关键词: 冷冻干燥, 一次干燥, 模拟, 监测, 控制

Abstract: For the optimization of pharmaceutical freeze-drying process, the key is to shorten the drying time as much as possible and keep the good quality of the product. Therefore, it is very important to monitor and control the freeze-drying process precisely, i.e., to keep the temperature of product within a reasonable range, judge the end point of drying time accurately, and a good control of chamber pressure and shelf temperature is needed to optimize the process. Research progress in pharmaceutical freeze-drying process monitoring and control technology in recent years is summarized in this paper, including monitoring system based on dynamic parameters estimation (DPE), monitoring system based on Kalman filter method, dew point method to judge the end point of primary drying, and model predictive control (MPC). The following points should be taken into account for further research on pharmaceutical freeze-drying monitoring and control technology. The contribution of three different heat transfer modes (radiation, convection, and conduction) should be investigated, so that a two-dimensional or three-dimensional model of pharmaceutical lyophilization in vials can be built, and more precise monitoring of process parameters can be obtained; Real-time optimal control strategy of shelf temperature and chamber pressure should be studied, with the aim of controlling pharmaceutical freeze-drying process timely and effectively.

Key words: freeze-drying, primary drying, modeling, monitoring, control