Prediction of the Collapse of Freeze-Dried Lactose Solution using Through Vial Impedance Spectroscopy (TVIS)

The aim of this work is to evaluate the application of TVIS system for the prediction of micro-collapse during a freeze-drying cycle. The electrical impedance of a 5%w/v lactose solution contained within a modified glass freeze-drying vial was measured over the frequency range of 10 Hz to 1 MHz during the entire freeze-drying process. A significant decrease in CʺPEAK at the point of micro-collapse (as confirmed by SEM) highlights the potential for using TVIS for monitoring microscopic changes in the product resistance to vapour flow associated with the phenomenon of micro-collapse. This study also demonstrated a good correlation between TVIS data (Log FPEAK) and temperature of the frozen solution during the annealing stage of the cycle. By using a temperature calibration from the annealing stage it was possible to predict the onset of collapse and thereby demonstrate the potential for TVIS to be used as a process control tool that would allow the cycle to be driven at the highest achievable temperature whilst avoiding collapse.