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

摘要： 对药品冻干过程进行优化的关键是在保证药品质量不受损害的情况下尽量缩短干燥时间。因此,对冻干过程进行准确的监控是十分重要的,既要保证药品的温度保持在合理的范围内,对干燥结束时间进行准确地判断,同时又要对冻干过程压力和温度进行良好的控制以达到冻干过程的最优化。本文对近年来药品真空冷冻干燥过程监控技术的研究进展进行了综述,主要有基于动态参数估计法(DPE)的监控系统、基于卡尔曼滤波法的监测系统、露点法判断一次干燥结束点、模型预测控制法(MPC)。提出药品真空冷冻干燥监控技术的研究应着重于以下几点:考虑辐射、对流和导热3种传热方式在冻干传热过程中所占的比重,建立二维、三维冻干模型以更加精确地监测药品冻干过程的参数,在此基础上研究对加热隔板温度和冻干室压力的实时最优控制策略,以对药品冻干过程进行及时、有效地控制。

关键词: 冷冻干燥, 一次干燥, 模拟, 监测, 控制