Non-contact monitoring of the freeze-drying process of microparticles using microwave resonance spectroscopy

Spray freeze-drying has emerged as a promising alternative to conventional vial freeze-drying. In this study, we have developed a non-contact monitoring technique for the freeze-drying of microparticles utilizing microwave resonance spectroscopy. Spectral changes, indicative of the degree of drying, were successfully captured during the freeze-drying process of particulate samples ranging in size from approximately 0.6-3.5 mm. The observed spectral patterns demonstrated significant dependence on both the mean particle size and the formulation type (mannitol or sucrose). The partial least squares method was employed to extract data series strongly correlated with the drying progress. Multiple regression analysis was then utilized to derive regression equations, yielding values representing the drying progress based on the intensity values at selected frequencies within the spectra. The resulting regression equations accurately replicated the experimentally estimated drying kinetics. Notably, a robust regression equation was obtained, demonstrating applicability to various formulations and particle sizes, with coefficient of determination values ranging from 0.95 to 0.99. Furthermore, it was suggested that a correlation between the obtained spectra and the change in moisture content during secondary drying. Microwave resonance spectroscopy proves to be a versatile technique for monitoring freeze-drying processes, offering insights that can enhance the efficiency and adaptability of this critical pharmaceutical manufacturing step.