Development of a Nondestructive Monitoring Technique for Vial Freeze-Drying Process using Microwave Resonance Spectroscopy

Abstract

In this study, we developed a nondestructive monitoring technique for the drying progress of products in vials during the freeze-drying process using microwave resonance spectroscopy. An aqueous mannitol solution, commonly used as an excipient for injectable drugs, was used as the model material. The drying progress was determined using a mathematical model (i.e., Rp−Kv model), in which the parameters of mass and heat transfer were experimentally determined while considering the variation of the drying progress and position of the product on the drying shelf. A strong correlation was found between the extent of drying and changes in the microwave resonance spectrum. The simulation results were regressed against the changes in the resonance peak frequency and resonance intensity. Using this regression equation, the extent of drying could be predicted from the acquired spectral data. In this way, we were able to estimate the design space (the relationship between the operating conditions, internal temperature of the product, and sublimation rate), which changed with the extent of drying from the spectrum obtained inline, showing that it is possible to set the appropriate operating conditions based on the spectra.