Wireless sensor networks for pharmaceutical lyophilization: Quantification of local gas pressure and temperature in primary drying
Wireless sensor networks for pharmaceutical lyophilization: Quantification of local gas pressure and temperature in primary drying
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DOI：
10.1016/j.ejpb.2021.09.005
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发表时间：
2021-09-24
影响因子：
4.9
通讯作者：
Alexeenko, Alina
中科院分区：
文献类型：
--
作者：
Strongrich, Andrew;Alexeenko, Alina
无线传感器网络在广泛的工业过程中已经变得多产，并且在定位灵活性、模块化、互连性和数据路由方面提供了优于有线传感器网络的几个关键优势。我们展示了它们在药物冻干中的实用性，通过开发一系列无线设备来测量初级干燥过程中气体压力和温度的空间变化。使用实验室规模的药物冻干机，探索搁板温度、室压、辅料浓度和干燥器配置对各种代表性循环的影响。在这些情况下，整个大陆架的压力和温度变化分别高达1.2 Pa和10 ℃。计算流体动力学模拟支持实验测量，以揭示驱动蒸汽流动的机制。然后将测量和模拟数据组合以基于与重量分析数据的比较在相反意义上估计货架升华速率，偏差在3%以内。然后，我们应用升华速率曲线获得5% w/v甘露醇制剂的小瓶传热系数和产品传质阻力。最后，将这些参数应用于一维准稳态传热模型，以预测初级干燥过程中产品温度的演变。热电偶测量的产品温度进行比较，直接模拟的数据，并证明精度与现有的一维模型。
Wireless sensor networks have become prolific in a wide range of industrial processes and offer several key advantages over their wired counterparts in terms of positioning flexibility, modularity, interconnectivity, and data routing. We demonstrate their utility in pharmaceutical lyophilization by developing a series of wireless devices to measure spatial variations in gas pressure and temperature during primary drying. The influence of shelf temperature, chamber pressure, excipient concentration, and dryer configuration are explored for various representative cycles using a laboratory-scale pharmaceutical lyophilizer. Pressure and temperature variations across the shelf for these cases are shown to vary up to 1.2 Pa and 10 degrees C, respectively. Experimental measurements are supported by computational fluid dynamics simulations to reveal the mechanisms driving the vapor flow. The measurements and simulation data are then combined to estimate the shelf-wise sublimation rate in the inverse sense to within a deviation of 3% based on comparison with gravimetric data. We then apply the sublimation rate profile to obtain the vial heat transfer coefficient and product mass transfer resistance for a 5% w/v mannitol formulation. Finally, these parameters are applied to a one-dimensional quasi-steady heat transfer model to predict the evolution of the product temperature over the course of primary drying. Thermocouple measurements of product temperature are compared directly to the simulated data and demonstrate accuracy comparable to existing published one-dimensional models.