脂肪乳剂理化性质和稳定性的影响因素浅析

。。、。R944A1673-6273201018-3581-04ApproachofFactorsInfluencingPhysico-chemicalPropertyandStabilityofLipidEmulsionsZHANGXiao-juan1△,LIZhu-wen1,LIShu2,MeiXing-guo3(1HigherVocationalInstitute,ChinaPharmaceuticalUniversityNanjing211198;2InstituteofRadiationMedicine,AcademyofMilitaryMedicalSciencesBeijing100850;3InstituteofPharmacologyandToxicology,AcademyofMilitaryMedicalSciencesBeijing100850)ABSTRACT:Lipidinjectableemulsionsaredispersionsoftwoimmiscibleliquids(oilphaseandwaterphase),theyincorporatewaternon-solubledrugs,stabilizedrugswhichtendtoundergohydrolysisandreducesideeffectsofvariouspotentdrugs.Theyrequireenergytobeformed,andarethermodynamicallyunstable.Theyaresubjectedtovariousinstableprocesseslikeaggregation,flocculation,coalescenceandhenceeventualphaseseparation.Thispapergavereviewontheformulation,preparationandpackage,etc,somemaininfluencingfactorsofthephysico-chemicalpropertyandstabilityoflipidemulsions.Keywords:Lipidemulsion;Submicroemulsion;Particlesize;StabilityChineseLibraryClassification:R944Documentcode:AArticleID:1673-6273(2010)18-3581-04E-mail:[e-mail]2010-05-212010-06-23(lipidemulsions)、、0.1～1μm(O/W)、[1]。、[2]。、。。、、。1(LCT)(MCT)、、、。。MuhannadJumaa[3]、、1。。DriscollDF[3]。[5]、Q10。5%、10%、15%20%。。2。。3581··[6]。FormigaF.R.[6]。。。[7]。。。HLB。JumaaM[8]、、30%。。。3。、、Pluron-ic-F68Tween80、、。MuhannadJumaa[9]。Pluronic-F68。Tween80。F68。2.。1Table1EffectofoilphaseonthestabilityoflipidemulsionsOilphaseConcentrationofoilphaseStabilityoflipidemulsionscastoroil20%Withhighviscosity,needhigherhomogenizationpressure;theparticlesizeincreasedafter3monthsanddeteriorated[3]sesameoil20%Stable[3]almondoil20%Stable[3]castoroil:soybeanoil(1:1)20%Stable[3]castoroil:MCT(1:1)20%Withlowerviscosity,needlowerhomogenizationpressure;stable[3]castoroil:MCT(1:1)20%Theconcentrationofcastoroilmore,thestabilityworse[3]castoroil:MCT(1:1)30%stable[3]MCT30%coalescence[4]soybeanoil20%All-in-Onenutrientadmixturedeteriorated[4]soybeanoil:saffloweroil(1:1)20%All-in-Onenutrientadmixturedeteriorated[4]soybeanoil:MCT(1:1)20%stable[4]Oliveoil:soybeanoil(1:1)20%stable[4]EmulsifierLipidemulsionsStabilityoflipidemulsionsPluronicF68SoybenoillipidemulsionStableaftersterilization[9]Tween80SoybenoillipidemulsionParticlesizeincreasedaftersterilization[9]CremophorELSoybenoillipidemulsionParticlesizeincreasedaftersterilization[9]PCSoybenoillipidemulsionWithalotofchangeinparticlesize,withmorefreefattyacids[10]PluronicF-127SoybenoillipidemulsionWithalittlechangeinparticlesize,withlessfreefattyacids[10]EPC-Tween80PrednimustinecastoroillipidemulsionWithbestdispersityandstability[11]SPC-PluronicF-127NaproxenlipidemulsionEmulsifierinfluencedthestabilityoflipidemusionssignificantly[12]2Table2Effectofemulsifieronthestabilityoflipidemulsions98%80%30%80%。LipoidE80Ovothin1803582··~100%LipoidE100Ovothin200[13]。4(zeta)。、。、、zeta。、。LevyMY[14]。pH7.8~8.0zeta。zeta[15]。0.03%zetazeta。zetazeta。YamaguchiMHosokawaT[16-17]Tween80zeta(-2.6mV)。。5、SolEmuls。、、[1]。。。。(overprocessing)[18]。。[15]60~100MPa10。6。(200nm)。6。、、pH。[19]31pH2pH8.50、9.50。pHpH8.5095%。pH8.50pHpH。。115℃30min。ShuaiShi[20]115℃30min、121℃8min、126℃3min。121℃8、10、15、2025min20min。。121℃15min。7。DriscollDF[21-23]20%24PFAT550.05%。。。[24]。8。。、[5,18,20]。。FangLi[25]3、、、。。3583··(References)[1],.[J].,2009,25(6):527-529LiuZhi-hong,SongHong-tao.Thedevelopmentoflipidemulsions[J].PharmJChinPLA,2009,25(6):527-529[2]TamilvananS.Oil-in-waterlipidemulsions:implicationsforparenteralandoculardeliveringsystems[J].ProgLipidRes,2004,43(6):489-533[3]MuhannadJ,MullerBW.Theeffectofoilcomponentsandhomoge-nizationconditionsonthephysicochemicalpropertiesandstabilityofparenteralfatemulsions[J].InternationalJournalofPharmaceutics,1998,163:81-89[4]DriscollDF,GiampietroK,WichelhausDP,etal.Physicochemicalsta-bilityassessmentsoflipidemulsionsofvaryingoilcomposition[J].ClinNutr,2001,Apr,20(2):151-7[5],,,.Q10[J].,2007,5(5)448-451DingYan-fei,YaoYao,TaoYu-fei,etal.Formulationandpharmac-erticalprocessofpreparingcoenzymeQ10submicronemulsionforintravenousadministration[J].CentralSouthPharmacy,2007,5(5)448-451(InChinese)[6]FormigaFR,FonsecaIAA,SouzaKB.Influenceofalipophilicdrugonthestabilityofemulsions:Animportantapproachonthedevelopmentoflipidiccarriers[J].IntJPharm,2007,344(1-2):158-160[7]NordénTP,SiekmannB,LundquistS,etal.Physicochemicalcharac-terisationofadrug-containingphospholipid-stabilisedo/wemulsionforintravenousadministration[J].EurJPharmSci,2001,13(4):393-401[8]JumaaM,MüllerBW.Formulatingandstabilityofbenzodiazepinesinanewlipidemulsionformulation[J].Pharmazie,2002,57(11):740-3[9]MuhannadJ,MullerBW.Thestabilizationofparenteralfatemulsionusingnon-ionicABAcopolymersurfactant[J].InternationalJournalofPharmaceutics,1998,174:29-37[10]SuzukiY,MasumitsuY,OkudairaK.Theeffectsofemul