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, Belgium OguguaLonginus SmithGeoffrey OrunAhmet 2019 <p>Studies of the freezing behavior of aqueous solutions of mannitol are highly relevant to lyophilization process development given the prevalent use of this excipient. Here, through-vial impedance spectroscopy (TVIS) was used to study the behaviour of an aqueous solution of 5%w/v mannitol during a freezing and re-heating cycle. Temperature calibration of the TVIS parameter F<sub>PEAK</sub> enabled the determination of the ice nucleation temperature T<sub>n</sub> at −13 <sup>o</sup>C 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<sub>i</sub>. A later step in C^' (0.2MHz) indicated that mannitol crystallized at -32 <sup>o</sup>C and 20 minutes from end of ice solidification. Upon reheating at 0.2 <sup>o</sup>C/min, a large increase in C' (0.2MHz) was seen at −32 <sup>o</sup>C indicating the onset of melting of mannitol crystals which then lasted 20 min.</p>