School of Aeronautics and Astronautics, Purdue University, West Lafayette, Indiana 47907.
Pfizer Biotherapeutics R&D, Andover, Massachusetts 01810.
J Pharm Sci. 2019 Jan;108(1):382-390. doi: 10.1016/j.xphs.2018.10.061. Epub 2018 Nov 8.
Equipment capability is an important factor in scale up and technology transfer for lyophilized pharmaceutical products. Experimental determination of equipment capability limits, such as the maximum sublimation rate at a given chamber pressure, is time-intensive for production lyophilizers. Here, we present computational fluid dynamics modeling of equipment capability and compare it with experimental data for minimum controllable pressure ice slab sublimation tests in a 23 m shelf area freeze dryer. It is found that the vapor flow in the production scale is characterized by turbulent effects at high sublimation rates. For the considered freeze dryer configuration, the onset of turbulence occurs at a sublimation rate of 17 kg/h and leads to an increase in the minimum controllable pressure by 3-4 mTorr for the flow rates up to 40 kg/h. Variations in the shelf and duct orientations as well as the valve stroke distance and their effect on the equipment limit and pressure uniformity are also discussed. The minimum controllable pressure measured experimentally agreed within 5% with computational fluid dynamics results. For high vapor sublimation rates at final stages of ice slab testing, the condenser load affects the product chamber pressure control. Estimate of condenser pressure changes because of ice accumulation has been included.
设备性能是冻干药品放大和技术转移的一个重要因素。对于生产型冻干机，实验确定设备性能极限（例如在给定腔室压力下的最大升华速率）是一项耗时的工作。在这里，我们对设备性能进行了计算流体动力学建模，并将其与在 23 平方米搁板面积的冷冻干燥器中进行的最小可控压力冰板升华测试的实验数据进行了比较。结果发现，在高升华速率下，生产规模中的蒸汽流表现出湍流效应。对于所考虑的冷冻干燥器配置，在升华速率为 17kg/h 时出现湍流，并且对于高达 40kg/h 的流速，最小可控压力增加了 3-4mTorr。还讨论了搁板和管道方向的变化以及阀行程距离及其对设备极限和压力均匀性的影响。实验测量的最小可控压力与计算流体动力学结果的偏差在 5%以内。在冰板测试的最后阶段，高蒸汽升华速率会影响产品腔室压力控制。由于冰积累导致的冷凝器压力变化的估计已包括在内。
