In-situ near-infrared spectroscopy monitoring of the lyophilization process

Purpose. The purpose of this work was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to monitor the freeze-drying process in-situ. Methods. The experiment was performed in a pilot-scale freeze-dryer, in which the NIRS probe was interfaced using a lead-through to the lyophilizer. Special equipment for the sample presentation was developed. NIRS measurements were made using a FT (Fourier transform)- NIR spectrometer fitted with a single fiber reflectance probe. Results. The physical changes, that is, freezing, sublimation, and desorption, generated significant spectral changes. There was good agreement between NIRS monitoring and product temperature monitoring about the freezing process and the transition from frozen solution to ice-free material. The NIRS monitoring also provided new information about the process that was not possible to detect with product temperature monitoring, such as the rate of the desorption process and the steady-state where the drying was complete. The NIRS monitoring yields significantly more information about the actual process and essentially explains the observed changes of the product temperature during the lyophilization process. Conclusions. NIRS monitoring is a viable tool for in-situ monitoring, both qualitatively and quantitatively. It can facilitate investigations of the drying process within a sample. The small volume monitored makes sample presentation very important.