冻干工艺的优化.ppt

1、a,1,Optimization of the Lyophilization or Freeze Drying Process 冻干工艺的优化,a,2,Definition of Lyophilization 冻干的定义,A stabilizing process in which the product is first frozen and then the amount of solvent is removed first by sublimation and then by desorption to values that will no longer support biolog

2、ical growth or chemical reactions. 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,a,3,Definition of Freeze Drying 冷冻干燥的定义,Freeze drying is a stabilizing process in which there is first crystallization of the solvent to form a structure in the product and then the amount of s

3、olvent is removed first by sublimation and then by desorption to values that will no longer support biological growth or chemical reactions. 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。,a,4,Basic Difference 基本差别,Lyophilization product remains frozen during the d

4、rying process 冻干-干燥过程中产品保持冷冻 Freeze Drying product may not remain frozen during the drying process 冷冻干燥-冻干过程中产品可能不是冷冻状态 Key point is the term frozen “冻干”这个词是关键点,a,5,Most Important Step 最重要的步骤,Formulation 配方,a,6,Why is the Formulation so Important? 为何配方如此重要,Defines the freezing process 限定冷冻过程 Defines

5、 the drying process parameters限定干燥过程参数 Defines the freeze drying equipment requirements 限定冷冻干燥设备要求 Defines the shelf-life of the product 限定产品的货架寿命 Defines if the process is going to be lyophilized or freeze dried 限定产品是冻干还是冷冻干燥,a,7,Key Properties of the Formulation 配方的关键性质,Composition 组成 Stability 稳定

6、性 Thermal Properties热性质,a,8,Key Thermal Properties 主要的热性质,Degree of Supercooling 过冷度 Eutectic or Collapse Temperature 共晶或塌陷温度 Degree of Crystallization 结晶度,a,9,Supercooling 过冷度,The degree of supercooling is defined as the number of degrees below the equilibrium freezing temperature where ice first s

7、tarts to form. 过冷度是指低于冰开始形成时的冷冻平衡温度的度数,a,10,a,11,Key Thermal Properties 主要的热性质,Degree of Supercooling 过冷度 Eutectic or Collapse Temperature 共晶或塌陷温度 Degree of Crystallization 结晶度,a,12,Basic Definition of a Eutectic 共晶点的基本定义,That temperature at which the number of degrees of freedom in a system during

8、freezing is zero. (f = 0) 冷冻过程中，该温度下系统的自由度为零 The point of intersection between the solubility curve for a saturated solution and the depression of the freezing point of the solvent 饱和溶液的溶解曲线和溶剂结冰点凹陷的交点,a,13,a,14,Key Thermal Properties 主要热性质,Degree of Supercooling 过冷度 Eutectic or Collapse Temperature

9、 共晶和塌陷温度 Degree of Crystallization 结晶度,a,15,Collapse Temperature 塌陷温度,The collapse temperature is defined as that temperature at which the mobility of the water in the interstitial region approaches zero. 塌陷温度是指脉间区的水的流动性为零时温度,a,16,a,17,Key Thermal Properties 主要热性质,Degree of Supercooling 过冷度 Eutectic

10、 or Collapse Temperature 共晶或塌陷温度 Degree of Crystallization 结晶度,a,18,Degree of Crystallization 结晶度,The degree of crystallization is the ratio of the ice formed in the product to the amount of ice formed in an equal amount of water. 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,a,19,a,20,Key Process Steps 主要工艺步骤,Freezi

11、ng 冷冻,a,21,What to consider before the Freezing Process 冷冻开始前需要考虑的因素,Stability of the liquid formulation 液体配方的稳定性 Molded vial, tubing vial or tray 模制西林瓶，管制西林瓶或托盘 Dimensions and composition of the container 容器的尺寸和成分 Fill volume and aspect ratio (w/h) 1 装料体积和长宽比（w/h）1,a,22,What to consider for the Fre

12、ezing Process 冷冻过程中需要考虑的问题,Initial shelf surface temperature (formulation, fill volume, stability) 搁板表面的初始温度（配方，装料体积，稳定性） Initial shelf surface temperature (ambient, 4 - 8 oC, 0 oC) 搁板表面的初始温度（室温，4 - 8 oC, 100 mTorr以阻止气体回流,a,30,Example of Primary Drying 第一次干燥举例,Tc = - 23 oC Tp = -28 oC Pp = 340 mTorr

13、 Pc = 100 mTorr Ti = - 40 oC Ts = 10 oC ? (Tp Ti) = 12 oC,a,31,Key Process Steps 主要冻干步骤,Freezing 冷冻 Primary Drying 第一次干燥 Secondary Drying 第二次干燥,a,32,Secondary Drying 第二次干燥,Dependent on adsorption isotherms (formulation and cake structure) 取决于吸收温度曲线（配方和饼状物结构） Key parameters partial pressure of water

14、vapor in the vial (Pw ) and Tp 主要参数西林瓶中蒸气分压,a,33,Example of Secondary Drying 第二次干燥的例子,Shelf temperature ramp Ts Tp 10 oC 搁板温度斜面Ts Tp 10 oC How long when Tp = Ts ? 达到Tp = Ts时要多长时间？,a,34,End of Secondary Drying 第二次干燥的终点,a,35,Final Product Properties 最重产品性质,Cosmetic 化妆品,a,36,a,37,Final Product Properti

15、es 最重产品性质,Cosmetic 化妆品 Reconsitution 复水,a,38,Reconstitution 复水,Time less than 3 minutes 时间-不超过3分钟 Check assay of the formulation 配方的检查化验 Check the pH pH的检查 Check for turbidity 混浊度的检查,a,39,Final Product Properties 最终产品的性质,Cosmetic 化妆品 Reconstitution 复水 Moisture 水分,a,40,Moisture 水分,Method Karl Fischer

16、 or Loss on Drying (product dependent) 方法-Karl Fischer 法或失重法（依产品而定） Establish the acceptable range of moisture values (based on stability) 建立可接受的水分值范围（根据稳定性） How many samples? 有多少样品？,a,41,Final Product Properties 最终产品性质,Cosmetic化妆品 Reconstitution复水 Moisture水分 Stability稳定性,a,42,Summary for Optimization 关于优化的小结,Formulation (most important ) 配方（很重要） Thermal properties (must have) 热性质（必须有） Freezing (