溶出度檢查法美國藥典USP-7115/20<711>DISSOLUTION溶出度(USP39-NF34Page540)Generalchapter

Dissolution

<711>

isbeingharmonizedwiththecorrespondingtextsofthe

EuropeanPharmacopoeia

and/orthe

JapanesePharmacopoeia.Thesepharmacopeiashaveundertakentonotmakeanyunilateralchangetothisharmonizedchapter.通則<711>溶出度與歐盟藥典和日本藥典中的相應部分相統一。這三部藥典承諾不做單方面的修改。Portionsofthepresentgeneralchaptertextthatarenational

USP

text,andthereforenotpartoftheharmonizedtext,aremarkedwithsymbolstospecifythisfact.本章中的部分文字為本國USP內容，并沒有與其他藥典統一。此部分以（

）標注。Thistestisprovidedtodeterminecompliancewiththedissolutionrequirements

wherestatedintheindividualmonograph

fordosageformsadministeredorally.Inthisgeneralchapter,adosageunitisdefinedas1tabletor1capsuleortheamountspecified.

Ofthetypesofapparatusdesignsdescribedherein,usetheonespecifiedintheindividualmonograph.Wherethelabelstatesthatanarticleisentericcoatedandadissolutionordisintegrationtestdoesnotspecificallystatethatitistobeappliedto

delayed-release

articlesandisincludedintheindividualmonograph,theprocedureandinterpretationgivenfor

Delayed-ReleaseDosageForms

areapplied,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定。本章中，除另有規定外，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，使用各論中規定的種類。除各論中另有規定外，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Ifthedosageformcontaininggelatindoesnotmeetthecriteriaintheappropriate

AcceptanceTable

(see

Interpretation,

Immediate-ReleaseDosageForms,

Extended-ReleaseDosageForms,or

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

AcceptanceTable.Itisnotnecessarytocontinuetestingthroughthelaststage(upto24units)whencriteriaarenotmetduringthefirststagetesting,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），因為存在明膠交聯結合作用，它的溶解過程與外加的媒介酶是重復的，見下面的描述，并且溶解結果可以通過適當的驗收表的開始的第一階段標準進行評估。如果溶出結果不滿足第一階段的測試標準，那么就沒有必要繼續測試到最后階段，并且也證明了明膠交聯結合作用的存在。Gelatin,inthepresenceofcertaincompoundsand/orincertainstorageconditions,includingbutnotrestrictedtohighhumidityandtemperature,maypresentcross-linking.Apelliclemayformontheexternaland/orinternalsurfaceofthegelatincapsuleshelloronthedosageformthatpreventsthedrugfrombeingreleasedduringdissolutiontesting(seemoreinformationin

Capsules—DissolutionTestingandRelatedQualityAttributes

<1094>).明膠，存在于某一處方和/或某一儲存條件下，如：高溫高濕，可能存在明膠交聯結合作用。在膠囊殼或其他劑型的外表面和/或內表面形成一層膜阻止溶出試驗過程中藥物的釋放（見膠囊-溶出度檢測和相關質量屬性<1094>

）。Note

—

Allreferencestoachapterabove

<1000>

areforinformationpurposesonly,foruseasahelpfulresource.Thesechaptersarenotmandatoryunlessexplicitlycalledoutforthisapplication.注-超過<1000>章節的所有引用應用的目的僅為提供參考信息。這些章節是非強制的，除非另有規定。DissolutionMediumwithpH

≤4.0pH

≤4.0的溶出介質

Enzyme:

Pepsin,activitydeterminedbytheprocedurein

purifiedpepsin,inthe

ReagentSpecifications

section

Shaftandbasketcomponentsofthestirringelementarefabricatedofstainlesssteel,type316,orotherinertmaterial,tothespecificationsshownin

Figure1.Abaskethavingagoldcoatingofabout0.0001inch(2.5μm)thickmaybeused.Adosageunitisplacedinadrybasketatthebeginningofeachtest.Thedistancebetweentheinsidebottomofthevesselandthebottomofthebasketismaintainedat25±2mmduringthetest.轉軸和籃筐組件由316號不銹鋼或者其他惰性材料制成，尺寸如圖1所示。可使用鍍金厚度0.0001英寸（2.5μm）的籃筐。開始檢測時，將一劑藥品至于干燥的籃筐中。在測試過程中，溶出杯底部到籃筐底部的距離應保持在25±2mm。Figure1.Basketstirringelement.圖1.轉籃組成Apparatus2(PaddleApparatus)第2法（槳法）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法中的設備，除了使用一個由葉片和轉軸組成的槳作為攪拌單元。轉軸與溶出杯的縱軸在任意部位不得相差差過2mm，轉動平滑，無明顯搖晃以至于影響檢測結果。葉片的垂直中性線穿過轉軸的軸線，葉片的下緣與轉軸底部平齊。槳的尺寸應符合圖2中的規定。在測試過程中，葉片底部與溶出杯底部的距離應保持在25±2mm。金屬或硬質的葉片和轉軸應是一個整體。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。可以在槳葉和轉軸上涂布合適的涂層以使其為惰性。在槳葉開始旋轉前，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。其他經驗證的沉子也可以使用。Figure2.Paddlestirringelement.圖2.攪拌槳組成Figure2a.Alternativesinker.Alldimensionsareexpressedinmm.圖2a.可選的沉降籃（單位均為mm）Apparatus3(ReciprocatingCylinder)第3法（往復圓筒法）notacceptedbythejapanesepharmacopoeia日本藥典未收錄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）；由合適的非吸附，不反應材料制成的篩網，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37±0.5℃。儀器的任何部件，以及儀器所處的環境，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定值的±5%范圍內。儀器最好可以在檢測過程中觀察到樣品和往復圓筒。玻璃杯配有蒸發帽，在檢測中一直蓋在玻璃杯上。除另有規定外，各部分的尺寸如圖3所示。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）Theassemblyconsistsofareservoirandapumpforthe

Dissolutionmedium;aflow-throughcell;andawaterbaththatmaintainstheDissolutionmedium

at37±0.5°.Usethespecifiedcellsize

asgivenintheindividualmonograph

.所用設備包含一個溶出介質的容器和相應的泵，一個流通池和水浴。水浴將溶出介質保持在37±0.5℃。使用各論中規定的尺寸。Thepumpforcesthe

Dissolutionmedium

upwardthroughtheflow-throughcell.Thepumphasadeliveryrangebetween240and960mL/h,withstandardflowratesof4,8,and16mL/min.Itmustdeliveraconstantflow(±5%ofthenominalflowrate);theflowprofileissinusoidalwithapulsationof120±10pulses/min.Apumpwithoutpulsationmayalsobeused.Dissolutiontestproceduresusingaflow-throughcellmustbecharacterizedwithrespecttorateandanypulsation.泵將溶出介質推動，向上通過流通池。泵的傳輸能力在240到960mL每小時之間，標準速率為4，8，16mL每分鐘。泵的流速必須均勻（名義流量的±5%以內）。泵的流量特性曲線應為正弦波，脈沖為每分鐘120±10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(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（見圖4和圖5）垂直安放，配有過濾系統（在各論中規定）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37±0.5℃的水浴中。Figure4.Apparatus4:largecellfortabletsandcapsules(top);tabletholderforthelargecell(bottom).(Allmeasurementsareexpressedinmmunlessnotedotherwise.)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。）Figure5.Apparatus4:smallcellfortabletsandcapsules(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-ringstoassemblethecell.Thepumpisseparatedfromthedissolutionunittoshieldthelatteragainstanyvibrationsoriginatingfromthepump.Thepositionofthepumpshouldnotbeonalevelhigherthanthereservoirflasks.Tubeconnectionsareasshortaspossible.Usesuitablyinerttubing,suchaspolytef,withabouta1.6-mminnerdiameterandchemicallyinert,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，內徑1.6mm。法蘭連接也應為化學惰性。apparatussuitability設備適用性Thedeterminationofsuitabilityofatestassemblytoperformdissolutiontestingmustincludeconformancetothedimensionsandtolerancesoftheapparatusasgivenabove.Inaddition,criticaltestparametersthathavetobemonitoredperiodicallyduringuseincludevolumeandtemperatureofthe

Dissolutionmedium,rotationspeed(Apparatus1

and

Apparatus2),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鍵測試參數包括：溶出介質的溫度和體積，轉速（第1法和第2法），浸沒頻率（第3法）和溶出介質流速（第4法）。Determinetheacceptableperformanceofthedissolutiontestassemblyperiodically.

Thesuitabilityfortheindividualapparatusisdemonstratedbythe

Performanceverificationtest.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:

Test

USPPrednisoneTabletsRS

accordingtotheoperatingconditionsspecified.Theapparatusissuitableiftheresultsobtainedarewithintheacceptablerangestatedinthetechnicaldatasheetspecifictothelotusedandtheapparatustested.性能驗證測試，第1法和第2法：根據規定的操作條件測試USP強的松片RS。如果結果在技術數據表上該批次和所用儀器的的可接受范圍內，則設備是適用的。Performanceverificationtest,Apparatus3:

[Tocome.]性能驗證測試，第3法——[待續]Performanceverificationtest,Apparatus4:

[Tocome.]

性能驗證測試，第4法——[待續]

PROCEDURE測試方法Apparatus1andApparatus2第1法和第2法immediate-releasedosageforms速釋制劑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.將各論中給出的溶出介質量（±1%）加入到規定的容器中，組裝好設備，平衡溶出介質溫度在37±0.5℃，移出溫度計。將1單位劑量的藥品小心加入設備中，注意避免表面產生氣泡。立即按照各論中規定的速率開動設備。在規定的時間間隔或給定的時間點，從溶出介質液面以下和溶出籃或槳葉頂端之間，離杯壁至少1cm的區域取出一份試樣。[注：如果規定有多次取樣，以等體積的37℃溶出介質補償所取液體。或者，如果有證明不需要補償介質，在計算中修正溶液體積的變化。在檢測中保持容器加蓋，并以適當的頻率驗證溶液的溫度。]按照各論中規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。Ifautomatedequipmentisusedforsamplingortheapparatusisotherwisemodified,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中的標準設備等效的結果。Dissolutionmedium:

Asuitabledissolutionmediumisused.Usethesolventspecified

intheindividualmonograph

.Thevolumespecifiedreferstomeasurementsmadebetween20°and25°.Ifthe

Dissolutionmedium

isabufferedsolution,adjustthesolutionsothatitspHiswithin0.05unitofthespecifiedpH

givenintheindividualmonograph

.

[

Note

—

Dissolvedgasescancausebubblestoform,whichmaychangetheresultsofthetest.Ifdissolvedgasesinfluencethedissolutionresults,dissolvedgasesshouldberemovedbeforetesting.4

]溶出介質：使用合適的溶出介質。使用各論中規定的溶劑。所規定的體積指在20和25℃之間所測的值。如果溶出介質是緩沖液，調整緩沖液以保證緩沖液的pH值在各論中規定的pH值的0.05以內。[注：溶解的氣體可以導致氣泡的生成，從而改變測試結果。如果溶解的氣體會影響溶出結果，在測試前除去溶解的氣體4。]Time:

Whereasingletimespecificationisgiven,thetestmaybeconcludedinashorterperiodiftherequirementfortheminimumamountdissolvedismet.Specimensaretobewithdrawnonlyatthestatedtimes,withinatoleranceof±2%.時間：當規定了單一的時間時，如果最小溶出量已達到，測試可以提前結束。試樣必須在所述時間的±2%范圍內取出。

Procedureforapooledsampleforimmediate-releasedosageforms:

Usethisprocedurewhere

ProcedureforaPooledSample

isspecifiedintheindividualmonograph.Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2

intheProcedure

section.Combineequalvolumesofthefilteredsolutionsofthesixortwelveindividualspecimenswithdrawn,andusethepooledsampleasthetestspecimen.Determinetheaverageamountoftheactiveingredientdissolvedinthepooledsample.

速釋制劑集合樣品測試方法：如果各論中有規定測試集合樣品，使用本方法。按照測試方法章節中速釋制劑第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Proceedasdirectedfor

Immediate-ReleaseDosageForms.按照速釋制劑的方法進行。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms.溶出介質：按照立即釋放制劑的方法進行。Time:

Thetest-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Use

MethodA

or

MethodB

andtheapparatusspecified

intheindividualmonograph

.Alltesttimesstatedaretobeobservedwithinatoleranceof±2%,unlessotherwisespecified.按照各論中的規定，使用方法A或方法B。除另有規定外，所有測試時間與規定相差不得過±2%。MethodAProcedure

(unlessotherwisedirected

intheindividualmonograph)

方法A程序（除各論中另有規定外）acidstage酸階段Place750mLof0.1Nhydrochloricacidinthevessel,andassembletheapparatus.Allowthemediumtoequilibratetoatemperatureof37±0.5°.Place1dosageunitintheapparatus,coverthevessel,andoperatetheapparatusatthespecifiedrate

giveninthemonograph

.向容器中加入0.1N的鹽酸750mL，組裝設備。將介質平衡在37±0.5℃。將1單位劑量的藥品加入設備中，蓋上容器，依照各論中規定的速率啟動設備。After2hofoperationin0.1Nhydrochloricacid,withdrawanaliquotofthefluid,andproceedimmediatelyasdirectedinthe

BufferStage.在0.1N的鹽酸中攪拌2小時后，吸取一份試樣溶液，然后立即按照緩沖液階段的說明繼續操作。Performananalysisofthealiquotusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.

以適合的方法測試試樣。測試方法在各論中給出。bufferstage緩沖液階段[

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：加入緩沖液和調節pH的操作應在5分鐘內完成。]設備在各論中規定的速率下運行，向容器中加入250mL預先平衡在37±0.5℃的0.20M的磷酸鈉。必要時用2N的鹽酸或2N的氫氧化鈉調節pH至6.8±0.05。繼續運轉45分鐘或各論中給定的時間。到時間后，吸取一份試樣溶液，以適合的方法測試。測試方法在各論中給出。如果緩沖液階段的最小溶出量已提前達到，測試可以提前結束。MethodBProcedure

(unlessotherwisedirected

intheindividualmonograph)

方法B程序（除各論中另有規定外）acidstage酸階段Place1000mLof0.1Nhydrochloricacidinthevessel,andassembletheapparatus.Allowthemediumtoequilibratetoatemperatureof37±0.5°.Place1dosageunitintheapparatus,coverthevessel,andoperatetheapparatusattheratespecified

inthemonograph

.After2hofoperationin0.1Nhydrochloricacid,withdrawanaliquotofthefluid,andproceedimmediatelyasdirectedinthe

BufferStage.向容器中加入0.1N的鹽酸1000mL，組裝設備。將介質平衡在37±0.5℃。將1單位劑量的藥品加入設備中，蓋上容器，依照各論中規定的速率啟動設備。在0.1N的鹽酸中攪拌2小時后，吸取一份試樣溶液，然后立即按照緩沖液階段的說明繼續操作。Performananalysisofthealiquotusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.

以適合的方法測試試樣。測試方法在各論中給出。bufferstage緩沖液階段[

Note

—

Forthisstageoftheprocedure,usebufferthatpreviouslyhasbeenequilibratedtoatemperatureof37±0.5°.

]

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

[Note

—

Thismayalsobeaccomplishedbyremovingfromtheapparatusthevesselcontainingtheacid,thenreplacingitwithanothervesselcontainingthebuffer,andtransferringthedosageunittothevesselcontainingthebuffer.

][注：此階段使用預先平衡在37±0.5℃的緩沖液。]抽干容器中的酸液，加入1000mLpH6.8的磷酸鹽緩沖液（0.1N鹽酸加0.20M磷酸鈉，3：1）。必要時用2N的鹽酸或2N的氫氧化鈉調節pH至6.8±0.05。[注：也可以將設備中盛裝酸液的容器移出，換以另一盛裝緩沖液的容器，將藥劑轉移到緩沖液容器中。]Continuetooperatetheapparatusfor45min,orforthespecifiedtime

givenintheindividualmonograph

.Attheendofthetimeperiod,withdrawanaliquotofthefluid,andperformtheanalysisusingasuitableassaymethod.

Theprocedureisspecifiedintheindividualmonograph.Thetestmaybeconcludedinashortertimeperiodthanthatspecifiedforthe

BufferStage

iftherequirementforminimumamountdissolvedismetatanearliertime.

繼續運轉45分鐘或各論中給定的時間。到時間后，吸取一份試樣溶液，以適合的方法測試。測試方法在各論中給出。如果緩沖液階段的最小溶出量已提前達到，測試可以提前結束。Apparatus3(ReciprocatingCylinder)第3法（往復圓筒法）notacceptedbythejapanesepharmacopoeiaimmediate-releasedosageforms日本藥典未收錄的速釋制劑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.將指定量的溶出介質加入到設備的每個容器中，組裝好設備，平衡溶出介質溫度在37±0.5℃，移出溫度計。在6個往復圓筒中分別加入1單位劑量的藥品，注意避免表面產生氣泡。立即按照各論中規定的速率開動設備。在上行和下行沖程中，往復圓筒移動的總距離為9.9到10.1cm。在規定的時間間隔或者每個給定的時間點，抬起往復圓筒，從溶出介質的表面到容器底部的中點區域取出一部分測試溶液。按照各論中的規定測試。必要時重復測試更多份的樣品。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.溶出介質：同第1法和第2法下立即釋放制劑項下處理。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.時間：同第1法和第2法下立即釋放制劑項下處理。extended-releasedosageforms緩釋制劑Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus3.同第3法下速釋制劑項下處理。Dissolutionmedium:

Proceedasdirectedfor

Extended-ReleaseDosageForms

in

Apparatus1andApparatus2.溶出介質：同第1法和第2法下緩釋制劑項下處理。Time:

Proceedasdirectedfor

Extended-ReleaseDosageForms

in

Apparatus1andApparatus2.時間：同第1法和第2法下緩釋制劑項下處理。delayed-releasedosageforms遲釋制劑Proceedasdirectedfor

Delayed-ReleaseDosageForms,MethodB

in

Apparatus1andApparatus2,usingonerowofvesselsfortheacidstagemediaandthefollowingrowofvesselsforthebufferstagemedia,andusingthevolumeofmediumspecified(usually300mL).同第1法和第2法下遲釋制劑方法B項下處理。酸性階段使用一排容器，緩沖液階段使用另一排容器。使用規定體積的介質（通常為300mL）。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.時間：同第1法和第2法下立即釋放制劑項下處理。Apparatus4(Flow-ThroughCell)第4法（流通池法）immediate-releasedosageforms速釋制劑Placetheglassbeadsintothecellspecified

inthemonograph

.Place1dosageunitontopofthebeadsor,ifspecified

inthemonograph

,onawirecarrier.Assemblethefilterhead,andfixthepartstogetherbymeansofasuitableclampingdevice.Introducebythepumpthe

Dissolutionmedium

warmedto37±0.5°throughthebottomofthecelltoobtaintheflowratespecified

intheindividualmonograph

andmeasuredwithanaccuracyof5%.Collecttheeluatebyfractionsateachofthetimesstated.Performtheanalysisasdirected

intheindividualmonograph

.Repeatthetestwithadditionaldosageformunits.依照規定將玻璃珠裝入流通池。將1單位劑量的藥品置于玻璃珠上。如果各論中另有規定，也可置于載具上。裝上過濾頭，用合適的夾子夾緊。平衡在37±0.5℃的溶出介質被泵由下而上泵入流通池，流速按各論中的規定，精確到5%。在每個給定的時間點收集浸出液。按照各論中的規定進行分析。重復試驗以測試更多的劑量單元。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.溶出介質：同第1法和第2法下立即釋放制劑項下處理。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus1andApparatus2.時間：同第1法和第2法下立即釋放制劑項下處理。extended-releasedosageforms緩釋制劑Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus4.同第4法立即釋放制劑項下處理。Dissolutionmedium:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus4.溶出介質：同第4法下立即釋放制劑項下處理。Time:

Proceedasdirectedfor

Immediate-ReleaseDosageForms

in

Apparatus4.時間：同第4法下立即釋放制劑項下處理。delayed-releasedosageforms遲釋制劑Proceedasdirectedfor

Delayed-ReleaseDosageForms

in

Apparatus1andApparatus2,usingthespecifiedmedia.同第1法和第2法下遲釋制劑項下處理。Time:

Proceedasdirectedfor

Delayed-ReleaseDosageForms

in

Apparatus1andApparatus2.時間：同第1法和第2法下遲釋制劑項下處理。

INTERPRETATION判斷Immediate-ReleaseDosageForms速釋制劑Unlessotherwisespecified

intheindividualmonograph

,therequirementsaremetifthequantitiesofactiveingredientdissolvedfromthedosageunitstestedconformto

AcceptanceTable1.Continuetestingthroughthethreestagesunlesstheresultsconformateither

S1

or

S2

.Thequantity,

Q,istheamountofdissolvedactiveingredient

specifiedintheindividualmonograph

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

AcceptanceTable1

arepercentagesofthelabeledcontentsothatthesevaluesand

Q

areinthesameterms.除各論中另有規定外，如果制劑單位中溶出的活性成分的量達到接受限度表1中的規定，認為合格。連續測試3個階段，除非結果符合S1或S2的限度。溶出量Q指各論中規定的活性成分溶出的量，以標示量的百分比表示。限度表1中的5%，15%和25%是指標示量的百分比，和Q相同。AcceptanceTable1接受限度表1Stage階段NumberTested樣品數量AcceptanceCriteria接受限度S16EachunitisNLT

Q+5%.每個單位不少于Q+5%.S26Averageof12units(S1+S2)is≥

Q,

andnounitis<Q-15%.12單位(S1+S2)的平均值大于等于Q，且任意一單位不少于Q-15%.S312Averageof24units(S1+S2+S3)is≥

Q,NMT2unitsare<Q

-15%,andnounitis<Q-25%.24單位(S1+S2+S3)的平均值大于等于Q，其中最多2單位少于Q-15%，沒有任一單位少于Q-25%.

Immediate-ReleaseDosageFormsPooledSample立即釋放制劑集合樣品Unlessotherwisespecifiedintheindividualmonograph,therequirementsaremetifthequantitiesofactiveingredientdissolvedfromthepooledsampleconformtotheaccompanying

AcceptanceTableforaPooledSample

.Continuetestingthroughthethreestagesunlesstheresultsconformateither

S

1

or

S

2

.Thequantity,

Q,istheamountofdissolvedactiveingredientspecifiedintheindividualmonograph,expressedasapercentageofthelabeledcontent.除各論中另有規定外，如果集合樣品中溶出的活性成分的量達到隨附的集合樣品接受限度表中的規定，認為合格。連續測試3個階段，除非結果符合S1或S2的限度。溶出量Q指各論中規定的活性成分溶出的量，以標示量的百分比表示。AcceptanceTableforaPooledSample集合樣品接受限度表Stage階段NumberTested樣品數量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緩釋制劑Unlessotherwisespecified

intheindividualmonograph

,therequirementsaremetifthequantitiesofactiveingredientdissolvedfromthedosageunitstestedconformto

AcceptanceTable2.Continuetestingthroughthethreelevelsunlesstheresultsconformateither

L

1

or

L

2.Limitsontheamountsofactiveingredientdissolvedareexpressedintermsofthepercentageoflabeledcontent.Thelimitsembraceeachvalueof

Qi,theamountdissolvedateachspecifiedfractionaldosinginterval.Wheremorethanonerangeisspecified

intheindividualmonograph

,theacceptancecriteriaapplyindividuallytoeachrange.除各論中另有規定外，如果制劑單位中溶出的活性成分的量達到接受限度表2中的規定，認為合格。連續測試3個等級，除非結果符合L1或L2的限度。活性成分溶出量的限度以標示量的百分比的形式給出。限度包含每個規定給藥間隔所測得的溶出量Qi。如果各論中規定了不止一個范圍，接受限度適用于每個范圍。AcceptanceTable2接受限度表2Level等級Number

Tested樣品數量Criteria限度L16Noindividualvalueliesoutsideeachofthestatedranges,andnoindividualvalueislessthanthestatedamountatthefinaltesttime.每個規定的范圍均無測量值超出限度，測試結束時沒有任何測量值小于規定溶出量。L26Theaveragevalueofthe12units(L1+L2)lieswithineachofthestatedrangesandisNLTthestatedamountatthefinaltesttime;noneis>10%oflabeledcontentoutsideeachofthestatedranges;andnoneis>10%ofthelabeledcontentbelowthestatedamountatthefinaltesttime.12個單元(L1+L2