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

Abstract

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.

Description

Keywords

Freeze drying, through vial impedance spectroscopy, collapse temperature

Citation

Jeeraruangrattana, Y., Polygalov, E., Ermolina, I., Smith, G. (2017) Prediction of the Collapse of Freeze-Dried Lactose Solution using Through Vial Impedance Spectroscopy (TVIS) [poster]. 8th APS International Pharm Sci, Hartfield, UK, September 2017.

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)