溶出度檢查法美國藥典USP-711

1、DISSOLUTION溶出度(USP39-NF34Page540)GeneralchapterDissolutionv711isbeingharmonizedwiththecorrespondingtextsoftheEuropeanPharmacopoeiaand/ortheJapanesePharmacopoeia.Thesepharmacopeiashaveundertakentonotmakeanyunilateralchangetothisharmonizedchapter.通則溶出度與歐盟藥典和日本藥典中的相應部分相統(tǒng)一。這三部藥典承諾不做單方面的修改。Portionsofthep

2、resentgeneralchaptertextthatarenationalUSPtext,andthereforenotpartoftheharmonizedtext,aremarkedwithsymbolstospecifythisfact.本章中的部分文字為本國USP內(nèi)容，并沒有與其他藥典統(tǒng)一。此部分以(*)標注。Thistestisprovidedtodeterminecompliancewiththedissolutionrequirements+wherestatedintheindividualmonograph*fordosageformsadministeredorally

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

4、ayed-releasearticlesandisincludedintheindividualmonograph,theprocedureandinterpretationgivenforDelayed-ReleaseDosageFormsareapplied,unlessotherwisespecifiedintheindividualmonograph.本測試用于檢測藥品口服制劑的溶出度是否符合*各論*中的規(guī)定。本章中，除另有規(guī)定外，單位制劑定義為1片或1粒膠囊。*對于本章中所述多種儀器，使用各論中規(guī)定的種類。除各論中另有規(guī)定外，如果檢品是腸溶衣片且各論中的溶出度或崩解時限檢查項下沒有特

5、別指出適用遲釋劑的，使用本章中適用于遲釋劑的流程和解釋。FORDOSAGEFORMSCONTAININGORCOATEDWITHGELATIN涂有或包含明膠的劑型IfthedosageformcontaininggelatindoesnotmeetthecriteriaintheappropriateAcceptanceTable(seeInterpretation,Immediate-ReleaseDosageForms,Extended-ReleaseDosageForms,orDelayed-ReleaseDosageForms)becauseofevidenceofthepresenc

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

7、firststagetesting,andevidenceofcross-linkingisobserved.如果劑型中含有明膠，其不符合驗收表中的標準(見判斷，速釋制劑，延釋制劑，緩釋制劑，因為存在明膠交聯(lián)結(jié)合作用，它的溶解過程與外加的媒介酶是重復的，見下面的描述，并且溶解結(jié)果可以通過適當?shù)尿炇毡淼拈_始的第一階段標準進行評估。如果溶出結(jié)果不滿足第一階段的測試標準，那么就沒有必要繼續(xù)測試到最后階段，并且也證明了明膠交聯(lián)結(jié)合作用的存在。Gelatin,inthepresenceofcertaincompoundsand/orincertainstorageconditions,including

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

9、.明膠，存在于某一處方和/或某一儲存條件下，如：高溫高濕，可能存在明膠交聯(lián)結(jié)合作用。在膠囊殼或其他劑型的外表面和/或內(nèi)表面形成一層膜阻止溶出試驗過程中藥物的釋放(見膠囊-溶出度檢測和相關(guān)質(zhì)量屬性)。NoteAllreferencestoachapteraboveareforinformationpurposesonly,foruseasahelpfulresource.Thesechaptersarenotmandatoryunlessexplicitlycalledoutforthisapplication.注-超過章節(jié)的所有引用應用的目的僅為提供參考信息。這些章節(jié)是非強制的，除非另有規(guī)定。

10、DissolutionMediumwithpH4.0pH4.0and4.0和6.8pH6.8的溶出介質(zhì)Enzyme:Pancreatin,proteaseactivitydeterminedbytheprocedureinAssayforproteaseactivity(Caseindigestivepower)inthemonographforPancreatin酶：胰液素，蛋白酶活性視胰液素專論中的蛋白酶活性(酪蛋白消化能力)分析中的生產(chǎn)過程而定。Amount:AquantityofpancreatinthatresultsinaproteaseactivityofNMT2000Units

11、/Lofdissolutionmedium數(shù)量：一些胰液素對溶出介質(zhì)提供NMT550,000單位/L的蛋白酶活性。DissolutionMediumContainingSurfactantorOtherIngredientsKnowntoDenaturetheEnzyme含有表面活性劑或其他已知成分變性酶的溶出介質(zhì)Ifthedissolutionmediumcontainssurfactantorotheringredientsthatareknowntodenaturetheenzymeused,apretreatmentstepinthedissolutiontestingofthedos

12、ageformmaybeapplied.ThispretreatmentstepisdoneusingthespecifieddissolutionmediumwithoutthesurfactantortheingredientandwiththeadditionoftheappropriateamountofenzymeaccordingtothemediumpH.Theamountofenzymeaddedisappropriatetothevolumeofdissolutionmediumusedinthepretreatment.Toachievethespecifiedmedium

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

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

15、ontinuefor30minaftertheadditionoftheingredient.如果溶出介質(zhì)中添加了表面活性劑或其他已知成分的變性酶，那么此溶出實驗就要把預處理步驟考慮進去。預處理過程就是是根據(jù)溶出介質(zhì)的pH來確定加入酶的量，此處的溶出介質(zhì)不含有表面活性劑和原料。酶加入的量要適合預處理所用的溶出介質(zhì)的體積。為了達到最終溶出試驗所需要的特定的溶出介質(zhì)的體積，預處理階段所用的溶出介質(zhì)（不含原料）的體積要稍微小點，如此在預處理最后階段加入原料的時候方可獲得最終的溶出介質(zhì)體積。其他所有的測試條件（如：設備、轉(zhuǎn)速、流速）應該與方法或?qū)Ｕ撝忻枋龅囊恢?。通常預處理階段的持續(xù)時間為NMT15mi

16、n。所需的預處理時間應該根據(jù)具體案例具體分析，且應該科學、合理。預處理時間應該包含在實驗的總時間里。例如，如果實驗的總時間為45min,預處理時間為15min，那么加入原料后實驗還要繼續(xù)進行30min。USPReferenceStandards11一USPPrednisoneTablets.RSUSP參考標準-USP強的松片RS。APPARATUS儀器Apparatus1（BasketApparatus）第1法（籃法）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%.設備由下列部分組成：有蓋或無蓋的溶出杯，由玻璃或其他惰性的透明材料1制成；馬達；轉(zhuǎn)軸；轉(zhuǎn)籃。溶出杯部分浸沒在合適大小的水浴中，或者由合適的裝置加熱，例如電熱套。水浴或加熱裝置需能在測試過程中將杯內(nèi)溫度保持在370.5C，并且容許杯內(nèi)液體持續(xù)、平緩的流動。整個儀器包括周圍的環(huán)境，除了平穩(wěn)轉(zhuǎn)動的攪拌部件，不得有明顯的運動，攪動或振動。儀器最好能允許在檢測過程中能夠觀察到檢品和攪拌部件。溶出杯為圓柱形，底部為半球形，尺寸和容積如下：名義容積1L的，高160210

22、mm，內(nèi)徑98106mm；名義容積2L的，高280300mm，內(nèi)徑98106mm；名義容積4L的，高280300mm，內(nèi)徑145155mm。內(nèi)壁頂部有緣。可以使用合適的蓋子減緩溶劑蒸發(fā)2。轉(zhuǎn)軸與溶出杯的縱軸在任意部位不得相差差過2mm,轉(zhuǎn)動平滑，無明顯搖晃以至于影響檢測結(jié)果。速度調(diào)節(jié)裝置控制轉(zhuǎn)軸的轉(zhuǎn)速，并可維持*在各論中規(guī)定值*的4%范圍內(nèi)。Shaftandbasketcomponentsofthestirringelementarefabricatedofstainlesssteel,type316,orotherinertmaterial,tothespecificationsshowni

23、nFigure1.Abaskethavingagoldcoatingofabout0.0001inch(2.5pm)thickmaybeused.Adosageunitisplacedinadrybasketatthebeginningofeachtest.Thedistancebetweentheinsidebottomofthevesselandthebottomofthebasketismaintainedat252mmduringthetest.轉(zhuǎn)軸和籃筐組件由316號不銹鋼或者其他惰性材料制成，尺寸如圖1所示?？墒褂缅兘鸷穸?.0001英寸(2.5pm)的籃筐。開始檢測時，將一劑藥品

24、至于干燥的籃筐中。在測試過程中，溶出杯底部到籃筐底部的距離應保持在252mm。ClearopeningVenthole2.0+0.5mmdiameterFigure1.Basketstirringelement.圖1.ClearopeningVenthole2.0+0.5mmdiameterFigure1.Basketstirringelement.圖1.轉(zhuǎn)籃組成Apparatus2（PaddleApparatus第2法（槳法）Retentionspringwith3langson120centersScreenO.D.22.21.0mmScreenwithweldedseam：0,27-0,

25、31mmwiredhnneterwithwiretip輕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法中的設備，除了使用一個由葉片和轉(zhuǎn)軸組成的槳作為攪拌單元。轉(zhuǎn)軸與溶出杯的縱軸在任意部位不得相差差過2mm,轉(zhuǎn)動平滑，無明顯搖晃以至于影響檢測結(jié)果。葉片的垂直中性線穿過轉(zhuǎn)軸的軸線，葉片的下緣與轉(zhuǎn)軸底部平齊。槳的尺寸應符合圖2中的規(guī)定。在測試過程中，葉片底部與溶出杯底部的距離應保持在252mm。金屬或硬質(zhì)的葉片和轉(zhuǎn)軸應是一個整體。兩部分組合的設計也可以使用，只要組件在檢測過程中牢固固定在一起?？梢栽跇~和轉(zhuǎn)軸上涂布合適的涂層以使其為惰性。在槳葉開始旋轉(zhuǎn)前，將一劑藥品沉至溶出杯底。如果藥劑浮在頁面上，可以在其上附著一個惰性，松弛的小部件，例如幾圈線圈，使其沉沒。圖2是一種可替代使用的沉子。其

30、他經(jīng)驗證的沉子也可以使用。NotesAandBdimensionsarenottovarymorethan0.5mmwhenpartisrdtatAdnncenterlineaxis.TolerancesareNotesAandBdimensionsarenottovarymorethan0.5mmwhenpartisrdtatAdnncenterlineaxis.Tolerancesare1.0mmunlessotherwisestated.4.0Il.0mmFigure2.Paddlestirringelement.圖2.攪拌槳組成3,5-4,0.5-4.0A;Acid-resistant

31、wirecla?pB;ftcid-resistantwiresupportFigure2a.Alternativesinker.Alldimensionsareexpressedinmm.圖2a.可選的沉降籃(單位均為mm)Apparatus3(ReciprocatingCylinder)3法(往復圓筒法)NOTACCEPTEDBYTHEJAPANESEPHARMACOPOEIA日本藥典未收錄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*.所用設備包含一套圓柱形平底玻璃杯；一套玻璃往復圓筒；惰性配件(316號不銹鋼或其他合適的材質(zhì))；由合適的非吸附，不反應材料制成的篩網(wǎng)，擋在往復圓筒的上下兩端；一套馬達和傳動裝置，將圓筒在玻璃杯中垂直往復運動，如果需要，也可以將往復圓筒平行移至另一行玻璃杯中。玻璃杯部分浸沒在合適尺寸的水浴中，水浴溫度保持在370.5Co儀器的任

36、何部件，以及儀器所處的環(huán)境，都不應當引起明顯的移動，攪動，振動，除了平滑的垂直往復運動的圓筒。使用設備維持往復速度*在各論中所規(guī)定*值的5%范圍內(nèi)。儀器最好可以在檢測過程中觀察到樣品和往復圓筒。玻璃杯配有蒸發(fā)帽，在檢測中一直蓋在玻璃杯上。除另有規(guī)定外辛，各部分的尺寸如圖3所示。50,S-|1Airholes3,90.1diameterEvaporationcapIii38.116-8diameterType316stainlesssteelAirholes3.90.1diameterMeshscreen50,S-|1Airholes3,90.1diameterEvaporationcapIii

37、38.116-8diameterType316stainlesssteelAirholes3.90.1diameterMeshscreenAGlassreciprocatingcylinderMeshscreen471.4+i噸一Gia$Figure3.Apparatus3（reciprocatingcylinder）.圖3.圖3第3法（往復圓筒法）設備Apparatus4（Flow-ThroughCell第4法（流通池法）TheassemblyconsistsofareservoirandapumpfortheDissolutionmedium;aflowthroughcell;andawa

38、terbaththatmaintainstheDissolutionmediumat370.5.Usethespecifiedcellsize+asgivenintheindividualmonograph*.所用設備包含一個溶出介質(zhì)的容器和相應的泵，一個流通池和水浴。水浴將溶出介質(zhì)保持在370.5C。使用*各論中規(guī)定*的尺寸。ThepumpforcestheDissolutionmediumupwardthroughtheflow-throughcell.Thepumphasadeliveryrangebetween240and960mL/h,withstandardflowratesof4

39、,8,and16mL/min.Itmustdeliveraconstantflow(土5%ofthenominalflowrate);theflowprofileissinusoidalwithapulsationof12010pulses/min.Apumpwithoutpulsationmayalsobeused.Dissolutiontestproceduresusingaflow-throughcellmustbecharacterizedwithrespecttorateandanypulsation.泵將溶出介質(zhì)推動，向上通過流通池。泵的傳輸能力在240到960mL每小時之間，標準

40、速率為4，&16mL每分鐘。泵的流速必須均勻(名義流量的5%以內(nèi))。泵的流量特性曲線應為正弦波，脈沖為每分鐘12010沖。無脈沖泵也可以使用。使用流通池法的溶出度測試必須對應特定的流速和脈沖。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(見圖4和圖5)垂直安放，配有過濾系統(tǒng)(在各論中規(guī)定)以防止未溶解的顆粒從流通池頂部逸出。標準的流通池直徑為12和22.6mm。底部的錐形通常填有直徑約1mm的小玻璃珠，其中一顆約5mm大的玻璃珠置于頂點處，以保護液體輸入管。流通池配有藥片架(見圖4和圖5)一滿足特殊制劑的需要，如泡騰片。流通池浸沒在370.5C的水浴中。0=diametertabletsandcapsules(top);tabletholderforthelargecell(bottom).(Allmeasurements

43、areexpressedinmmunlessnotedotherwise.)圖4.第4法設備，盛裝片劑和膠囊的大流通池(上)大藥片架(下)(除另有說明，所有尺寸單位為mm。)tabletsandcapsules(top);tabletholderforthesmallcell(bottom).(Allmeasurementsareexpressedinmmunlessnotedotherwise.)圖5第4法設備，盛裝片劑和膠囊的小流通池(上)，小藥片架(下)。(除另有說明，所有尺寸單位為mm。)TheapparatususesaclampmechanismandtwoO-ringstoass

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

45、t,flanged-endconnections.流通池使用一個架子和2個O形圈固定。泵與溶出單元分開，以防止泵的振動干擾到后者。泵的水平位置不得高于溶出介質(zhì)容器。管線連接盡可能短。使用合適的惰性管線，如聚四氟乙烯，內(nèi)徑1.6mm。法蘭連接也應為化學惰性。APPARATUSSUITABILITY設備適用性Thedeterminationofsuitabilityofatestassemblytoperformdissolutiontestingmustincludeconformancetothedimensionsandtolerancesoftheapparatusasgivenabove

46、.Inaddition,criticaltestparametersthathavetobemonitoredperiodicallyduringuseincludevolumeandtemperatureoftheDissolutionmedium,rotationspeed(Apparatus1andApparatus2),diprate(Apparatus3),andflowrateofmedium(Apparatus4).溶出度測試儀器的適用性必須包括與上述各儀器在尺寸和限度上的一致性。另外，必須在使用過程中定期觀測的關(guān)鍵測試參數(shù)包括：溶出介質(zhì)的溫度和體積，轉(zhuǎn)速(第1法和第2法)，浸沒

47、頻率(第3法)和溶出介質(zhì)流速(第4法)。Determinetheacceptableperformanceofthedissolutiontestassemblyperiodically.*ThesuitabilityfortheindividualapparatusisdemonstratedbythePerformanceverificationtest.定期檢測溶出度測試設備的性能。*單個設備的適用性由性能驗證測試給出。Performanceverificationtest,Apparatus1andApparatus2:TestUSPPrednisoneTabletsRSaccordi

48、ngtotheoperatingconditionsspecified.Theapparatusissuitable訐theresultsobtainedarewithintheacceptablerangestatedinthetechnicaldatasheetspecifictothelotusedandtheapparatustested.性能驗證測試，第1法和第2法：根據(jù)規(guī)定的操作條件測試USP強的松片RS。如果結(jié)果在技術(shù)數(shù)據(jù)表上該批次和所用儀器的的可接受范圍內(nèi)，則設備是適用的。Performanceverificationtest,Apparatus3:Tocome.性能驗證測試，

49、第3法待續(xù)Performanceverificationtest,Apparatus4:Tocome.十性能驗證測試，第4法待續(xù),PROCEDURE測試方法Apparatus1andApparatus2第1法和第2法IMMEDIATE-RELEASEDOSAGEFORMS速釋制劑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.將各論中給出的溶出介質(zhì)量（1%）加入到*規(guī)定的*容器中，組裝好設備，平衡溶出介質(zhì)溫度在370.5

53、C，移出溫度計。將1單位劑量的藥品小心加入設備中，注意避免表面產(chǎn)生氣泡。立即按照*各論中規(guī)定的*速率開動設備。在規(guī)定的時間間隔或給定的時間點，從溶出介質(zhì)液面以下和溶出籃或槳葉頂端之間，離杯壁至少1cm的區(qū)域取出一份試樣。注：如果規(guī)定有多次取樣，以等體積的37C溶出介質(zhì)補償所取液體?；蛘?，如果有證明不需要補償介質(zhì)，在計算中修正溶液體積的變化。在檢測中保持容器加蓋，并以適當?shù)念l率驗證溶液的溫度。按照*各論中規(guī)定的*合適的方法進行分析3。重復試驗以測試更多的劑量單元。Ifautomatedequipmentisusedforsamplingortheapparatusisotherwisemodif

54、ied,verificationthatthemodifiedapparatuswillproduceresultsequivalenttothoseobtainedwiththestandardapparatusdescribedinthisgeneralchapterisnecessary.如果使用自動化裝置取樣或者設備在其他方面做出了更改，需要進行驗證以顯示修改后的設備可以給出與通用章節(jié)中的標準設備等效的結(jié)果。Dissolutionmedium:Asuitabledissolutionmediumisused.Usethesolventspecified+intheindividualm

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

56、hedissolutionresults,dissolvedgasesshouldberemovedbeforetesting.4溶出介質(zhì)：使用合適的溶出介質(zhì)。使用*各論中*規(guī)定的溶劑。所規(guī)定的體積指在20和25C之間所測的值。如果溶出介質(zhì)是緩沖液，調(diào)整緩沖液以保證緩沖液的pH值在*各論中*規(guī)定的pH值的0.05以內(nèi)。注：溶解的氣體可以導致氣泡的生成，從而改變測試結(jié)果。如果溶解的氣體會影響溶出結(jié)果，在測試前除去溶解的氣體4。Time:Whereasingletimespecificationisgiven,thetestmaybeconcludedinashorterperiod訐thereq

57、uirementfortheminimumamountdissolvedismet.Specimensaretobewithdrawnonlyatthestatedtimes,withinatoleranceof2%.時間：當規(guī)定了單一的時間時，如果最小溶出量已達到，測試可以提前結(jié)束。試樣必須在所述時間的2%范圍內(nèi)取出。+Procedureforapooledsampleforimmediate-releasedosageforms:UsethisprocedurewhereProcedureforaPooledSampleisspecifiedintheindividualmonograph

58、.ProceedasdirectedforImmediate-ReleaseDosageFormsinApparatus1andApparatus2intheProceduresection.Combineequalvolumesofthefilteredsolutionsofthesixortwelveindividualspecimenswithdrawn,andusethepooledsampleasthetestspecimen.Determinetheaverageamountoftheactiveingredientdissolvedinthepooledsample.+速釋制劑集

59、合樣品測試方法：如果各論中有規(guī)定測試集合樣品，使用本方法。按照測試方法章節(jié)中速釋制劑第1法和第2法進行。集中全部所測的6或12個單獨物種的等體積的溶劑，過濾，使用集合樣品作為被測物種，測定集合樣品中各活性成分的平均溶出量。EXTENDED-RELEASEDOSAGEFORMS緩釋制劑ProceedasdirectedforImmediate-ReleaseDosageForms.按照速釋制劑的方法進行。Dissolutionmedium:ProceedasdirectedforImmediate-ReleaseDosageForms.溶出介質(zhì)：按照立即釋放制劑的方法進行。Time:Thetes

60、t-timepoints,generallythree,areexpressedinhours.時間：測試時間點，通常是3個，以小時為單位。DELAYED-RELEASEDOSAGEFORMSNOTACCEPTEDBYTHEJAPANESEPHARMACOPOEIA日本藥典未收錄的遲釋制劑UseMethodAorMethodBandtheapparatusspecified+intheindividualmonograph*.Alltesttimesstatedaretobeobservedwithinatoleranceof%,unlessotherwisespecified.按照各論中的規(guī)