Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
Eur J Pharm Biopharm. 2018 Jun;127:159-170. doi: 10.1016/j.ejpb.2018.02.025. Epub 2018 Feb 21.
The continuous freeze-drying concept based on spinning the vials during freezing and on non-contact energy transfer via infrared (IR) radiation during drying, improves process efficiency and product quality (uniformity) compared to conventional batch freeze-drying. Automated control of this process requires the fundamental mechanistic modelling of each individual process step. Therefore, a framework is presented for the modelling and control of the continuous primary drying step based on non-contact IR radiation. The IR radiation emitted by the radiator filaments passes through various materials before finally reaching the spin frozen vial. The energy transfer was computed by combining physical laws with Monte Carlo simulations and was verified with experimental data. The influence of the transmission properties of various materials on the emitted IR radiation profile was evaluated. These results assist in the selection of proper materials which could serve as IR window in the continuous freeze-drying prototype. The modelling framework presented in this paper fits the model-based design approach used for the development of this prototype and shows the potential benefits of this design strategy by establishing the desired engineering parameters and by enabling the engineer to assess mechanical tolerances and material options.
基于旋转瓶冷冻和非接触式红外（IR）辐射干燥过程中的能量传递的连续冷冻干燥概念，与传统的批量冷冻干燥相比，提高了工艺效率和产品质量（均匀性）。该过程的自动化控制需要对每个单独的工艺步骤进行基本的机理建模。因此，提出了一种基于非接触式 IR 辐射的连续初级干燥步骤建模和控制框架。散热器灯丝发出的 IR 辐射在最终到达旋转冷冻瓶之前穿过各种材料。通过将物理定律与蒙特卡罗模拟相结合来计算能量传递，并通过实验数据进行验证。评估了各种材料的传输特性对发射 IR 辐射谱的影响。这些结果有助于选择合适的材料，这些材料可以作为连续冷冻干燥原型中的 IR 窗。本文提出的建模框架适合于该原型开发中使用的基于模型的设计方法，并通过建立所需的工程参数和使工程师能够评估机械公差和材料选项，展示了这种设计策略的潜在优势。
