凍干工藝的優(yōu)化.ppt

OptimizationoftheLyophilizationorFreezeDryingProcess凍干工藝的優(yōu)化,DefinitionofLyophilization凍干的定義,Astabilizingprocessinwhichtheproductisfirstfrozenandthentheamountofsolventisremovedfirstbysublimationandthenbydesorptiontovaluesthatwillnolongersupportbiologicalgrowthorchemicalreactions.凍干是一個(gè)使物質(zhì)穩(wěn)定化的過程，在該過程中，首先使產(chǎn)品冷凍，然后將溶劑升華和解吸附，使產(chǎn)品中的含水量減少到不足以支持生物生長和發(fā)生化學(xué)反應(yīng)的程度,DefinitionofFreezeDrying冷凍干燥的定義,Freezedryingisastabilizingprocessinwhichthereisfirstcrystallizationofthesolventtoformastructureintheproductandthentheamountofsolventisremovedfirstbysublimationandthenbydesorptiontovaluesthatwillnolongersupportbiologicalgrowthorchemicalreactions.冷凍干燥是一個(gè)是物質(zhì)穩(wěn)定的過程，在該過程中，凍干的溶劑先結(jié)晶，在產(chǎn)品中形成一定的結(jié)構(gòu)，然后靠升華和解吸附作用將溶劑的量減少至不足以維持生物生長和發(fā)生化學(xué)反應(yīng)的程度。,BasicDifference基本差別,Lyophilizationproductremainsfrozenduringthedryingprocess凍干-干燥過程中產(chǎn)品保持冷凍FreezeDryingproductmaynotremainfrozenduringthedryingprocess冷凍干燥-凍干過程中產(chǎn)品可能不是冷凍狀態(tài)Keypointisthetermfrozen“凍干”這個(gè)詞是關(guān)鍵點(diǎn),MostImportantStep最重要的步驟,Formulation配方,WhyistheFormulationsoImportant?為何配方如此重要,Definesthefreezingprocess限定冷凍過程Definesthedryingprocessparameters限定干燥過程參數(shù)Definesthefreezedryingequipmentrequirements限定冷凍干燥設(shè)備要求Definestheshelf-lifeoftheproduct限定產(chǎn)品的貨架壽命Definesiftheprocessisgoingtobelyophilizedorfreezedried限定產(chǎn)品是凍干還是冷凍干燥,KeyPropertiesoftheFormulation配方的關(guān)鍵性質(zhì),Composition組成Stability穩(wěn)定性ThermalProperties熱性質(zhì),KeyThermalProperties主要的熱性質(zhì),DegreeofSupercooling過冷度EutecticorCollapseTemperature共晶或塌陷溫度DegreeofCrystallization結(jié)晶度,Supercooling過冷度,Thedegreeofsupercoolingisdefinedasthenumberofdegreesbelowtheequilibriumfreezingtemperaturewhereicefirststartstoform.過冷度是指低于冰開始形成時(shí)的冷凍平衡溫度的度數(shù),KeyThermalProperties主要的熱性質(zhì),DegreeofSupercooling過冷度EutecticorCollapseTemperature共晶或塌陷溫度DegreeofCrystallization結(jié)晶度,BasicDefinitionofaEutectic共晶點(diǎn)的基本定義,Thattemperatureatwhichthenumberofdegreesoffreedominasystemduringfreezingiszero.(f=0)冷凍過程中，該溫度下系統(tǒng)的自由度為零Thepointofintersectionbetweenthesolubilitycurveforasaturatedsolutionandthedepressionofthefreezingpointofthesolvent飽和溶液的溶解曲線和溶劑結(jié)冰點(diǎn)凹陷的交點(diǎn),KeyThermalProperties主要熱性質(zhì),DegreeofSupercooling過冷度EutecticorCollapseTemperature共晶和塌陷溫度DegreeofCrystallization結(jié)晶度,CollapseTemperature塌陷溫度,Thecollapsetemperatureisdefinedasthattemperatureatwhichthemobilityofthewaterintheinterstitialregionapproacheszero.塌陷溫度是指脈間區(qū)的水的流動性為零時(shí)溫度,KeyThermalProperties主要熱性質(zhì),DegreeofSupercooling過冷度EutecticorCollapseTemperature共晶或塌陷溫度DegreeofCrystallization結(jié)晶度,DegreeofCrystallization結(jié)晶度,Thedegreeofcrystallizationistheratiooftheiceformedintheproducttotheamountoficeformedinanequalamountofwater.結(jié)晶度是指產(chǎn)品中形成的冰的量和等量水形成的冰的量的比率,KeyProcessSteps主要工藝步驟,Freezing冷凍,WhattoconsiderbeforetheFreezingProcess冷凍開始前需要考慮的因素,Stabilityoftheliquidformulation液體配方的穩(wěn)定性Moldedvial,tubingvialortray模制西林瓶，管制西林瓶或托盤Dimensionsandcompositionofthecontainer容器的尺寸和成分Fillvolumeandaspectratio(w/h)1裝料體積和長寬比（w/h）1,WhattoconsiderfortheFreezingProcess冷凍過程中需要考慮的問題,Initialshelfsurfacetemperature(formulation,fillvolume,stability)擱板表面的初始溫度（配方，裝料體積，穩(wěn)定性）Initialshelfsurfacetemperature(ambient,4-8oC,0oC)擱板表面的初始溫度（室溫，4-8oC,100mTorr以阻止氣體回流,ExampleofPrimaryDrying第一次干燥舉例,Tc=-23oCTp=-28oCPp=340mTorrPc=100mTorrTi=-40oCTs=10oC?(TpTi)=12oC,KeyProcessSteps主要凍干步驟,Freezing冷凍PrimaryDrying第一次干燥SecondaryDrying第二次干燥,SecondaryDrying第二次干燥,Dependentonadsorptionisotherms(formulationandcakestructure)取決于吸收溫度曲線（配方和餅狀物結(jié)構(gòu)）Keyparameterspartialpressureofwatervaporinthevial(Pw)andTp主要參數(shù)西林瓶中蒸氣分壓,ExampleofSecondaryDrying第二次干燥的例子,ShelftemperaturerampTsTp10oC擱板溫度斜面TsTp10oCHowlongwhenTp=Ts?達(dá)到Tp=Ts時(shí)要多長時(shí)間？,EndofSecondaryDrying第二次干燥的終點(diǎn),FinalProductProperties最重產(chǎn)品性質(zhì),Cosmetic化妝品,FinalProductProperties最重產(chǎn)品性質(zhì),Cosmetic化妝品Reconsitution復(fù)水,Reconstitution復(fù)水,Timelessthan3minutes時(shí)間-不超過3分鐘Checkassayoftheformulation配方的檢查化驗(yàn)CheckthepHpH的檢查Checkforturbidity混濁度的檢查,FinalProductProperties最終產(chǎn)品的性質(zhì),Cosmetic化妝品Reconstitution復(fù)水Moisture水分,Moisture水分,MethodKarlFischerorLossonDrying(productdependent)方法-KarlFischer法或失重法（依產(chǎn)品而定）Establishtheacceptablerangeofmoisturevalues(basedonstability)建立可接受的水分值范圍（根據(jù)穩(wěn)定性）Howmanysamples?有多少樣品？,FinalProductProperties最終產(chǎn)品性質(zhì),Cosmetic化妝品Reconstitution復(fù)水Moisture水分Stability穩(wěn)定性,SummaryforOptimization關(guān)于優(yōu)化的小結(jié),Formulation(mostimportant)配方（很重要）Thermalproperties(musthave)熱性質(zhì)（必須有）Freezing(formulation,t