Industrial & Engineering Chemistry Research, Vol.47, No.21, 8445-8457, 2008
Dynamic Parameters Estimation Method: Advanced Manometric Temperature Measurement Approach for Freeze-Drying Monitoring of Pharmaceutical Solutions
The aim of this paper is to describe and validate the dynamic parameters estimation (DPE) method, a noninvasive in-line monitoring technique for the freeze-drying process of phrmaceuticals that only requires pressure measurement; simulations and experimental data of pharmaceutical solutions in vials are used to this purpose. This method has to be considered as an improvement of analogous techniques, such as the manometric temperature measurement (MTM) method, which are also based on the pressure rise analysis concept. The proposed approach is able to estimate not only the temperature profile inside the frozen product at any time during the pressure rise test, but also the position of the moving interface of sublimation, the external heat transfer coefficient, and the effective diffusivity coefficient in the dried product, which are necessary for a predictive model-based control algorithm. Fairly good estimations of the product temperature and of the transport parameters, as well as of the position of the interface of sublimation, which is directly related to the state of progression of the primary drying phase, are obtained along almost all the primary drying phase.