Correlation of laboratory and production freeze drying cycles
Correlation of laboratory and production freeze drying cycles
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DOI：
10.1016/j.ijpharm.2005.06.022
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发表时间：
2005-09-30
影响因子：
5.8
通讯作者：
Akers, MJ
中科院分区：
文献类型：
--
作者：
Kuu, WY;Hardwick, LA;Akers, MJ
本研究的目的是开发实验室和生产冷冻干燥机之间循环参数的相关性。通过建立的相关性，使用实验室干燥机获得的关键循环参数可以通过最少的实验工作转换为生产干燥机的参数。为了建立相关性，重要的是要考虑以下冷冻干燥组件的贡献：（1）干燥器，（2）小瓶，以及（3）配方。干燥机的关键参数是搁板传热系数和搁板表面辐射发射率。小瓶的关键参数是小瓶底部传热系数（接触参数 K-cs 和间隔距离 l(v)）和小瓶顶部传热系数。配方的关键参数是干层传质系数。上述传热传质系数是通过冷冻干燥实验结合数学模型确定的。根据获得的传热和传质系数，使用初级干燥子程序模拟初级干燥期间的最高产品温度 T-bmax，作为搁板温度和室压力的函数。然后根据 T-bmax 的结果值模拟所需的搁板温度和腔室压力，以成功执行循环运行而不会导致产品塌陷。通过模型配方 5% 甘露醇溶液的初步干燥证明了所建立的相关方法。使用LyoStar (TM) 干燥器作为实验室干燥器和BOC Edwards (TM) 干燥器作为生产干燥器进行循环运行。测定的 5% 甘露醇标准化干层传质阻力表示为 R-pN = 0.7313 + 17.19l，其中 e 是后退干层厚度。使用模型配方 5% 甘露醇演示相关方法后，对实际产品乳酸脱氢酶 (LDH) 配方进行了实际比较研究。测定的 LDH 配方的归一化干燥层传质阻力表示为 R-pN = 4.344 + 10.85l。操作模板 T-bmax 和初级干燥时间也是通过模拟生成的。使用 Edwards (TM) 生产干燥机进行 LDH 配方的循环运行验证了在实验室冷冻干燥机中开发的循环可以在生产规模上转移。 (c) 2005 Elsevier B.V. 保留所有权利。
The purpose of this study was to develop the correlation of cycle parameters between a laboratory and a production freeze-dryer. With the established correlation, key cycle parameters obtained using a laboratory dryer may be converted to those for a production dryer with minimal experimental efforts. In order to develop the correlation, it was important to consider the contributions from the following freeze-drying components: (1) the dryer, (2) the vial, and (3) the formulation. The critical parameters for the dryer are the shelf heat transfer coefficient and shelf surface radiation emissivity. The critical parameters for the vial are the vial bottom heat transfer coefficients (the contact parameter K-cs and separation distance l(v)), and vial top heat transfer coefficient. The critical parameter of the formulation is the dry layer mass transfer coefficient. The above heat and mass transfer coefficients were determined by freeze-drying experiments in conjunction with mathematical modeling. With the obtained heat and mass transfer coefficients, the maximum product temperature, T-bmax, during primary drying was simulated using a primary drying subroutine as a function of the shelf temperature and chamber pressure. The required shelf temperature and chamber pressure, in order to perform a successful cycle run without product collapse, were then simulated based on the resulting values of T-bmax. The established correlation approach was demonstrated by the primary drying of the model formulation 5% mannitol solution. The cycle runs were performed using a LyoStar (TM) dryer as the laboratory dryer and a BOC Edwards (TM) dryer as the production dryer. The determined normalized dried layer mass transfer resistance for 5% mannitol is expressed as R-pN = 0.7313 + 17.19l, where e is the receding dry layer thickness. After demonstrating the correlation approach using the model formulation 5% mannitol, a practical comparison study was performed for the actual product, the lactate dehydrogenase (LDH) formulation. The determined normalized dried layer mass transfer resistance for the LDH formulation is expressed as R-pN = 4.344 + 10.85l. The operational templates T-bmax and primary drying time were also generated by simulation. The cycle run for the LDH formulation using the Edwards (TM) production dryer verified that the cycle developed in a laboratory freeze-dryer was transferable at the production scale. (c) 2005 Elsevier B.V. All rights reserved.