An impedance-based process analytical technology for monitoring the lyophilisation process

The aim of this work was to develop a minimally invasive, impedance spectroscopy method as a novel process analytical technology for monitoring the freeze drying process. This involved the application of planar electrodes, mounted externally to a conventional glass freeze-drying vial, coupled to a high-impedance analyser. The pseudo-relaxation process arising from the composite impedance of the glass wall and product interface was recorded over a frequency range 10(1)-10(6)Hz for a surrogate formulation comprising 2.5% sucrose. Features of the process (i.e. the peak amplitude, C"(peak) and characteristic peak frequency, fpeak) were monitored along with the product temperature data during the entire cycle. It was demonstrated that fpeak is strongly coupled to the temperature of the product (through the dependence of the product temperature on the electrical resistance of the product) whereas C"(peak) is dependent on the extent of ice sublimation and hence can be used to measure the rate of drying and end point of primary drying. This feature provides a distinct advantage over thermocouple measurements which are restricted to end point detection only. The potential to predict the end point of a cycle from C"(peak) vs. time profiles is highlighted in this work.