Vallan Alberto, Fissore Davide, Pisano Roberto, Barresi Antonello A
Department of Electronics and Telecommunications, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy.
Department of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy.
Pharmaceutics. 2023 Mar 7;15(3):861. doi: 10.3390/pharmaceutics15030861.
The measurement of product temperature is one of the methods that can be adopted, especially in the pharmaceutical industry, to monitor the freeze-drying process and to obtain the values of the process parameters required by mathematical models useful for in-line (or off-line) optimization. Either a contact or a contactless device and a simple algorithm based on a mathematical model of the process can be employed to obtain a PAT tool. This work deeply investigated the use of direct temperature measurement for process monitoring to determine not only the product temperature, but also the end of primary drying and the process parameters (heat and mass transfer coefficients), as well as evaluating the degree of uncertainty of the obtained results. Experiments were carried out with thin thermocouples in a lab-scale freeze-dryer using two different model products, sucrose and PVP solutions; they are representative of two types of commonly freeze-dried products, namely those whose structures are strongly nonuniform in the axial direction, showing a variable pore size with the cake depth and a crust (leading to a strongly nonlinear cake resistance), as well as those whose structures are uniform, with an open structure and, consequently, a cake resistance varying linearly with thickness. The results confirm that the model parameters in both cases can be estimated with an uncertainty that is in agreement with that obtained with other more invasive and expensive sensors. Finally, the strengths and weaknesses of the proposed approach coupled with the use of thermocouples was discussed, comparing with a case using a contactless device (infrared camera).
测量产品温度是可采用的方法之一，尤其在制药行业，用于监测冷冻干燥过程并获取数学模型所需的过程参数值，这些模型对在线（或离线）优化很有用。可以使用接触式或非接触式设备以及基于过程数学模型的简单算法来获得一个过程分析技术（PAT）工具。这项工作深入研究了使用直接温度测量进行过程监测，不仅要确定产品温度，还要确定一次干燥的结束以及过程参数（传热和传质系数），同时评估所得结果的不确定度。实验是在实验室规模的冷冻干燥机中使用两种不同的模型产品蔗糖和聚乙烯吡咯烷酮（PVP）溶液，通过细热电偶进行的；它们代表了两种常见的冷冻干燥产品类型，一种是轴向结构强烈不均匀，孔径随饼层深度变化且有外皮（导致饼层阻力强烈非线性）的产品，另一种是结构均匀、具有开放结构且饼层阻力随厚度线性变化的产品。结果证实，在这两种情况下，模型参数都可以在与其他更具侵入性且昂贵的传感器所获得的不确定度一致的情况下进行估计。最后，讨论了所提出的结合使用热电偶的方法的优缺点，并与使用非接触式设备（红外热像仪）的情况进行了比较。
