美国药典溶解性Word版

DESCRIPTIONANDSOLUBILITYDescriptionandRelativeSolubilityofUSPandNFArticlesThe“description”and“solubility”statementspertainingtoanarticle(formerlyincludedintheindividualmonograph)aregeneralinnature.Theinformationisprovidedforthosewhouse,prepare,anddispensedrugs,solelytoindicatedescriptiveandsolubilitypropertiesofanarticlecomplyingwithmonographstandards.Thepropertiesarenotinthemselvesstandardsortestsforpurityeventhoughtheymayindirectlyassistinthepreliminaryevaluationoftheintegrityofanarticle.TasteandOdorOrganolepticcharacteristicsareindicatedinmanyinstancesbecausetheymaybeusefulanddescriptivepropertiesofsubstances.However,theyarenotmeanttobeappliedastestsforidentifyingmaterials.Theinclusionofodorortasteamongotherdescriptivepropertiesmayaidinidentifyingthecausativeagentfollowingaccidentalexposuretoorcontactwithasubstance.Thisinformationisprovidedasawarningortomakeanindividualawareofsensationsthatmaybeencountered.Theuseofodorortasteasatestforidentificationorcontentisstronglydiscouraged.Thecharacteristicodorofavolatilesubstancebecomesapparentimmediatelyonopeningacontainerofit.Theodormaybeagreeable(e.g.,PeppermintOil),unpleasant(e.g.,SulfurDioxide),orpotentiallyhazardousonprolongedexposure(e.g.,CoalTar).Moreover,anunexpectedodormaybeencounteredifthecharacteristicsofasubstancearenotknownorifacontainerisincorrectlylabeled.Consequently,containersofsuchsubstancesshouldbeopenedcautiously,preferablyinawell-ventilatedfumehood.Acharacteristictasteorsensationproducedintheoralcavitylikewiseisapparentiftracesofresiduematerialsonfingersareinadvertentlybroughtintocontactwiththetongueoradjacentmucosaltissues.SolubilityOnlywhereaspecial,quantitativesolubilitytestisgivenintheindividualmonograph,andisdesignatedbyatestheading,isitatestforpurity.TheapproximatesolubilitiesofPharmacopeialandNationalFormularysubstancesareindicatedbythedescriptivetermsintheaccompanyingtable.Theterm“miscible”asusedinthisPharmacopeiapertainstoasubstancethatyieldsahomogeneousmixturewhenmixedinanyproportionwiththedesignatedsolvent.DescriptiveTermPartsofSolventRequiredfor1PartofSoluteVerysolubleLessthan1FreelysolubleFrom1to10SolubleFrom10to30SparinglysolubleFrom30to100SlightlysolubleFrom100to1000VeryslightlysolubleFrom1000to10,000Practicallyinsoluble,orInsoluble10,000andoverSolublePharmacopeialandNationalFormularyarticles,whenbroughtintosolution,mayshowtracesofphysicalimpurities,suchasminutefragmentsoffilterpaper,fibers,andotherparticulatematter,unlesslimitedorexcludedbydefinitetestsorotherspecificationsintheindividualmonographs.1171PHASE-SOLUBILITYANALYSISPhase-solubilityanalysisisthequantitativedeterminationofthepurityofasubstancethroughtheapplicationofprecisesolubilitymeasurements.Atagiventemperature,adefiniteamountofapuresubstanceissolubleinadefinitequantityofsolvent.Theresultingsolutionissaturatedwithrespecttotheparticularsubstance,butthesolutionremainsunsaturatedwithrespecttoothersubstances,eventhoughsuchsubstancesmaybecloselyrelatedinchemicalstructureandphysicalpropertiestotheparticularsubstancebeingtested.Constancyofsolubility,likeconstancyofmeltingtemperatureorotherphysicalproperties,indicatesthatamaterialispureorisfreefromforeignadmixtureexceptintheuniquecaseinwhichthepercentagecompositionofthesubstanceundertestisindirectratiotosolubilitiesoftherespectivecomponents.Conversely,variabilityofsolubilityindicatesthepresenceofanimpurityorimpurities.Phase-solubilityanalysisisapplicabletoallspeciesofcompoundsthatarecrystallinesolidsandthatformstablesolutions.Itisnotreadilyapplicabletocompoundsthatformsolidsolutionswithimpurities.Thestandardsolubilitymethodconsistsofsixdistinctsteps:(1)mixing,inaseriesofseparatesystems,increasingquantitiesofmaterialwithmeasured,fixedamountsofasolvent;(2)establishmentofequilibriumforeachsystematidenticalconstanttemperatureandpressure;(3)separationofthesolidphasefromthesolutions;(4)determinationoftheconcentrationofthematerialdissolvedinthevarioussolutions;(5)plottingtheconcentrationofthedissolvedmaterialsperunitofsolvent(y-axisorsolutioncomposition)againsttheweightofmaterialperunitofsolvent(x-axisorsystemcomposition);and(6)extrapolationandcalculation.SolventsApropersolventforphase-solubilityanalysismeetsthefollowingcriteria:(1)Thesolventisofsufficientvolatilitythatitcanbeevaporatedundervacuum,butisnotsovolatilethatdifficultyisexperiencedintransferringandweighingthesolventanditssolutions.Normally,solventshavingboilingpointsbetween60and150aresuitable.(2)Thesolventdoesnotadverselyaffectthesubstancebeingtested.Solventsthatcausedecompositionorreactwiththetestsubstancearenottobeused.Solventsthatsolvateorformsaltsaretobeavoided,ifpossible.(3)Thesolventisofknownpurityandcomposition.Carefullypreparedmixedsolventsarepermissible.Traceimpuritiesmayaffectsolubilitygreatly.(4)Asolubilityof10mgto20mgpergisoptimal,butawiderworkingrangecanbeused.Apparatus*(​http:​/​​/​www.uspbpep.com​/​usp32​/​pub​/​data​/​v32270​/​usp32nf27s0_c1171.html"\l"usp32nf27s0_fc117101​)Constant-TemperatureBath—Useaconstant-temperaturebaththatiscapableofmaintainingthetemperaturewithin±0.1andthatisequippedwithahorizontalshaftcapableofrotatingatapproximately25rpm.TheshaftisequippedwithclampstoholdtheAmpuls.Alternatively,thebathmaycontainasuitablevibrator,capableofagitatingtheampulsat100to120vibrationspersecond,andequippedwithashaftandsuitableclampstoholdtheampuls.Ampuls—Use15-mLampulsofthetypeshownintheaccompanyingillustration(​http:​/​​/​www.uspbpep.com​/​usp32​/​pub​/​data​/​v32270​/​usp32nf27s0_c1171.html"\l"usp32nf27s0_ic11711​).Othercontainersmaybeusedprovidedthattheyareleakproofandotherwisesuitable.HYPERLINK"http://www.uspbpep.com/usp32/pub/data/images/v32270/g-1087.gif"INCLUDEPICTURE"http://www.uspbpep.com/usp32/pub/data/images/v32270/g-1087.gif"\*MERGEFORMATAmpul(left)andSolubilityFlask(right)UsedinPhase-SolubilityAnalysisSolubilityFlasks—Usesolubilityflasksofthetypeshownintheaccompanyingillustration(​http:​/​​/​www.uspbpep.com​/​usp32​/​pub​/​data​/​v32270​/​usp32nf27s0_c1171.html"\l"usp32nf27s0_ic11711​).Procedurenote—Makeallweighingswithin±10µg.SystemComposition—Weighaccurately,ing,notlessthan7scrupulouslycleaned15-mLampuls.Weighaccurately,ing,increasinglylargeramountsofthetestsubstanceintoeachoftheampuls.Theweightofthetestsubstanceisselectedsothatthefirstampulcontainsslightlylessmaterialthanwillgointosolutionin5mLoftheselectedsolvent,thesecondampulcontainsslightlymorematerial,andeachsubsequentampulcontainsincreasinglymorematerialthanmeetstheindicatedsolubility.Transfer5.0mLofthesolventtoeachoftheampuls,coolinadryice–acetonemixture,andseal,usingadouble-jetair-gasburnerandtakingcaretosaveallglass.Allowtheampulsandtheircontentstocometoroomtemperature,andweightheindividualsealedampulswiththecorrespondingglassfragments.Calculatethesystemcomposition,inmgperg,foreachampulbytheformula:1000(W2–W1)/(W3–W2)inwhichW2istheweightoftheampulplustestsubstance,W1istheweightoftheemptyampul,andW3istheweightofampulplustestsubstance,solvent,andseparatedglass.Equilibration—Thetimerequiredforequilibrationvarieswiththesubstance,themethodofmixing(rotationorvibration),andthetemperature.Normally,equilibriumisobtainedmorerapidlybythevibrationmethod(1to7days)thanbytherotationalmethod(7to14days).Inordertodeterminewhetherequilibrationhasbeeneffected,1ampul,i.e.,thenexttothelastintheseries,maybewarmedto40toproduceasupersaturatedsolution.Equilibrationisensuredifthesolubilityobtainedonthesupersaturatedsolutionfallsinlinewiththetestspecimensthatapproachequilibriumfromanundersaturatedsolution.SolutionComposition—Afterequilibration,placetheampulsverticallyinarackintheconstant-temperaturebath,withthenecksoftheampulsabovethewaterlevel,andallowthecontentstosettle.Opentheampuls,andremoveaportiongreaterthan2mLfromeachbymeansofapipetequippedwithasmallpledgetofcottonmembraneorothersuitablefilter.Transfera2.0-mLaliquotofclearsolutionfromeachampultoamarked,taredsolubilityflask,andweigheachflaskplusitssolutiontoobtaintheweightofthesolution.Cooltheflasksinadryice–acetonebath,andthenevaporatethesolventinvacuum.Graduallyincreasethetemperaturetoatemperatureconsistentwiththestabilityofthecompound,anddrytheresiduetoconstantweight.Calculatethesolutioncomposition,inmgperg,bytheformula:1000(F3–F1)/(F2–F3)inwhichF3istheweightoftheflaskplusresidue,F1istheweightofthesolubilityflask,andF2istheweightoftheflaskplussolution.CalculationForeachportionofthetestsubstancetaken,plotthesolutioncompositionastheordinateandthesystemcompositionastheabscissa.Asshownintheaccompanyingdiagram,(​http:​/​​/​www.uspbpep.com​/​usp32​/​pub​/​data​/​v32270​/​usp32nf27s0_c1171.html"\l"usp32nf27s0_ic11712​)HYPERLINK"http://www.uspbpep.com/usp32/pub/data/images/v32270/g-1088.gif"INCLUDEPICTURE"http://www.uspbpep.com/usp32/pub/data/images/v32270/g-1088.gif"\*MERGEFORMATTypicalPhase-SolubilityDiagramthepointsforthosecontainers,frequentlyonlyone,thatrepresentatruesolutionfallonastraightline(AB)withaslopeof1,passingthroughtheorigin;thepointscorrespondingtosaturatedsolutionsfallonanotherstraightline(BC),theslope,S,ofwhichrepresentstheweightfractionofimpurityorimpuritiespresentinthetestsubstance.Failureofpointstofallonastraightlineindicatesthatequilibriumhasnotbeenachieved.Acurveindicatesthatthematerialundertestmaybeasolidsolution.Calculatethepercentagepurityofthetestsubstancebytheformula:100–100S.Theslope,S,maybecalculatedgraphicallyorbyleast-squarestreatmentforbestfitoftheexperimentalvaluestoastraightline.Thesolubilityofthemaincomponentisobtainedbyextendingthesolubilityline(BC)throughthey-axis.Thepointofinterceptiononthey-axisistheextrapolatedsolubility,inmgperg,andisaconstantforagivencompound.PurificationTechniqueSincethesolventphaseinallcombinationsofsolventandsolutethatareusedtoconstructsegmentBCofaphase-solubilitydiagramcontainsessentiallyalltheimpuritiesoriginallypresentinthesubstanceunderanalysis,whereasthesolidphaseisessentiallyfreefromimpurities,phase-solubilityanalysiscanbeusedtopreparepurereferencespecimensofdesiredcompoundsaswellasconcentratesofimpuritiesfromsubstancesotherwiseconsideredpure.Asimplemodificationofthistechniquecanbeusedtoaccomplishthesepurposeswithconsiderablylesseffortthanisusuallyrequiredforrigorousphase-solubilityanalysis.Inpractice,aweighedamountoftestspecimenissuspendedinanonreactivesolventofsuitablecompositionandamountsothatabout10%ofthematerialisdissolvedatequilibrium.Thesuspensionissealed(ascrew-capvialisusuallyadequate)andshakenatroomtemperatureuntilequilibriumisattained(usually24hoursissufficientforthispurpose).Themotherliquoristhendrawnoffandevaporatedatornearroomtemperaturetodryness.Sincethemotherliquorcontainedessentiallyalltheimpuritiesthatwerepresentinthespecimen,theresiduehasbeenconcentratedwithrespecttotheimpuritiesroughlyinproportiontotheratiooftheweightofspecimentakentotheweightofsolidsdissolvedinthevolumeofsolventused.Theundissolvedcrystalsremainingafterwithdrawalofthemotherliquorareusuallysufficientlypuretobeusedasareferencestandardafterappropriaterinsinganddrying.* AvailablefromHansonResearchCorp.,19727BahamaSt.,P.O.Box35,Northridge,CA91324.AuxiliaryInformation—PleasecheckforyourquestionintheFAQs(​http:​/​​/​www.uspnf.com​/​uspnf​/​scienceFAQ.html"\t"_new​)beforecontactingUSP.Topic/QuestionContactExpertCommitteeGeneralChapterHoracioN.Pappa,Ph.D.(​mailto:hp@usp.org​)SeniorScientistandLatinAmericanLiaison1-301-816-8319(GC05)GeneralChapters05USP32–NF27Page687（注：可编辑下载，若有不当之处，请指正，谢谢!）推荐精选推荐精选推荐精选