Optimizing the secondary drying phase of a continuous Spin-Freeze Drying process: A semi-mechanistic modelling approach

Over the past decade, continuous spin freeze-drying technology has emerged as a promising alternative to conventional batch freeze-drying, effectively addressing many of the latter’s inherent disadvantages. Much of the focus during this period has been on controlling and optimizing the primary drying phase of this process. However, optimizing the secondary drying step is equally critical for the overall efficiency of the process. The primary aim of this study was to develop a comprehensive semi-mechanistic model for the secondary drying phase in continuous spin freeze-drying, accounting for the effects of process settings such as freezing rate and product temperature on desorption kinetics. Additionally, the study aimed to address discrepancies between conventional desorption models, typically applied in batch freeze-drying, and the observed data in this research. To achieve this, a residual moisture-dependent activation energy was introduced to improve the accuracy of the desorption model. Using NIR spectroscopy and IR-thermography, unknown model parameters could reliably be estimated using a simple and fast procedure. The calibrated model successfully predicted the final moisture content with an accuracy within 0.11% of the measured value under previously untested process conditions. Ultimately, the proposed semi-mechanistic model demonstrated its reliability in predicting the impact of new process conditions on both product temperature and residual moisture over time, enabling the development of a practical design space. [Display omitted]