On the Design of an In-Line Control System for a Vial Freeze-Drying Process: The Role of Chamber Pressure

Abstract

This paper is focused on the design of an in-line control system for the freeze-drying process of pharmaceuticals in a vial. The goal is to minimize the duration of the primary drying, when most of the water is removed by sublimation while maintaining the product temperature below the maximum value allowed by the product. The pressure in the drying chamber and the temperature of the fluid that is used to heat (or to cool) the product can be manipulated; the pressure rise test and the DPE (Dynamic Parameters Estimation) algorithm are used to estimate the product temperature and the residual ice fraction, i.e. the controlled variables. Both an open-loop controller, using constant values of fluid temperature and chamber pressure, and a closed-loop controller, based on the in-line optimization of the fluid temperature, will be described and tested. Finally, the possibility of manipulating in-line the pressure in the drying chamber will be discussed.