Archive | 2019
Application of through vial impedance spectroscopy (TVIS) for the determination of ice nucleation, solidification endpoint, and mannitol crystallization and melt-back temperature during freezing and annealing.Poster presentation at ISL-FD 9th International Conference 2-6th September, 2019, Ghent, Be
Abstract
Studies of the\nfreezing behavior of aqueous solutions of mannitol are highly relevant to\nlyophilization process development given the prevalent use of this excipient.\nHere, through-vial impedance spectroscopy (TVIS) was used to study the\nbehaviour of an aqueous solution of 5%w/v mannitol during a freezing and\nre-heating cycle. Temperature calibration of the TVIS parameter FPEAK\nenabled the determination of the ice nucleation temperature Tn at\nā13 oC while the ice solidification end point was observed based on\nthe time profile of C (0.2MHz), i.e. the real part capacitance at 0.2 MHz. A\ntime difference of 20 min between the onset and end point then defines the ice\nsolidification time ti. A later step in C^ (0.2MHz) indicated that\nmannitol crystallized at -32 oC and 20 minutes from end of ice\nsolidification. Upon reheating at 0.2 oC/min, a large increase in C \n(0.2MHz) was seen at ā32 oC indicating the onset of melting of\nmannitol crystals which then lasted 20 min.