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. By placing a digital camera in front of an isolated TVIS vial containing ice, it was possible to relate the changes in the shape of the ice mass with the changes in the trajectory of the time profile of C'(100 kHz) and determine the point of deviation from a planar ice interface and ultimately determine the point when the last vestiges of ice disappear. Thereafter, the same characteristics of the C'(100 kHz) time-profile were identified for those TVIS vials located out of sight of the camera in a separate full-shelf lyo study, thereby obviating the need for photographic examination.