Observations on the Changing Shape of the Ice Mass and the Determination of the Sublimation End Point in Freeze-Drying: An Application for Through-Vial Impedance Spectroscopy (TVIS).

Models for ice sublimation from a freeze-drying vial rely on the assumption of a planar ice interface up to ~25% loss of ice mass (which is difficult to qualify) whereas single-vial determinations of the sublimation endpoint (by temperature sensors) are based on the point when the observed temperature reaches a plateau, which cannot differentiate between sublimation and desorption-drying. In this work, the real part capacitance of TVIS vial(s) containing frozen water (during sublimation drying) was measured at 100 kHz. This parameter C'(100 kHz) was shown to be highly sensitive to the shape and volume of the ice mass and is therefore a useful parameter for monitoring ice sublimation.