Freeze-Dryer Equipment Capability Limit: Comparison of Computational Modeling With Experiments at Laboratory Scale
Freeze-Dryer Equipment Capability Limit: Comparison of Computational Modeling With Experiments at Laboratory Scale
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DOI：
10.1016/j.xphs.2019.04.016
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发表时间：
2019-09-01
影响因子：
3.8
通讯作者：
Alexeenko, Alina A.
中科院分区：
文献类型：
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作者：
Shivkumar, Gayathri;Kshirsagar, Vaibhav;Alexeenko, Alina A.
设备性能曲线是冷冻干燥设计空间的边界元素之一，理解它对工艺设计、转移和放大至关重要。设计空间的第二个边界元素是产品温度极限，超过该极限产品就会崩溃。与冷冻干燥任何产品相关的高成本使得在设备和产品的限制内使用最有效的循环进行操作至关重要。在这项工作中，我们提出了一个计算模型来生成2个实验室规模的冷冻干燥机的设备性能曲线，并将结果与实验生成的设备性能曲线进行了比较。模拟结果与实验结果的平均偏差分别为-4.8%和-7.2%。此外，我们还研究了各种数值和几何参数对模拟设备性能的影响。在数值参数中，壁面热边界条件的影响最大，最大值为12.3%。在几何参数中，隔离阀的加入使设备性能降低了23.7%。控制成核技术需要较大的隔离阀，以较低的升华速率阻塞管道中的流动，从而降低设备的能力极限。(c) 2019年由爱思唯尔公司代表美国药剂师协会出版。
The equipment capability curve is one of the bounding elements of the freeze-drying design space, and understanding it is critical to process design, transfer, and scale-up. The second bounding element of the design space is the product temperature limit beyond which the product collapses. The high cost associated with freeze-drying any product renders it crucial to operate using the most efficient cycle within the limits of the equipment and the product. In this work, we present a computational model to generate the equipment capability curve for 2 laboratory scale freeze-dryers and compare the results to experimentally generated equipment capability curves. The average deviations of the modeling results from the experiments for the 2 lyophilizers modeled are -4.8% and -7.2%. In addition, we investigate the effect of various numerical and geometric parameters on the simulated equipment capability. Among the numerical parameters, the chamber wall thermal boundary conditions exert the largest influence with a maximum value of 12.3%. Among the geometric parameters, the inclusion of the isolation valve reduces the equipment capability by 23.7%. Larger isolation valves, required for controlled nucleation technology, choke the flow in the duct at lower sublimation rates, thereby lowering the equipment capability limit. (c) 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.