剂型6.3Extended-ReleaseDosageForms6.3延长释放剂型6.4MultipleDissolutionTests6.4多个溶解度试验6.5InterpretationofDissolutionResults6.5溶出结果说明6.5.1IMMEDIATE-RELEASEDOSAGEFORMS6.5.1即时释放剂型6.5.2DELAYED-RELEASEDOSAGEFORMS6.5.2延迟释放剂型6.5.3EXTENDED-RELEASEDOSAGEFORMS6.5.3延长释放剂型1.PRELIMINARYASSESSMENT(FOREARLYSTAGESOFPRODUCTDEVELOPMENT/DISSOLUTIONMETHODDEVELOPMENT)1.前期评估（产品开发/溶出度方法开发的初期阶段）Beforemethoddevelopmentcanbegin,itisimportanttocharacterizethemoleculesothatthefilter,medium,volumeofmedium,andapparatuscanbechosenproperlyinordertoevaluatetheperformanceofthedosageform.在开始溶出方法开发之前，我们对用以评价制剂溶出行为的滤膜、溶出介质、溶出介质体积和溶出设备进行适当的筛选是非常重要的。1.1PerformingFilterCompatibility1.1滤膜相容性研究Filtrationisakeysample-preparationstepinachievingaccuratetestresults.Thepurposeoffiltrationistoremoveundissolveddrugandexcipientsfromthewithdrawnsolution.Ifnotremovedfromthesamplesolution,particlesofthedrugwillcontinuetodissolveandcanbiastheresults.Therefore,filteringthedissolutionsamplesisusuallynecessaryandshouldbedoneimmediatelyifthefilterisnotpositionedonthecannula.为获得准确试验结果，过滤是样品制备的一个关键步骤。过滤的目的是为了除去溶出液中未溶解的药物和辅料。如果不把未溶解的药物和辅料从样品溶液中除去，那么未溶解的药物颗粒将会继续溶解使试验结果出现偏差，因此，如果取样管中没有过滤器，应立即对溶出度样品进行过滤。Filtrationalsoremovesinsolubleexcipientsthatmayotherwiseinterferewiththeanalyticalfinish.Selectionoftheproperfiltermaterialisimportantandshouldbeaccomplished,andexperimentallyjustified,earlyinthedevelopmentofthedissolutionprocedure.Importantcharacteristicstoconsiderwhenchoosingafiltermaterialaretype,filtersize,andporesize.Thefilterthatisselectedbasedonevaluationduringtheearlystagesofdissolutionproceduredevelopmentmayneedtobereconsideredatalatertimepoint.Requalificationhastobeconsideredafterachangeincompositionofthedrugproductorchangesinthequalityoftheingredients(e.g.particlesizeofmicrocrystallinecellulose).过滤也可除去可能会干扰分析测定的不溶性辅料。选择适当的过滤材料是非常重要，应该在早期溶出方法开发的过程中通过实验确定和完成。在选择滤膜时有必要重点考虑滤膜的材料、型号和孔径大小。通常对早期阶段溶出方法开发过程的评价选择过滤器，但在后期试验中如果制剂成分改变或组成成分质量变化可能需要重新考虑过滤器，（例如：微晶纤维素粒径的改变）。Examplesoffiltersusedindissolutiontestingcanbecannulafilters,filterdisksorfrits,filtertips,orsyringefilters.Thefiltermaterialhastobecompatiblewiththemediaandthedrug.Commonporesizesrangefrom0.20to70mm,however,filtersofotherporesizescanbeusedasneeded.Ifthedrugsubstanceparticlesizeisverysmall(e.g.,micronizedornanoparticles),itcanbechallengingtofindafilterporesizethatexcludesthesesmallparticles.用于溶出试验的过滤器有管路过滤器、过滤盘或玻璃过滤器、滤头或针头式过滤器。过滤材料必须与介质和药物相适合。常见孔径