溶出度检查法美国药典USP-711

溶出度检查法美国药典USP-7115/20<711>DISSOLUTION溶出度(USP39-NF34Page540)Generalchapter

Dissolution

<711>

isbeingharmonizedwiththecorrespondingtextsofthe

EuropeanPharmacopoeia

and/orthe

JapanesePharmacopoeia.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。Portionsofthepresentgeneralchaptertextthatarenational

USP

text,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.Inthisgeneralchapter,adosageunitisdefinedas1tabletor1capsuleortheamountspecified.

Ofthetypesofapparatusdesignsdescribedherein,usetheonespecifiedintheindividualmonograph.Wherethelabelstatesthatanarticleisentericcoatedandadissolutionordisintegrationtestdoesnotspecificallystatethatitistobeappliedto

delayed-release

articlesandisincludedintheindividualmonograph,theprocedureandinterpretationgivenfor

Delayed-ReleaseDosageForms

areapplied,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Ifthedosageformcontaininggelatindoesnotmeetthecriteriaintheappropriate

AcceptanceTable

(see

Interpretation,

Immediate-ReleaseDosageForms,

Extended-ReleaseDosageForms,or

Delayed-ReleaseDosageForms)becauseofevidenceofthepresenceofcross-linking,thedissolutionprocedureshouldberepeatedwiththeadditionofenzymestothemedium,asdescribedbelow,andthedissolutionresultsshouldbeevaluatedstartingatthefirststageoftheappropriate

AcceptanceTable.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。Gelatin,inthepresenceofcertaincompoundsand/orincertainstorageconditions,includingbutnotrestrictedtohighhumidityandtemperature,maypresentcross-linking.Apelliclemayformontheexternaland/orinternalsurfaceofthegelatincapsuleshelloronthedosageformthatpreventsthedrugfrombeingreleasedduringdissolutiontesting(seemoreinformationin

Capsules—DissolutionTestingandRelatedQualityAttributes

<1094>).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

—

Allreferencestoachapterabove

<1000>

areforinformationpurposesonly,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,activitydeterminedbytheprocedurein

purifiedpepsin,inthe

ReagentSpecifications

section

Shaftandbasketcomponentsofthestirringelementarefabricatedofstainlesssteel,type316,orotherinertmaterial,tothespecificationsshownin

Figure1.Abaskethavingagoldcoatingofabout0.0001inch(2.5µm)thickmaybeused.Adosageunitisplacedinadrybasketatthebeginningofeachtest.Thedistancebetweentheinsidebottomofthevesselandthebottomofthebasketismaintainedat25±2mmduringthetest.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（2.5μm）的篮筐。开始检测时，将一剂药品至于干燥的篮筐中。在测试过程中，溶出杯底部到篮筐底部的距离应保持在25±2mm。Figure1.Basketstirringelement.图1.转篮组成Apparatus2(PaddleApparatus)第2法（桨法）Usetheassemblyfrom

Apparatus1,exceptthatapaddleformedfromabladeandashaftisusedasthestirringelement.TheshaftispositionedsothatitsaxisisNMT2mmfromtheverticalaxisofthevesselatanypointandrotatessmoothlywithoutsignificantwobblethatcouldaffecttheresults.Theverticalcenterlineofthebladepassesthroughtheaxisoftheshaftsothatthebottomofthebladeisflushwiththebottomoftheshaft.Thepaddleconformstothespecificationsshownin

Figure2.Thedistanceof25±2mmbetweenthebottomofthebladeandtheinsidebottomofthevesselismaintainedduringthetest.Themetallicorsuitablyinert,rigidbladeandshaftcomposeasingleentity.Asuitabletwo-part,detachabledesignmaybeused,providedthattheassemblyremainsfirmlyengagedduringthetest.Thepaddlebladeandshaftmaybecoatedwithasuitablecoatingsoastomakebothoftheminert.Thedosageunitisallowedtosinktothebottomofthevesselbeforerotationofthebladeisstarted.Asmall,loosepieceofnonreactivematerial,suchasNMTafewturnsofwirehelix,maybeattachedtodosageunitsthatwouldotherwisefloat.Analternativesinkerdeviceisshownin

Figure2a.Othervalidatedsinkerdevicesmaybeused.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25±2mm。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。其他经验证的沉子也可以使用。Figure2.Paddlestirringelement.图2.搅拌桨组成Figure2a.Alternativesinker.Alldimensionsareexpressedinmm.图2a.可选的沉降篮（单位均为mm）Apparatus3(ReciprocatingCylinder)第3法（往复圆筒法）notacceptedbythejapanesepharmacopoeia日本药典未收录Theassemblyconsistsofasetofcylindrical,flat-bottomedglassvessels;asetofglassreciprocatingcylinders;inertfittings(stainlesssteeltype316orothersuitablematerial),andscreensthataremadeofsuitablenonsorbingandnonreactivematerialandthataredesignedtofitthetopsandbottomsofthereciprocatingcylinders;andamotoranddriveassemblytoreciprocatethecylindersverticallyinsidethevessels;ifdesired,indexthereciprocatingcylindershorizontallytoadifferentrowofvessels.Thevesselsarepartiallyimmersedinasuitablewaterbathofanyconvenientsizethatpermitsholdingthetemperatureat37±0.5°duringthetest.Nopartoftheassembly,includingtheenvironmentinwhichtheassemblyisplaced,contributessignificantmotion,agitation,orvibrationbeyondthatduetothesmooth,verticallyreciprocatingcylinder.Adeviceisusedthatallowsthereciprocationratetobeselectedandmaintainedatthespecifieddiprate

givenintheindividualmonograph

within±5%.Anapparatusthatpermitsobservationofthespecimensandreciprocatingcylindersispreferable.Thevesselsareprovidedwithevaporationcapsthatremaininplaceforthedurationofthetest.Thecomponentsconformtothedimensionsshownin

Figure3,unlessotherwisespecified

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37±0.5℃。仪器的任何部件，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，各部分的尺寸如图3所示。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）Theassemblyconsistsofareservoirandapumpforthe

Dissolutionmedium;aflow-throughcell;andawaterbaththatmaintainstheDissolutionmedium

at37±0.5°.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37±0.5℃。使用各论中规定的尺寸。Thepumpforcesthe

Dissolutionmedium

upwardthroughtheflow-throughcell.Thepumphasadeliveryrangebetween240and960mL/h,withstandardflowratesof4,8,and16mL/min.Itmustdeliveraconstantflow(±5%ofthenominalflowrate);theflowprofileissinusoidalwithapulsationof120±10pulses/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，标准速率为4，8，16mL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120±10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(see

Figure4

and

Figure5),oftransparentandinertmaterial,ismountedverticallywithafiltersystem(specifiedintheindividualmonograph)thatpreventsescapeofundissolvedparticlesfromthetopofthecell;standardcelldiametersare12and22.6mm;thebottomconeisusuallyfilledwithsmallglassbeadsofabout1-mmdiameterwithonebeadofabout5mm,positionedattheapextoprotectthefluidentrytube;andatabletholder(see

Figure4

and

Figure5)isavailableforpositioningofspecialdosageforms,e.g.,inlaytablets.Thecellisimmersedinawaterbath,andthetemperatureismaintainedat37±0.5°.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37±0.5℃的水浴中。Figure4.Apparatus4:largecellfortabletsandcapsules(top);tabletholderforthelargecell(bottom).(Allmeasurementsareexpressedinmmunlessnotedotherwise.)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。）Figure5.Apparatus4:smallcellfortabletsandcapsules(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-ringstoassemblethecell.Thepumpisseparatedfromthedissolutionunittoshieldthelatteragainstanyvibrationsoriginatingfromthepump.Thepositionofthepumpshouldnotbeonalevelhigherthanthereservoirflasks.Tubeconnectionsareasshortaspossible.Usesuitablyinerttubing,suchaspolytef,withabouta1.6-mminnerdiameterandchemicallyinert,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.Inaddition,criticaltestparametersthathavetobemonitoredperiodicallyduringuseincludevolumeandtemperatureofthe

Dissolutionmedium,rotationspeed(Apparatus1

and

Apparatus2),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），浸没频率（第3法）和溶出介质流速（第4法）。Determinetheacceptableperformanceofthedissolutiontestassemblyperiodically.

Thesuitabilityfortheindividualapparatusisdemonstratedbythe

Performanceverificationtest.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:

Test

USPPrednisoneTabletsRS

accordingtotheoperatingconditionsspecified.Theapparatusissuitableiftheresultsobtainedarewithintheacceptablerangestatedinthetechnicaldatasheetspecifictothelotusedandtheapparatustested.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，第3法——[待续]Performanceverificationtest,Apparatus4:

[Tocome.]

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Placethestatedvolumeofthe

Dissolutionmedium

(±1%)inthevesselofthespecifiedapparatus

givenintheindividualmonograph

,assembletheapparatus,equilibratethe

Dissolutionmedium

to37±0.5°,andremovethethermometer.Place1dosageunitintheapparatus,takingcaretoexcludeairbubblesfromthesurfaceofthedosageunit,andimmediatelyoperatetheapparatusatthespecifiedrate

givenintheindividualmonograph

.Withinthetimeintervalspecified,orateachofthetimesstated,withdrawaspecimenfromazonemidwaybetweenthesurfaceofthe

Dissolutionmedium

andthetopoftherotatingbasketorblade,NLT1cmfromthevesselwall.

[Note

—

Wheremultiplesamplingtimesarespecified,replacethealiquotswithdrawnforanalysiswithequalvolumesoffresh

Dissolutionmedium

at37°or,whereitcanbeshownthatreplacementofthemediumisnotnecessary,correctforthevolumechangeinthecalculation.Keepthevesselcoveredforthedurationofthetest,andverifythetemperatureofthemixtureundertestatsuitabletimes.

]

Performtheanalysis

asdirectedintheindividualmonograph

usingasuitableassaymethod.3

Repeatthetestwithadditionaldosageformunits.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37±0.5℃，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37℃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。Ifautomatedequipmentisusedforsamplingortheapparatusisotherwisemodified,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

intheindividualmonograph

.Thevolumespecifiedreferstomeasurementsmadebetween20°and25°.Ifthe

Dissolutionmedium

isabufferedsolution,adjustthesolutionsothatitspHiswithin0.05unitofthespecifiedpH

givenintheindividualmonograph

.

[

Note

—

Dissolvedgasescancausebubblestoform,whichmaychangetheresultsofthetest.Ifdissolvedgasesinfluencethedissolutionresults,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25℃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,thetestmaybeconcludedinashorterperiodiftherequirementfortheminimumamountdissolvedismet.Specimensaretobewithdrawnonlyatthestatedtimes,withinatoleranceof±2%.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:

Usethisprocedurewhere

ProcedureforaPooledSample

isspecifiedintheindividualmonograph.Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2

intheProcedure

section.Combineequalvolumesofthefilteredsolutionsofthesixortwelveindividualspecimenswithdrawn,andusethepooledsampleasthetestspecimen.Determinetheaverageamountoftheactiveingredientdissolvedinthepooledsample.

速释制剂集合样品测试方法：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Proceedasdirectedfor

Immediate-ReleaseDosageForms.按照速释制剂的方法进行。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms.溶出介质：按照立即释放制剂的方法进行。Time:

Thetest-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Use

MethodA

or

MethodB

andtheapparatusspecified

intheindividualmonograph

.Alltesttimesstatedaretobeobservedwithinatoleranceof±2%,unlessotherwisespecified.按照各论中的规定，使用方法A或方法B。除另有规定外，所有测试时间与规定相差不得过±2%。MethodAProcedure

(unlessotherwisedirected

intheindividualmonograph)

方法A程序（除各论中另有规定外）acidstage酸阶段Place750mLof0.1Nhydrochloricacidinthevessel,andassembletheapparatus.Allowthemediumtoequilibratetoatemperatureof37±0.5°.Place1dosageunitintheapparatus,coverthevessel,andoperatetheapparatusatthespecifiedrate

giveninthemonograph

.向容器中加入0.1N的盐酸750mL，组装设备。将介质平衡在37±0.5℃。将1单位剂量的药品加入设备中，盖上容器，依照各论中规定的速率启动设备。After2hofoperationin0.1Nhydrochloricacid,withdrawanaliquotofthefluid,andproceedimmediatelyasdirectedinthe

BufferStage.在0.1N的盐酸中搅拌2小时后，吸取一份试样溶液，然后立即按照缓冲液阶段的说明继续操作。Performananalysisofthealiquotusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.

以适合的方法测试试样。测试方法在各论中给出。bufferstage缓冲液阶段[

Note

—

CompletetheoperationsofaddingthebufferandadjustingthepHwithin5min.

]

Withtheapparatusoperatingattheratespecified

inthemonograph

,addtothefluidinthevessel250mLof0.20Mtribasicsodiumphosphatethathasbeenequilibratedto37±0.5°.Adjust,ifnecessary,with2Nhydrochloricacidor2NsodiumhydroxidetoapHof6.8±0.05.Continuetooperatetheapparatusfor45min,orforthespecifiedtime

givenintheindividualmonograph

.Attheendofthetimeperiod,withdrawanaliquotofthefluid,andperformtheanalysisusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.Thetestmaybeconcludedinashortertimeperiodthanthatspecifiedforthe

BufferStage

iftherequirementfortheminimumamountdissolvedismetatanearliertime.

[注：加入缓冲液和调节pH的操作应在5分钟内完成。]设备在各论中规定的速率下运行，向容器中加入250mL预先平衡在37±0.5℃的0.20M的磷酸钠。必要时用2N的盐酸或2N的氢氧化钠调节pH至6.8±0.05。继续运转45分钟或各论中给定的时间。到时间后，吸取一份试样溶液，以适合的方法测试。测试方法在各论中给出。如果缓冲液阶段的最小溶出量已提前达到，测试可以提前结束。MethodBProcedure

(unlessotherwisedirected

intheindividualmonograph)

方法B程序（除各论中另有规定外）acidstage酸阶段Place1000mLof0.1Nhydrochloricacidinthevessel,andassembletheapparatus.Allowthemediumtoequilibratetoatemperatureof37±0.5°.Place1dosageunitintheapparatus,coverthevessel,andoperatetheapparatusattheratespecified

inthemonograph

.After2hofoperationin0.1Nhydrochloricacid,withdrawanaliquotofthefluid,andproceedimmediatelyasdirectedinthe

BufferStage.向容器中加入0.1N的盐酸1000mL，组装设备。将介质平衡在37±0.5℃。将1单位剂量的药品加入设备中，盖上容器，依照各论中规定的速率启动设备。在0.1N的盐酸中搅拌2小时后，吸取一份试样溶液，然后立即按照缓冲液阶段的说明继续操作。Performananalysisofthealiquotusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.

以适合的方法测试试样。测试方法在各论中给出。bufferstage缓冲液阶段[

Note

—

Forthisstageoftheprocedure,usebufferthatpreviouslyhasbeenequilibratedtoatemperatureof37±0.5°.

]

Draintheacidfromthevessel,andaddtothevessel1000mLofpH6.8phosphatebuffer,preparedbymixing0.1Nhydrochloricacidwith0.20Mtribasicsodiumphosphate(3:1)andadjusting,ifnecessary,with2Nhydrochloricacidor2NsodiumhydroxidetoapHof6.8±0.05.

[Note

—

Thismayalsobeaccomplishedbyremovingfromtheapparatusthevesselcontainingtheacid,thenreplacingitwithanothervesselcontainingthebuffer,andtransferringthedosageunittothevesselcontainingthebuffer.

][注：此阶段使用预先平衡在37±0.5℃的缓冲液。]抽干容器中的酸液，加入1000mLpH6.8的磷酸盐缓冲液（0.1N盐酸加0.20M磷酸钠，3：1）。必要时用2N的盐酸或2N的氢氧化钠调节pH至6.8±0.05。[注：也可以将设备中盛装酸液的容器移出，换以另一盛装缓冲液的容器，将药剂转移到缓冲液容器中。]Continuetooperatetheapparatusfor45min,orforthespecifiedtime

givenintheindividualmonograph

.Attheendofthetimeperiod,withdrawanaliquotofthefluid,andperformtheanalysisusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.Thetestmaybeconcludedinashortertimeperiodthanthatspecifiedforthe

BufferStage

iftherequirementforminimumamountdissolvedismetatanearliertime.

继续运转45分钟或各论中给定的时间。到时间后，吸取一份试样溶液，以适合的方法测试。测试方法在各论中给出。如果缓冲液阶段的最小溶出量已提前达到，测试可以提前结束。Apparatus3(ReciprocatingCylinder)第3法（往复圆筒法）notacceptedbythejapanesepharmacopoeiaimmediate-releasedosageforms日本药典未收录的速释制剂Placethestatedvolumeofthe

Dissolutionmedium

ineachvesseloftheapparatus,assembletheapparatus,equilibratethe

Dissolutionmedium

to37±0.5°,andremovethethermometer.Place1dosageformunitineachofthesixreciprocatingcylinders,takingcaretoexcludeairbubblesfromthesurfaceofeachdosageunit,andimmediatelyoperatetheapparatusasspecified

intheindividualmonograph

.Duringtheupwardanddownwardstrokes,thereciprocatingcylindermovesthroughatotaldistanceof9.9–10.1cm.Withinthetimeintervalspecified,orateachofthetimesstated,raisethereciprocatingcylindersandwithdrawaportionofthesolutionundertestfromazonemidwaybetweenthesurfaceofthe

Dissolutionmedium

andthebottomofeachvessel.Performtheanalysisasdirected

intheindividualmonograph

.Ifnecessary,repeatthetestwithadditionaldosage-formunits.将指定量的溶出介质加入到设备的每个容器中，组装好设备，平衡溶出介质温度在37±0.5℃，移出温度计。在6个往复圆筒中分别加入1单位剂量的药品，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。在上行和下行冲程中，往复圆筒移动的总距离为9.9到10.1cm。在规定的时间间隔或者每个给定的时间点，抬起往复圆筒，从溶出介质的表面到容器底部的中点区域取出一部分测试溶液。按照各论中的规定测试。必要时重复测试更多份的样品。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.溶出介质：同第1法和第2法下立即释放制剂项下处理。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.时间：同第1法和第2法下立即释放制剂项下处理。extended-releasedosageforms缓释制剂Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus3.同第3法下速释制剂项下处理。Dissolutionmedium:

Proceedasdirectedfor

Extended-ReleaseDosageForms

in

Apparatus1andApparatus2.溶出介质：同第1法和第2法下缓释制剂项下处理。Time:

Proceedasdirectedfor

Extended-ReleaseDosageForms

in

Apparatus1andApparatus2.时间：同第1法和第2法下缓释制剂项下处理。delayed-releasedosageforms迟释制剂Proceedasdirectedfor

Delayed-ReleaseDosageForms,MethodB

in

Apparatus1andApparatus2,usingonerowofvesselsfortheacidstagemediaandthefollowingrowofvesselsforthebufferstagemedia,andusingthevolumeofmediumspecified(usually300mL).同第1法和第2法下迟释制剂方法B项下处理。酸性阶段使用一排容器，缓冲液阶段使用另一排容器。使用规定体积的介质（通常为300mL）。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.时间：同第1法和第2法下立即释放制剂项下处理。Apparatus4(Flow-ThroughCell)第4法（流通池法）immediate-releasedosageforms速释制剂Placetheglassbeadsintothecellspecified

inthemonograph

.Place1dosageunitontopofthebeadsor,ifspecified

inthemonograph

,onawirecarrier.Assemblethefilterhead,andfixthepartstogetherbymeansofasuitableclampingdevice.Introducebythepumpthe

Dissolutionmedium

warmedto37±0.5°throughthebottomofthecelltoobtaintheflowratespecified

intheindividualmonograph

andmeasuredwithanaccuracyof5%.Collecttheeluatebyfractionsateachofthetimesstated.Performtheanalysisasdirected

intheindividualmonograph

.Repeatthetestwithadditionaldosageformunits.依照规定将玻璃珠装入流通池。将1单位剂量的药品置于玻璃珠上。如果各论中另有规定，也可置于载具上。装上过滤头，用合适的夹子夹紧。平衡在37±0.5℃的溶出介质被泵由下而上泵入流通池，流速按各论中的规定，精确到5%。在每个给定的时间点收集浸出液。按照各论中的规定进行分析。重复试验以测试更多的剂量单元。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.溶出介质：同第1法和第2法下立即释放制剂项下处理。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.时间：同第1法和第2法下立即释放制剂项下处理。extended-releasedosageforms缓释制剂Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus4.同第4法立即释放制剂项下处理。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus4.溶出介质：同第4法下立即释放制剂项下处理。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus4.时间：同第4法下立即释放制剂项下处理。delayed-releasedosageforms迟释制剂Proceedasdirectedfor

Delayed-ReleaseDosageForms

in

Apparatus1andApparatus2,usingthespecifiedmedia.同第1法和第2法下迟释制剂项下处理。Time:

Proceedasdirectedfor

Delayed-ReleaseDosageForms

in

Apparatus1andApparatus2.时间：同第1法和第2法下迟释制剂项下处理。

INTERPRETATION判断Immediate-ReleaseDosageForms速释制剂Unlessotherwisespecified

intheindividualmonograph

,therequirementsaremetifthequantitiesofactiveingredientdissolvedfromthedosageunitstestedconformto

AcceptanceTable1.Continuetestingthroughthethreestagesunlesstheresultsconformateither

S1

or

S2

.Thequantity,

Q,istheamountofdissolvedactiveingredient

specifiedintheindividualmonograph

,expressedasapercentageofthelabeledcontentofthedosageunit;the5%,15%,and25%valuesin

AcceptanceTable1

arepercentagesofthelabeledcontentsothatthesevaluesand

Q

areinthesameterms.除各论中另有规定外，如果制剂单位中溶出的活性成分的量达到接受限度表1中的规定，认为合格。连续测试3个阶段，除非结果符合S1或S2的限度。溶出量Q指各论中规定的活性成分溶出的量，以标示量的百分比表示。限度表1中的5%，15%和25%是指标示量的百分比，和Q相同。AcceptanceTable1接受限度表1Stage阶段NumberTested样品数量AcceptanceCriteria接受限度S16EachunitisNLT

Q+5%.每个单位不少于Q+5%.S26Averageof12units(S1+S2)is≥

Q,

andnounitis<Q-15%.12单位(S1+S2)的平均值大于等于Q，且任意一单位不少于Q-15%.S312Averageof24units(S1+S2+S3)is≥

Q,NMT2unitsare<Q

-15%,andnounitis<Q-25%.24单位(S1+S2+S3)的平均值大于等于Q，其中最多2单位少于Q-15%，没有任一单位少于Q-25%.

Immediate-ReleaseDosageFormsPooledSample立即释放制剂集合样品Unlessotherwisespecifiedintheindividualmonograph,therequirementsaremetifthequantitiesofactiveingredientdissolvedfromthepooledsampleconformtotheaccompanying

AcceptanceTableforaPooledSample

.Continuetestingthroughthethreestagesunlesstheresultsconformateither

S

1

or

S

2

.Thequantity,

Q,istheamountofdissolvedactiveingredientspecifiedintheindividualmonograph,expressedasapercentageofthelabeledcontent.除各论中另有规定外，如果集合样品中溶出的活性成分的量达到随附的集合样品接受限度表中的规定，认为合格。连续测试3个阶段，除非结果符合S1或S2的限度。溶出量Q指各论中规定的活性成分溶出的量，以标示量的百分比表示。AcceptanceTableforaPooledSample集合样品接受限度表Stage阶段NumberTested样品数量AcceptanceCriteria接受限度S16AverageamountdissolvedisNLT

Q+10%.平均溶出量不少于Q+10%.S26Averageamountdissolved(S1+S2)is≥

Q+5%.平均溶出量(S1+S2)大于等于Q+5%。S312Averageamountdissolved(S1+S2+S3)is≥

Q.平均溶出量(S1+S2+S3)大于等于Q。Extended-ReleaseDosageForms缓释制剂Unlessotherwisespecified

intheindividualmonograph

,therequirementsaremetifthequantitiesofactiveingredientdissolvedfromthedosageunitstestedconformto

AcceptanceTable2.Continuetestingthroughthethreelevelsunlesstheresultsconformateither

L

1

or

L

2.Limitsontheamountsofactiveingredientdissolvedareexpressedintermsofthepercentageoflabeledcontent.Thelimitsembraceeachvalueof

Qi,theamountdissolvedateachspecifiedfractionaldosinginterval.Wheremorethanonerangeisspecified

intheindividualmonograph

,theacceptancecriteriaapplyindividuallytoeachrange.除各论中另有规定外，如果制剂单位中溶出的活性成分的量达到接受限度表2中的规定，认为合格。连续测试3个等级，除非结果符合L1或L2的限度。活性成分溶出量的限度以标示量的百分比的形式给出。限度包含每个规定给药间隔所测得的溶出量Qi。如果各论中规定了不止一个范围，接受限度适用于每个范围。AcceptanceTable2接受限度表2Level等级Number

Tested样品数量Criteria限度L16Noindividualvalueliesoutsideeachofthestatedranges,andnoindividualvalueislessthanthestatedamountatthefinaltesttime.每个规定的范围均无测量值超出限度，测试结束时没有任何测量值小于规定溶出量。L26Theaveragevalueofthe12units(L1+L2)lieswithineachofthestatedrangesandisNLTthestatedamountatthefinaltesttime;noneis>10%oflabeledcontentoutsideeachofthestatedranges;andnoneis>10%ofthelabeledcontentbelowthestatedamountatthefinaltesttime.12个单元(L1+L2