冻干工艺的优化

.,OptimizationoftheLyophilizationorFreezeDryingProcess冻干工艺的优化,.,DefinitionofLyophilization冻干的定义,Astabilizingprocessinwhichtheproductisfirstfrozenandthentheamountofsolventisremovedfirstbysublimationandthenbydesorptiontovaluesthatwillnolongersupportbiologicalgrowthorchemicalreactions.冻干是一个使物质稳定化的过程，在该过程中，首先使产品冷冻，然后将溶剂升华和解吸附，使产品中的含水量减少到不足以支持生物生长和发生化学反应的程度,.,DefinitionofFreezeDrying冷冻干燥的定义,Freezedryingisastabilizingprocessinwhichthereisfirstcrystallizationofthesolventtoformastructureintheproductandthentheamountofsolventisremovedfirstbysublimationandthenbydesorptiontovaluesthatwillnolongersupportbiologicalgrowthorchemicalreactions.冷冻干燥是一个是物质稳定的过程，在该过程中，冻干的溶剂先结晶，在产品中形成一定的结构，然后靠升华和解吸附作用将溶剂的量减少至不足以维持生物生长和发生化学反应的程度。,.,BasicDifference基本差别,Lyophilizationproductremainsfrozenduringthedryingprocess冻干-干燥过程中产品保持冷冻FreezeDryingproductmaynotremainfrozenduringthedryingprocess冷冻干燥-冻干过程中产品可能不是冷冻状态Keypointisthetermfrozen“冻干”这个词是关键点,.,MostImportantStep最重要的步骤,Formulation配方,.,WhyistheFormulationsoImportant?为何配方如此重要,Definesthefreezingprocess限定冷冻过程Definesthedryingprocessparameters限定干燥过程参数Definesthefreezedryingequipmentrequirements限定冷冻干燥设备要求Definestheshelf-lifeoftheproduct限定产品的货架寿命Definesiftheprocessisgoingtobelyophilizedorfreezedried限定产品是冻干还是冷冻干燥,.,KeyPropertiesoftheFormulation配方的关键性质,Composition组成Stability稳定性ThermalProperties热性质,.,KeyThermalProperties主要的热性质,DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶或塌陷温度DegreeofCrystallization结晶度,.,Supercooling过冷度,Thedegreeofsupercoolingisdefinedasthenumberofdegreesbelowtheequilibriumfreezingtemperaturewhereicefirststartstoform.过冷度是指低于冰开始形成时的冷冻平衡温度的度数,.,.,KeyThermalProperties主要的热性质,DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶或塌陷温度DegreeofCrystallization结晶度,.,BasicDefinitionofaEutectic共晶点的基本定义,Thattemperatureatwhichthenumberofdegreesoffreedominasystemduringfreezingiszero.(f=0)冷冻过程中，该温度下系统的自由度为零Thepointofintersectionbetweenthesolubilitycurveforasaturatedsolutionandthedepressionofthefreezingpointofthesolvent饱和溶液的溶解曲线和溶剂结冰点凹陷的交点,.,.,KeyThermalProperties主要热性质,DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶和塌陷温度DegreeofCrystallization结晶度,.,CollapseTemperature塌陷温度,Thecollapsetemperatureisdefinedasthattemperatureatwhichthemobilityofthewaterintheinterstitialregionapproacheszero.塌陷温度是指脉间区的水的流动性为零时温度,.,.,KeyThermalProperties主要热性质,DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶或塌陷温度DegreeofCrystallization结晶度,.,DegreeofCrystallization结晶度,Thedegreeofcrystallizationistheratiooftheiceformedintheproducttotheamountoficeformedinanequalamountofwater.结晶度是指产品中形成的冰的量和等量水形成的冰的量的比率,.,.,KeyProcessSteps主要工艺步骤,Freezing冷冻,.,WhattoconsiderbeforetheFreezingProcess冷冻开始前需要考虑的因素,Stabilityoftheliquidformulation液体配方的稳定性Moldedvial,tubingvialortray模制西林瓶，管制西林瓶或托盘Dimensionsandcompositionofthecontainer容器的尺寸和成分Fillvolumeandaspectratio(w/h)1装料体积和长宽比（w/h）1,.,WhattoconsiderfortheFreezingProcess冷冻过程中需要考虑的问题,Initialshelfsurfacetemperature(formulation,fillvolume,stability)搁板表面的初始温度（配方，装料体积，稳定性）Initialshelfsurfacetemperature(ambient,4-8oC,0oC)搁板表面的初始温度（室温，4-8oC,100mTorr以阻止气体回流,.,ExampleofPrimaryDrying第一次干燥举例,Tc=-23oCTp=-28oCPp=340mTorrPc=100mTorrTi=-40oCTs=10oC?(TpTi)=12oC,.,KeyProcessSteps主要冻干步骤,Freezing冷冻PrimaryDrying第一次干燥SecondaryDrying第二次干燥,.,SecondaryDrying第二次干燥,Dependentonadsorptionisotherms(formulationandcakestructure)取决于吸收温度曲线（配方和饼状物结构）Keyparameterspartialpressureofwatervaporinthevial(Pw)andTp主要参数西林瓶中蒸气分压,.,ExampleofSecondaryDrying第二次干燥的例子,ShelftemperaturerampTsTp10oC搁板温度斜面TsTp10oCHowlongwhenTp=Ts?达到Tp=Ts时要多长时间？,.,EndofSecondaryDrying第二次干燥的终点,.,FinalProductProperties最重产品性质,Cosmetic化妆品,.,.,FinalProductProperties最重产品性质,Cosmetic化妆品Reconsitution复水,.,Reconstitution复水,Timelessthan3minutes时间-不超过3分钟Checkassayoftheformulation配方的检查化验CheckthepHpH的检查Checkforturbidity混浊度的检查,.,FinalProductProperties最终产品的性质,Cosmetic化妆品Reconstitution复水Moisture水分,.,Moisture水分,MethodKarlFischerorLossonDrying(productdependent)方法-KarlFischer法或失重法（依产品而定）Establishtheacceptablerangeofmoisturevalues(basedonstability)建立可接受的水分值范围（根据稳定性）Howmanysamples?有多少样品？,.,FinalProductProperties最终产品性质,Cosmetic化妆品Reconstitution复水Moisture水分Stability稳定性,.,SummaryforOptimization关于优化的小结,Formulation(mostimportant)配方（很重要）Thermalproperties(musthave)热性质（必须有）Freezing(formulatio