冻干工艺的优化

Copyright2006PhaseTechnologies,IncOptimizationoftheLyophilizationorFreezeDryingProcess冻干工艺的优化Copyright2006PhaseTechnologies,IncDefinitionofLyophilization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Copyright2006PhaseTechnologies,IncDefinitionofFreezeDrying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。Copyright2006PhaseTechnologies,IncBasicDifference基本差别Lyophilization–productremainsfrozenduringthedryingprocess冻干-干燥过程中产品保持冷冻FreezeDrying–productmaynotremainfrozenduringthedryingprocess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Copyright2006PhaseTechnologies,IncMostImportantStep最重要的步骤Formulation配方Copyright2006PhaseTechnologies,IncWhyistheFormulationsoImportant?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Copyright2006PhaseTechnologies,IncKeyPropertiesoftheFormulation配方的关键性质Composition组成Stability稳定性ThermalProperties热性质Copyright2006PhaseTechnologies,IncKeyThermalProperties主要的热性质DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶或塌陷温度DegreeofCrystallization结晶度Copyright2006PhaseTechnologies,IncSupercooling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Copyright2006PhaseTechnologies,IncCopyright2006PhaseTechnologies,IncKeyThermalProperties主要的热性质DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶或塌陷温度DegreeofCrystallization结晶度Copyright2006PhaseTechnologies,IncBasicDefinitionofaEutectic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Copyright2006PhaseTechnologies,IncCopyright2006PhaseTechnologies,IncKeyThermalProperties主要热性质DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶和塌陷温度DegreeofCrystallization结晶度Copyright2006PhaseTechnologies,IncCollapseTemperature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Copyright2006PhaseTechnologies,IncCopyright2006PhaseTechnologies,IncKeyThermalProperties主要热性质DegreeofSupercooling过冷度EutecticorCollapseTemperature共晶或塌陷温度DegreeofCrystallization结晶度Copyright2006PhaseTechnologies,IncDegreeofCrystallization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Copyright2006PhaseTechnologies,IncCopyright2006PhaseTechnologies,IncKeyProcessSteps主要工艺步骤Freezing冷冻Copyright2006PhaseTechnologies,IncWhattoconsiderbeforetheFreezingProcess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）1Copyright2006PhaseTechnologies,IncWhattoconsiderfortheFreezingProcess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,0oC)Shelfcoolingrate(supercoolingandfillvolume)搁板冷却速率（过冷河装料体积）Freezingtemperature(eutecticorcollapsetemperature10oClower–mobilityofwateriszero)冷冻温度（共晶和塌陷温度10oC更低-水的移动性为零Time(fillvolume)/时间（装料体积）Copyright2006PhaseTechnologies,IncEffectofFreezingontheProduct冷冻对产品的影响Wasthereachangeinthecompositionoftheformulation?/配方的成分时候有变化Anychangeinturbidity?/混浊度是否有变化Natureofthefrozencake(uniformorcrustorglaze)冷冻饼状物的性质（均一或者硬壳或冻胶层）Copyright2006PhaseTechnologies,IncExampleofaFreezingProcess冻干过程举例DegreeofSupercooling=7oC过冷度=7oCCollapsetemperature(Tc)=-23oC塌陷温度=-23oCFreezingtemperature–35oC冷冻温度–35oCCopyright2006PhaseTechnologies,IncKeyProcessSteps主要工艺步骤Freezing冷冻PrimaryDrying第一次干燥Copyright2006PhaseTechnologies,IncPrimaryDrying第一次干燥Sublimationoficefromthematrixaccordingtothephasediagramofwater根据水的相图使水从基质中升华Lyophilization–frozeninterstitial冻干-脉间区冻结FreezeDrying–frozenornotfrozeninterstitialregion.冷冻干燥-脉间区冻结或不冻结Copyright2006PhaseTechnologies,IncKeyPrimaryDryingParameters第一次干燥主要参数PcTsTpPc=Chamberpressure/箱内压力Ts=Shelfsurfacetemperature/搁板表面温度Tp=Producttemperature/产品温度Copyright2006PhaseTechnologies,IncSelecttheChamberPressure选择箱内压力Determinethevaporpressureoficeat5oCbelowthecollapseoreutectictemperature在低于塌陷温度或共晶点5oC的温度下确定冰的蒸气压Copyright2