USP1092溶出度试验的开发和验证中英文对照版.docx
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USP1092溶出度试验的开发和验证中英文对照版.docx
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USP1092溶出度试验的开发和验证中英文对照版
(1092)溶出度试验的开辟和验证【中英文对照版】之青柳念文创作
INTRODUCTION
前言
Purpose
目标
TheDissolutionProcedure:
DevelopmentandValidation<1092>providesacomprehensiveapproachcoveringitemstoconsiderfordevelopingandvalidatingdissolutionproceduresandtheaccompanyinganalyticalprocedures.Itaddressestheuseofautomationthroughoutthetestandprovidesguidanceandcriteriaforvalidation.Italsoaddressesthetreatmentofthedatageneratedandtheinterpretationofacceptancecriteriaforimmediateandmodifiedreleasesolidoraldosageforms.
溶出实验:
开辟和验证(1092)指导原则提供了在溶出度方法开辟和验证过程中以及采取相应分析方法时需要思索的因素.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尺度.同时它还涉及对普通制剂和缓释制剂所生成的数据和承受尺度停止说明.
Scope
范围
Chapter<1092>addressesthedevelopmentandvalidationofdissolutionprocedures,withafocusonsolidoraldosageforms.Manyoftheconceptspresented,however,maybeapplicabletootherdosageformsandroutesofadministration.GeneralrecommendationsaregivenwiththeunderstandingthatmodificationsoftheapparatusandproceduresasgiveninUSPgeneralchaptersneedtobejustified.
<1092>章节讨论了溶出度实验的开辟和验证,重点是口服固体制剂.所提出的许多概念也可以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.
Theorganizationof<1092>followsthesequenceofactionsoftenperformedinthedevelopmentandvalidationofadissolutiontest.Thesectionsappearinthefollowingsequence.
在停止溶解度实验的开辟和验证时,常遵循指导原则<1092>,详细内容如下:
1.PRELIMINARYASSESSMENT(FOREARLYSTAGESOFPRODUCTDEVELOPMENT/DISSOLUTIONMETHODDEVELOPMENT)
1.前期评估(对产品开辟以及溶出度方法开辟的前期研究评估)
1.1PerformingFilterCompatibility
1.2DeterminingSolubilityandStabilityofDrugSubstanceinVariousMedia
1.3ChoosingaMediumandVolume
1.4ChoosinganApparatus
1.4溶出设备选择(桨法和篮法以及其他方法)
2.METHODDEVELOPMENT
2.1Deaeration
2.2Sinkers
2.3Agitation
2.4StudyDesign
2.4.1TimePoints
2.4.2Observations
2.4.3Sampling
2.4.4Cleaning
2.5DataHandling
2.6DissolutionProcedureAssessment
3.ANALYTICALFINISH
3.1SampleProcessing
3.1样品处理
3.2Filters
3.2过滤
3.3Centrifugation
3.3离心
3.4AnalyticalProcedure
3.4分析方法
3.5SpectrophotometricAnalysis
3.5光谱分析
3.6HPLC
4.AUTOMATION
4.1MediumPreparation
4.2SampleIntroductionandTiming
4.3SamplingandFiltration
4.4Cleaning
4.4清洗
4.5OperatingSoftwareandComputationofResults
5.VALIDATION
5.1Specificity/PlaceboInterference
5.1专属性/抚慰剂(辅料)干扰
5.2LinearityandRange
5.3Accuracy/Recovery
5.4Precision
5.4.1REPEATABILITYOFANALYSIS
5.4.2INTERMEDIATEPRECISION/RUGGEDNESS
5.4.3REPRODUCIBILITY
5.5Robustness
5.6StabilityofStandardandSampleSolutions
5.7ConsiderationsforAutomation
6.ACCEPTANCECRITERIA
6.1ImmediateReleaseDosageForms
6.2DelayedReleaseDosageForms
6.3ExtendedReleaseDosageForms
6.4MultipleDissolutionTests
6.5InterpretationofDissolutionResults
6.5.1IMMEDIATERELEASEDOSAGEFORMS
6.5.2DELAYEDRELEASEDOSAGEFORMS
6.5.3EXTENDEDRELEASEDOSAGEFORMS
1.PRELIMINARYASSESSMENT(FOREARLYSTAGESOFPRODUCTDEVELOPMENT/DISSOLUTIONMETHODDEVELOPMENT)
1. 前期评估(产品开辟/溶出度方法开辟的初期阶段)
Beforemethoddevelopmentcanbegin,itisimportanttocharacterizethemoleculesothatthefilter,medium,volumeofmedium,andapparatuscanbechosenproperlyinordertoevaluatetheperformanceofthedosageform.
在开端溶出方法开辟之前,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停止适当的筛选是非常重要的.
1.1PerformingFilterCompatibility
Filtrationisakeysamplepreparationstepinachievingaccuratetestresults.Thepurposeoffiltrationistoremoveundissolveddrugandexcipientsfromthewithdrawnsolution.Ifnotremovedfromthesamplesolution,particlesofthedrugwillcontinuetodissolveandcanbiastheresults.Therefore,filteringthedissolutionsamplesisusuallynecessaryandshouldbedoneimmediatelyifthefilterisnotpositionedonthecannula.
为获得准确试验成果,过滤是样品制备的一个关键步调.过滤的目标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,那末未溶解的药物颗粒将会继续溶解使试验成果出现偏差,因此,如果取样管中没有过滤器,应当即对溶出度样品停止过滤.
Filtrationalsoremovesinsolubleexcipientsthatmayotherwiseinterferewiththeanalyticalfinish.Selectionoftheproperfiltermaterialisimportantandshouldbeaccomplished,andexperimentallyjustified,earlyinthedevelopmentofthedissolutionprocedure.Importantcharacteristicstoconsiderwhenchoosingafiltermaterialaretype,filtersize,andporesize.Thefilterthatisselectedbasedonevaluationduringtheearlystagesofdissolutionproceduredevelopmentmayneedtobereconsideredatalatertimepoint.Requalificationhastobeconsideredafterachangeincompositionofthedrugproductorchangesinthequalityoftheingredients(e.g.particlesizeofmicrocrystallinecellulose).
过滤也可除去可以会干扰分析测定的不溶性辅料.选择适当的过滤资料是非常重要,应该在早期溶出方法开辟的过程中通过实验确定和完成.在选择滤膜时有需要重点思索滤膜的资料、型号和孔径大小.通常对早期阶段溶出方法开辟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质变更可以需要重新思索过滤器,(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途经滤器、过滤盘或玻璃过滤器、滤头或针头式过滤器.过滤资料必须与介质和药物相适合.罕见孔径大小范围:
0.20~70μm,如果需要也可使用其他孔径大小的过滤器.如果原料药的粒度很小(例如,微分化颗粒或纳米颗粒),找到一个合适的过滤器过滤这些小颗粒至今仍具有挑战性.
Adsorptionofthedrug(s)bythefiltermayoccurandneedstobeevaluated.Filtermaterialswillinteractwithdissolutionmediatoaffecttherecoveryoftheindividualsolutesandmustbeconsideredonacasebycasebasis.Differentfiltermaterialsexhibitdifferentdrugbindingproperties.Percentageofdruglossfromthefiltrateduetobindingmaybedependentonthedrugconcentration.Thereforetheadsorptiveinterferenceshouldbeevaluatedonsamplesolutionsatdifferentconcentrationsbracketingtheexpectedconcentrationrange.Wherethedrugadsorptionissaturable,discardinganinitialvolumeoffiltratemayallowthecollectionofasubsequentsolutionthatapproachestheoriginalsolutionconcentration.Alternativefiltermaterialsthatminimizeadsorptiveinterferencecanusuallybefound.Prewettingofthefilterwiththemediummaybenecessary.Inaddition,itisimportantthatleachablesfromthefilterdonotinterferewiththeanalyticalprocedure.Thiscanbeevaluatedbyanalyzingthefiltereddissolutionmediumandcomparingitwiththeunfilteredmedium.
过滤时可以会发生药物的吸附,需要停止评估.过滤资料将与溶出介质相互作用,影响每个溶质的回收率应该根据详细问题停止思索.分歧的过滤资料表示出与药物连系的分歧特性.由于药物与滤膜连系引起药物从滤液中损失的比例,可以依赖于药物浓度.因此,应采取预期浓度范围内分歧浓度的样品溶液来评估滤膜吸附干扰.由于药物吸附是可饱和的,弃去一定体积的初滤液,收集续滤液,以达到接近原来的溶液浓度的样品也是可取的.通常选择适合的过滤资料,最大限度地减少滤膜吸附干扰,润湿滤膜对减少吸附也是需要的.此外,过滤后的溶出物不干扰分析检测也是非常重要的,这可以通过过滤后的溶出介质过滤与未过滤的溶出介质停止比较,评估滤膜是否干扰分析测定.
Thefiltersizeshouldbebasedonthevolumetobewithdrawnandtheamountofparticlestobeseparated.Useofthecorrectfilterdimensionswillimprovethroughputandrecovery,andalsoreduceclogging.Useofalargefilterforsmallvolumefiltrationcanleadtolossofsamplethroughholdupvolume,whereasfiltrationthroughsmallfiltersizesneedshigherpressuresandlongertimes,andthefilterscanclogquickly.
根据要过滤样品溶液的体积以及样品溶液中颗粒的量选择滤膜孔径.使用正确的滤膜孔径将提高溶液的通过率和回收率,并减少滤膜堵塞.使用大孔径滤膜过滤小体积溶液,可以导致样品溶液损失量过大而收集不到所用样品量;使用小孔径滤膜过滤,需要更高的压力和较长的时间,而且溶液迅速堵塞滤膜.
FiltersusedforUSPApparatus4needspecialattentionbecausetheyareintegratedintheflowthroughprocess.Undissolvedparticlesmaydepositonthefilters,creatingresistancetotheflow.
USP仪器4中使用的过滤器需要特别注意,因为它们在活动过程中使用.不溶颗粒会沉积在过滤器,发生活动阻力.
Inthecaseofautomatedsystems,selectionofthefilterwithregardtomaterialandporesizecanbedoneinasimilarmannertomanualfiltration.Flowratethroughthefilterandcloggingmaybecriticalforfiltersusedinautomatedsystems.Experimental
verificationthatafilterisappropriatemaybeaccomplishedbycomparingtheresponsesforfilteredandunfilteredstandardandsamplesolutions.Thisisdonebyfirstpreparingasuitablestandardsolutionandasamplesolution.Forexample,prepareatypicaldissolutionsampleinabeakerandstirvigorouslywithamagneticstirrertodissolvethedrugloadcompletely.Forstandardsolutions,comparetheresultsforfilteredsolutions(afterdiscardingtheappropriatevolume)tothosefortheunfilteredsolutions.Forsamplesolutions,comparetheresultsforfilteredsolutions(afterdiscardingtheappropriatevolume)tothoseforcentrifuged,unfilteredsolutions.
在自动化系统的情况下,关于过滤器滤膜资料和孔径大小可以用近似的方式通过手动过滤停止选择.在自动化系统中通过过滤器的流量和过滤器的堵塞可以是至关重要的.通过试验比较过滤和未过滤的尺度溶液和样品溶液的含量不同,验证该过滤器是合适的.首先制备一个合适的尺度溶液和样品溶液.例如,在烧杯中制备一个尺度溶解样品,用磁力搅拌器搅拌使药物完全溶解.对于尺度溶液,比较过滤溶液(弃去的适当体积后)和未过滤溶液的含量测定成果;对于样品溶液,比较过滤(弃去适当体积后)、离心、未过滤样品溶液的含量测定成果.
1.2DeterminingSolubilityandStabilityofDrugSubstanceinVariousMedia
Physicalandchemicalcharacteristicsofthedrugsubstanceneedtobedeterminedaspartoftheprocessofselectingtheproperdissolutionmedium.Whendecidingthecompositionofthemediumfordissolutiontesting,itisimportanttoevaluatetheinfluenceofbuffers,pH,andifneeded,differentsurfactantsonthesolubilityandstabilityofthedrugsubstance.Solubilityofthedrugsubstanceisusuallyevaluatedbydeterminingthesaturationconcentrationofthedrugindifferentmediaat37°usingtheshakeflasksolubilitymethod(equilibriumsolubility).Toleveloutpotentialioneffectsbetweenthedrugandthebuffersusedinthemedia,mixturesofhydrochloricacidandsodiumhydroxideareusedtoperformsolubilityinvestigations;thisisinadditiontothetypicalbuffersolutions.Incertaincases,itmaybenecessarytoevaluatethesolubilityofthedrugattemperaturesotherthan37°(i.e.,25°).ThepHoftheclearsupernatantshouldbecheckedtodeterminewhetherthepHchangesduringthesolubilitytest.Alternativeapproachesforsolubilitydeterminationmayalsobeused.
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- USP1092 溶出度 试验 开发 验证 中英文 对照