School of Aeronautics and Astronautics, Purdue University, West Lafayette, Indiana 47907.
Baxter BioPharma Solutions LLC, Bloomington, Indiana 47403.
J Pharm Sci. 2019 Sep;108(9):2972-2981. doi: 10.1016/j.xphs.2019.04.016. Epub 2019 Apr 18.
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.
设备能力曲线是冻干设计空间的边界要素之一，理解它对于工艺设计、转移和放大至关重要。设计空间的第二个边界要素是产品温度限制，超过该限制产品会崩溃。由于任何产品的冻干成本都很高，因此在设备和产品的限制范围内使用最有效的循环来操作非常关键。在这项工作中，我们提出了一种计算模型来生成 2 台实验室规模冻干机的设备能力曲线，并将结果与实验生成的设备能力曲线进行比较。模拟结果与所模拟的 2 台冻干机的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能力的影响。在数值参数中，腔壁热边界条件的影响最大，最大值为 12.3%。在几何参数中，隔离阀的包含将设备能力降低了 23.7%。为了实现控制成核技术，需要更大的隔离阀，这会在较低的升华速率下阻塞管道中的流量，从而降低设备能力极限。
