A new method based on the regression of step response data for monitoring a freeze-drying cycle

This paper deals with the problem of monitoring the freeze-drying process of thermo-labile products and particularly tracking the temperature and the position of the interface of sublimation. A novel and affordable way is proposed to estimate the vapor flow rate and, thus, retrieve the parameters of interest. This method is referred to as pressure decrease test (PDT) and is based on the shutoff of the controlled leakage valve and on the subsequent model-based analysis of the response of the process. In this paper, a detailed description of the PDT algorithm is given; furthermore, the method was tested upon two placebo formulations, that is, sucrose- and mannitol-based solutions, showing that the tool can give an accurate, complete, and noninvasive estimation of all the parameters of interest. These results also show that the method is a valid solution to various technical problems that arise when attempting to apply other techniques proposed in the literature, for example, the pressure rise test and the tunable diode laser absorption spectroscopy technology.