The use of through vial impedance spectroscopy (TVIS) for determination of ice nucleation, solidification end point, and mannitol crystallization during freezing and re-heating. Poster presentation at the APS PharmSci Conference 11-13th September 2019 Greenwich, UK

This is a study of the freezing/reheating behavior of aqueous solutions of mannitol with respect to lyophilization process development given the prevalent use of the excipient. Here, through-vial impedance spectroscopy (TVIS) was used to study the thermophysical kinetics of an aqueous solution of 5%w/v mannitol during a freezing and re-heating phase of a freeze-drying cycle. Temperature calibration of the TVIS parameter F_PEAK enabled the determination of the ice nucleation temperature T_n at −13 ^oC while the ice solidification end point was observed based on the time profile of C' (0.2MHz), i.e. the real part capacitance at 0.2 MHz. A time difference of 20 min between the onset and end point then defines the ice solidification time t_i. A later step in C' (0.2MHz) indicated that mannitol crystallized at -32 ^oC and 20 minutes from end of ice solidification. Upon reheating at 0.2 ^oC/min, a large increase in C' (0.2MHz) was seen at −32 ^oC indicating the onset of melting of mannitol crystals which then lasted 20 min.