溶出度检查法美国药典USP-711

1、DISSOLUTION溶出度(USP39-NF34Page540)GeneralchapterDissolutionv711isbeingharmonizedwiththecorrespondingtextsoftheEuropeanPharmacopoeiaand/ortheJapanesePharmacopoeia.Thesepharmacopeiashaveundertakentonotmakeanyunilateralchangetothisharmonizedchapter.通则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。Portionsofthep

2、resentgeneralchaptertextthatarenationalUSPtext,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。Thistestisprovidedtodeterminecompliancewiththedissolutionrequirements+wherestatedintheindividualmonograph*fordosageformsadministeredorally

3、.Inthisgeneralchapter,adosageunitisdefinedas1tabletor1capsuleortheamountspecified.+Ofthetypesofapparatusdesignsdescribedherein,usetheonespecifiedintheindividualmonograph.Wherethelabelstatesthatanarticleisentericcoatedandadissolutionordisintegrationtestdoesnotspecificallystatethatitistobeappliedtodel

4、ayed-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

5、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)becauseofevidenceofthepresenc

6、eofcross-linking,thedissolutionprocedureshouldberepeatedwiththeadditionofenzymestothemedium,asdescribedbelow,andthedissolutionresultsshouldbeevaluatedstartingatthefirststageoftheappropriateAcceptanceTable.Itisnotnecessarytocontinuetestingthroughthelaststage(upto24units)whencriteriaarenotmetduringthe

7、firststagetesting,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。Gelatin,inthepresenceofcertaincompoundsand/orincertainstorageconditions,including

8、butnotrestrictedtohighhumidityandtemperature,maypresentcross-linking.Apelliclemayformontheexternaland/orinternalsurfaceofthegelatincapsuleshelloronthedosageformthatpreventsthedrugfrombeingreleasedduringdissolutiontesting(seemoreinformationinCapsulesDissolutionTestingandRelatedQualityAttributesvl094)

9、.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)。NoteAllreferencestoachapteraboveareforinformationpurposesonly,foruseasahelpfulresource.Thesechaptersarenotmandatoryunlessexplicitlycalledoutforthisapplication.注-超过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。

10、DissolutionMediumwithpH4.0pH4.0and4.0和6.8pH6.8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

11、/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。DissolutionMediumContainingSurfactantorOtherIngredientsKnowntoDenaturetheEnzyme含有表面活性剂或其他已知成分变性酶的溶出介质Ifthedissolutionmediumcontainssurfactantorotheringredientsthatareknowntodenaturetheenzymeused,apretreatmentstepinthedissolutiontestingofthedos

12、ageformmaybeapplied.ThispretreatmentstepisdoneusingthespecifieddissolutionmediumwithoutthesurfactantortheingredientandwiththeadditionoftheappropriateamountofenzymeaccordingtothemediumpH.Theamountofenzymeaddedisappropriatetothevolumeofdissolutionmediumusedinthepretreatment.Toachievethespecifiedmedium

13、volumeforthefinaldissolutiontesting,thepretreatmentstepmaybeconductedwithasmallervolumeofmediumwithouttheingredientsuchthatthefinalvolumeisobtainedwhentheingredientisaddedattheendofthepretreatmentstep.Alloftheotherconditionsofthetest（apparatus,rotation,orflowrate）shouldremainasdescribedinthemethodor

14、monograph.Typically,thedurationofthepretreatmentstepisNMT15min.Therequiredpretreatmenttimeshouldbeevaluatedonacase-by-casebasisandshouldbescientificallyjustified.Thistimeshouldbeincludedinthetotaltimeofthetest.Asanexample,讦thetotaltimeofthetestis45minand15minareusedinthepretreatmentstep,thetestwillc

15、ontinuefor30minaftertheadditionoftheingredient.如果溶出介质中添加了表面活性剂或其他已知成分的变性酶，那么此溶出实验就要把预处理步骤考虑进去。预处理过程就是是根据溶出介质的pH来确定加入酶的量，此处的溶出介质不含有表面活性剂和原料。酶加入的量要适合预处理所用的溶出介质的体积。为了达到最终溶出试验所需要的特定的溶出介质的体积，预处理阶段所用的溶出介质（不含原料）的体积要稍微小点，如此在预处理最后阶段加入原料的时候方可获得最终的溶出介质体积。其他所有的测试条件（如：设备、转速、流速）应该与方法或专论中描述的一致。通常预处理阶段的持续时间为NMT15mi

16、n。所需的预处理时间应该根据具体案例具体分析，且应该科学、合理。预处理时间应该包含在实验的总时间里。例如，如果实验的总时间为45min,预处理时间为15min，那么加入原料后实验还要继续进行30min。USPReferenceStandards11一USPPrednisoneTablets.RSUSP参考标准-USP强的松片RS。APPARATUS仪器Apparatus1（BasketApparatus）第1法（篮法）Theassemblyconsistsofthefollowing:avessel,whichmaybecovered,andmadeofglassorotherinert,tr

17、ansparentmaterial；amotor;ametallicdriveshaft;andacylindricalbasket.Thevesselispartiallyimmersedinasuitablewaterbathofanyconvenientsizeorheatedbyasuitabledevice,suchasaheatingjacket.Thewaterbathorheatingdevicepermitsholdingthetemperatureinsidethevesselat370.5duringthetestandkeepsthebathfluidinconstan

18、t,smoothmotion.Nopartoftheassembly,includingtheenvironmentinwhichtheassemblyisplaced,contributessignificantmotion,agitation,orvibrationbeyondthatduetothesmoothlyrotating,stirringelement.Anapparatusthatpermitsobservationofthespecimenandofthestirringelementduringthetestispreferable.Thevesseliscylindri

19、cal,withahemisphericalbottomand*withoneofthefollowingdimensionsandcapacities:foranominal*capacityof1L,theheightis160210mm,anditsinsidediameteris98106mm;*foranominalcapacityof2L,theheightis280300mm,anditsinsidediameteris98-106mm;andforanominalcapacityof4L,theheightis28300mm,anditsinsidediameteris1451

20、55mm+.Itssidesareflangedatthetop.Afittedcovermaybeusedtoretardevaporation.2TheshaftispositionedsothatitsaxisisNMT2mmatanypointfromtheverticalaxisofthevesselandrotatessmoothlyandwithoutsignificantwobblethatcouldaffecttheresults.Aspeed-regulatingdeviceisusedthatallowstheshaftrotationspeedtobeselecteda

21、ndmaintainedatthespecifiedrate+givenintheindividualmonograph*within4%.设备由下列部分组成：有盖或无盖的溶出杯，由玻璃或其他惰性的透明材料1制成；马达；转轴；转篮。溶出杯部分浸没在合适大小的水浴中，或者由合适的装置加热，例如电热套。水浴或加热装置需能在测试过程中将杯内温度保持在370.5C，并且容许杯内液体持续、平缓的流动。整个仪器包括周围的环境，除了平稳转动的搅拌部件，不得有明显的运动，搅动或振动。仪器最好能允许在检测过程中能够观察到检品和搅拌部件。溶出杯为圆柱形，底部为半球形，尺寸和容积如下：名义容积1L的，高160210

22、mm，内径98106mm；名义容积2L的，高280300mm，内径98106mm；名义容积4L的，高280300mm，内径145155mm。内壁顶部有缘。可以使用合适的盖子减缓溶剂蒸发2。转轴与溶出杯的纵轴在任意部位不得相差差过2mm,转动平滑，无明显摇晃以至于影响检测结果。速度调节装置控制转轴的转速，并可维持*在各论中规定值*的4%范围内。Shaftandbasketcomponentsofthestirringelementarefabricatedofstainlesssteel,type316,orotherinertmaterial,tothespecificationsshowni

23、nFigure1.Abaskethavingagoldcoatingofabout0.0001inch(2.5pm)thickmaybeused.Adosageunitisplacedinadrybasketatthebeginningofeachtest.Thedistancebetweentheinsidebottomofthevesselandthebottomofthebasketismaintainedat252mmduringthetest.转轴和篮筐组件由316号不锈钢或者其他惰性材料制成，尺寸如图1所示。可使用镀金厚度0.0001英寸(2.5pm)的篮筐。开始检测时，将一剂药品

24、至于干燥的篮筐中。在测试过程中，溶出杯底部到篮筐底部的距离应保持在252mm。ClearopeningVenthole2.0+0.5mmdiameterFigure1.Basketstirringelement.图1.ClearopeningVenthole2.0+0.5mmdiameterFigure1.Basketstirringelement.图1.转篮组成Apparatus2（PaddleApparatus第2法（桨法）Retentionspringwith3langson120centersScreenO.D.22.21.0mmScreenwithweldedseam：0,27-0,

25、31mmwiredhnneterwithwiretip轻ring主of0.36-0.44mm.Note一Afterwelding,thescreenmaybeslightlyaltoredJis11.0mmwlienthepartisrotatedoncenterInesxiswithbasketmeuntmd.UsetheassemblyfromApparatus1,exceptthatapaddleformedfromabladeandashaftisusedasthestirringelement.TheshaftispositionedsothatitsaxisisNMT2mmfrom

26、theverticalaxisofthevesselatanypointandrotatessmoothlywithoutsignificantwobblethatcouldaffecttheresults.Theverticalcenterlineofthebladepassesthroughtheaxisoftheshaftsothatthebottomofthebladeisflushwiththebottomoftheshaft.ThepaddleconformstothespecificationsshowninFigure2.Thedistanceof252mmbetweenthe

27、bottomofthebladeandtheinsidebottomofthevesselismaintainedduringthetest.Themetallicorsuitablyinert,rigidbladeandshaftcomposeasingleentity.Asuitabletwo-part,detachabledesignmaybeused,providedthattheassemblyremainsfirmlyengagedduringthetest.Thepaddlebladeandshaftmaybecoatedwithasuitablecoatingsoastomak

28、ebothoftheminert.Thedosageunitisallowedtosinktothebottomofthevesselbeforerotationofthebladeisstarted.Asmall,loosepieceofnonreactivematerial,suchasNMTafewturnsofwirehelix,maybeattachedtodosageunitsthatwouldotherwisefloat.AnalternativesinkerdeviceisshowninFigure2a.Othervalidatedsinkerdevicesmaybeused.

29、使用第1法中的设备，除了使用一个由叶片和转轴组成的桨作为搅拌单元。转轴与溶出杯的纵轴在任意部位不得相差差过2mm,转动平滑，无明显摇晃以至于影响检测结果。叶片的垂直中性线穿过转轴的轴线，叶片的下缘与转轴底部平齐。桨的尺寸应符合图2中的规定。在测试过程中，叶片底部与溶出杯底部的距离应保持在252mm。金属或硬质的叶片和转轴应是一个整体。两部分组合的设计也可以使用，只要组件在检测过程中牢固固定在一起。可以在桨叶和转轴上涂布合适的涂层以使其为惰性。在桨叶开始旋转前，将一剂药品沉至溶出杯底。如果药剂浮在页面上，可以在其上附着一个惰性，松弛的小部件，例如几圈线圈，使其沉没。图2是一种可替代使用的沉子。其

30、他经验证的沉子也可以使用。NotesAandBdimensionsarenottovarymorethan0.5mmwhenpartisrdtatAdnncenterlineaxis.TolerancesareNotesAandBdimensionsarenottovarymorethan0.5mmwhenpartisrdtatAdnncenterlineaxis.Tolerancesare1.0mmunlessotherwisestated.4.0Il.0mmFigure2.Paddlestirringelement.图2.搅拌桨组成3,5-4,0.5-4.0A;Acid-resistant

31、wirecla?pB;ftcid-resistantwiresupportFigure2a.Alternativesinker.Alldimensionsareexpressedinmm.图2a.可选的沉降篮(单位均为mm)Apparatus3(ReciprocatingCylinder)3法(往复圆筒法)NOTACCEPTEDBYTHEJAPANESEPHARMACOPOEIA日本药典未收录Theassemblyconsistsofasetofcylindrical,flat-bottomedglassvessels;asetofglassreciprocatingcylinders;ine

32、rtfittings(stainlesssteeltype316orothersuitablematerial),andscreensthataremadeofsuitablenonsorbingandnonreactivematerialandthataredesignedtofitthetopsandbottomsofthereciprocatingcylinders;andamotoranddriveassemblytoreciprocatethecylindersverticallyinsidethevessels;ifdesired,indexthereciprocatingcyli

33、ndershorizontallytoadifferentrowofvessels.Thevesselsarepartiallyimmersedinasuitablewaterbathofanyconvenientsizethatpermitsholdingthetemperatureat370.5duringthetest.Nopartoftheassembly,includingtheenvironmentinwhichtheassemblyisplaced,contributessignificantmotion,agitation,orvibrationbeyondthatduetot

34、hesmooth,verticallyreciprocatingcylinder.Adeviceisusedthatallowsthereciprocationratetobeselectedandmaintainedatthespecifieddiprate*givenintheindividualmonograph*within5%.Anapparatusthatpermitsobservationofthespecimensandreciprocatingcylindersispreferable.Thevesselsareprovidedwithevaporationcapsthatr

35、emaininplaceforthedurationofthetest.ThecomponentsconformtothedimensionsshowninFigure3unlessotherwisespecified+intheindividualmonograph*.所用设备包含一套圆柱形平底玻璃杯；一套玻璃往复圆筒；惰性配件(316号不锈钢或其他合适的材质)；由合适的非吸附，不反应材料制成的筛网，挡在往复圆筒的上下两端；一套马达和传动装置，将圆筒在玻璃杯中垂直往复运动，如果需要，也可以将往复圆筒平行移至另一行玻璃杯中。玻璃杯部分浸没在合适尺寸的水浴中，水浴温度保持在370.5Co仪器的任

36、何部件，以及仪器所处的环境，都不应当引起明显的移动，搅动，振动，除了平滑的垂直往复运动的圆筒。使用设备维持往复速度*在各论中所规定*值的5%范围内。仪器最好可以在检测过程中观察到样品和往复圆筒。玻璃杯配有蒸发帽，在检测中一直盖在玻璃杯上。除另有规定外辛，各部分的尺寸如图3所示。50,S-|1Airholes3,90.1diameterEvaporationcapIii38.116-8diameterType316stainlesssteelAirholes3.90.1diameterMeshscreen50,S-|1Airholes3,90.1diameterEvaporationcapIii

37、38.116-8diameterType316stainlesssteelAirholes3.90.1diameterMeshscreenAGlassreciprocatingcylinderMeshscreen471.4+i吨一Gia$Figure3.Apparatus3（reciprocatingcylinder）.图3.图3第3法（往复圆筒法）设备Apparatus4（Flow-ThroughCell第4法（流通池法）TheassemblyconsistsofareservoirandapumpfortheDissolutionmedium;aflowthroughcell;andawa

38、terbaththatmaintainstheDissolutionmediumat370.5.Usethespecifiedcellsize+asgivenintheindividualmonograph*.所用设备包含一个溶出介质的容器和相应的泵，一个流通池和水浴。水浴将溶出介质保持在370.5C。使用*各论中规定*的尺寸。ThepumpforcestheDissolutionmediumupwardthroughtheflow-throughcell.Thepumphasadeliveryrangebetween240and960mL/h,withstandardflowratesof4

39、,8,and16mL/min.Itmustdeliveraconstantflow(土5%ofthenominalflowrate);theflowprofileissinusoidalwithapulsationof12010pulses/min.Apumpwithoutpulsationmayalsobeused.Dissolutiontestproceduresusingaflow-throughcellmustbecharacterizedwithrespecttorateandanypulsation.泵将溶出介质推动，向上通过流通池。泵的传输能力在240到960mL每小时之间，标准

40、速率为4，&16mL每分钟。泵的流速必须均匀(名义流量的5%以内)。泵的流量特性曲线应为正弦波，脉冲为每分钟12010冲。无脉冲泵也可以使用。使用流通池法的溶出度测试必须对应特定的流速和脉冲。Theflow-throughcell(seeFigure4andFigure5),oftransparentandinertmaterial,ismountedverticallywithafiltersystem(specifiedintheindividualmonograph)thatpreventsescapeofundissolvedparticlesfromthetopofthecell;s

41、tandardcelldiametersare12and22.6mm;thebottomconeisusuallyfilledwithsmallglassbeadsofabout1-mmdiameterwithonebeadofabout5mm,positionedattheapextoprotectthefluidentrytube;andatabletholder(seeFigure4andFigure5)isavailableforpositioningofspecialdosageforms,e.g.,inlaytablets.Thecellisimmersedinawaterbath

42、,andthetemperatureismaintainedat370.5.由透明且惰性材料制成的流通池(见图4和图5)垂直安放，配有过滤系统(在各论中规定)以防止未溶解的颗粒从流通池顶部逸出。标准的流通池直径为12和22.6mm。底部的锥形通常填有直径约1mm的小玻璃珠，其中一颗约5mm大的玻璃珠置于顶点处，以保护液体输入管。流通池配有药片架(见图4和图5)一满足特殊制剂的需要，如泡腾片。流通池浸没在370.5C的水浴中。0=diametertabletsandcapsules(top);tabletholderforthelargecell(bottom).(Allmeasurements

43、areexpressedinmmunlessnotedotherwise.)图4.第4法设备，盛装片剂和胶囊的大流通池(上)大药片架(下)(除另有说明，所有尺寸单位为mm。)tabletsandcapsules(top);tabletholderforthesmallcell(bottom).(Allmeasurementsareexpressedinmmunlessnotedotherwise.)图5第4法设备，盛装片剂和胶囊的小流通池(上)，小药片架(下)。(除另有说明，所有尺寸单位为mm。)TheapparatususesaclampmechanismandtwoO-ringstoass

44、emblethecell.Thepumpisseparatedfromthedissolutionunittoshieldthelatteragainstanyvibrationsoriginatingfromthepump.Thepositionofthepumpshouldnotbeonalevelhigherthanthereservoirflasks.Tubeconnectionsareasshortaspossible.Usesuitablyinerttubing,suchaspolytef,withabouta1.6-mminnerdiameterandchemicallyiner

45、t,flanged-endconnections.流通池使用一个架子和2个O形圈固定。泵与溶出单元分开，以防止泵的振动干扰到后者。泵的水平位置不得高于溶出介质容器。管线连接尽可能短。使用合适的惰性管线，如聚四氟乙烯，内径1.6mm。法兰连接也应为化学惰性。APPARATUSSUITABILITY设备适用性Thedeterminationofsuitabilityofatestassemblytoperformdissolutiontestingmustincludeconformancetothedimensionsandtolerancesoftheapparatusasgivenabove

46、.Inaddition,criticaltestparametersthathavetobemonitoredperiodicallyduringuseincludevolumeandtemperatureoftheDissolutionmedium,rotationspeed(Apparatus1andApparatus2),diprate(Apparatus3),andflowrateofmedium(Apparatus4).溶出度测试仪器的适用性必须包括与上述各仪器在尺寸和限度上的一致性。另外，必须在使用过程中定期观测的关键测试参数包括：溶出介质的温度和体积，转速(第1法和第2法)，浸没

47、频率(第3法)和溶出介质流速(第4法)。Determinetheacceptableperformanceofthedissolutiontestassemblyperiodically.*ThesuitabilityfortheindividualapparatusisdemonstratedbythePerformanceverificationtest.定期检测溶出度测试设备的性能。*单个设备的适用性由性能验证测试给出。Performanceverificationtest,Apparatus1andApparatus2:TestUSPPrednisoneTabletsRSaccordi

48、ngtotheoperatingconditionsspecified.Theapparatusissuitable讦theresultsobtainedarewithintheacceptablerangestatedinthetechnicaldatasheetspecifictothelotusedandtheapparatustested.性能验证测试，第1法和第2法：根据规定的操作条件测试USP强的松片RS。如果结果在技术数据表上该批次和所用仪器的的可接受范围内，则设备是适用的。Performanceverificationtest,Apparatus3:Tocome.性能验证测试，

49、第3法待续Performanceverificationtest,Apparatus4:Tocome.十性能验证测试，第4法待续,PROCEDURE测试方法Apparatus1andApparatus2第1法和第2法IMMEDIATE-RELEASEDOSAGEFORMS速释制剂PlacethestatedvolumeoftheDissolutionmedium(1%)inthevesselofthespecifiedapparatus+givenintheindividualmonograph+,assembletheapparatus,equilibratetheDissolutionme

50、diumto370.5,andremovethethermometer.Place1dosageunitintheapparatus,takingcaretoexcludeairbubblesfromthesurfaceofthedosageunit,andimmediatelyoperatetheapparatusatthespecifiedrate*givenintheindividualmonograph+.Withinthetimeintervalspecified,orateachofthetimesstated,withdrawaspecimenfromazonemidwaybet

51、weenthesurfaceoftheDissolutionmediumandthetopoftherotatingbasketorblade,NLT1cmfromthevesselwall.NoteWheremultiplesamplingtimesarespecified,replacethealiquotswithdrawnforanalysiswithequalvolumesoffreshDissolutionmediumat37or,whereitcanbeshownthatreplacementofthemediumisnotnecessary,correctforthevolum

52、echangeinthecalculation.Keepthevesselcoveredforthedurationofthetest,andverifythetemperatureofthemixtureundertestatsuitabletimes.Performtheanalysis*asdirectedintheindividualmonograph*usingasuitableassaymethod.3Repeatthetestwithadditionaldosageformunits.将各论中给出的溶出介质量（1%）加入到*规定的*容器中，组装好设备，平衡溶出介质温度在370.5

53、C，移出温度计。将1单位剂量的药品小心加入设备中，注意避免表面产生气泡。立即按照*各论中规定的*速率开动设备。在规定的时间间隔或给定的时间点，从溶出介质液面以下和溶出篮或桨叶顶端之间，离杯壁至少1cm的区域取出一份试样。注：如果规定有多次取样，以等体积的37C溶出介质补偿所取液体。或者，如果有证明不需要补偿介质，在计算中修正溶液体积的变化。在检测中保持容器加盖，并以适当的频率验证溶液的温度。按照*各论中规定的*合适的方法进行分析3。重复试验以测试更多的剂量单元。Ifautomatedequipmentisusedforsamplingortheapparatusisotherwisemodif

54、ied,verificationthatthemodifiedapparatuswillproduceresultsequivalenttothoseobtainedwiththestandardapparatusdescribedinthisgeneralchapterisnecessary.如果使用自动化装置取样或者设备在其他方面做出了更改，需要进行验证以显示修改后的设备可以给出与通用章节中的标准设备等效的结果。Dissolutionmedium:Asuitabledissolutionmediumisused.Usethesolventspecified+intheindividualm

55、onograph*.Thevolumespecifiedreferstomeasurementsmadebetween20and25.IftheDissolutionmediumisabufferedsolution,adjustthesolutionsothatitspHiswithin0.05unitofthespecifiedpHgivenintheindividualmonograph*.NoteDissolvedgasescancausebubblestoform,whichmaychangetheresultsofthetest.Ifdissolvedgasesinfluencet

56、hedissolutionresults,dissolvedgasesshouldberemovedbeforetesting.4溶出介质：使用合适的溶出介质。使用*各论中*规定的溶剂。所规定的体积指在20和25C之间所测的值。如果溶出介质是缓冲液，调整缓冲液以保证缓冲液的pH值在*各论中*规定的pH值的0.05以内。注：溶解的气体可以导致气泡的生成，从而改变测试结果。如果溶解的气体会影响溶出结果，在测试前除去溶解的气体4。Time:Whereasingletimespecificationisgiven,thetestmaybeconcludedinashorterperiod讦thereq

57、uirementfortheminimumamountdissolvedismet.Specimensaretobewithdrawnonlyatthestatedtimes,withinatoleranceof2%.时间：当规定了单一的时间时，如果最小溶出量已达到，测试可以提前结束。试样必须在所述时间的2%范围内取出。+Procedureforapooledsampleforimmediate-releasedosageforms:UsethisprocedurewhereProcedureforaPooledSampleisspecifiedintheindividualmonograph

58、.ProceedasdirectedforImmediate-ReleaseDosageFormsinApparatus1andApparatus2intheProceduresection.Combineequalvolumesofthefilteredsolutionsofthesixortwelveindividualspecimenswithdrawn,andusethepooledsampleasthetestspecimen.Determinetheaverageamountoftheactiveingredientdissolvedinthepooledsample.+速释制剂集

59、合样品测试方法：如果各论中有规定测试集合样品，使用本方法。按照测试方法章节中速释制剂第1法和第2法进行。集中全部所测的6或12个单独物种的等体积的溶剂，过滤，使用集合样品作为被测物种，测定集合样品中各活性成分的平均溶出量。EXTENDED-RELEASEDOSAGEFORMS缓释制剂ProceedasdirectedforImmediate-ReleaseDosageForms.按照速释制剂的方法进行。Dissolutionmedium:ProceedasdirectedforImmediate-ReleaseDosageForms.溶出介质：按照立即释放制剂的方法进行。Time:Thetes

60、t-timepoints,generallythree,areexpressedinhours.时间：测试时间点，通常是3个，以小时为单位。DELAYED-RELEASEDOSAGEFORMSNOTACCEPTEDBYTHEJAPANESEPHARMACOPOEIA日本药典未收录的迟释制剂UseMethodAorMethodBandtheapparatusspecified+intheindividualmonograph*.Alltesttimesstatedaretobeobservedwithinatoleranceof%,unlessotherwisespecified.按照各论中的规