The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development

Abstract

Through vial impedance spectroscopy (TVIS) is a product non-invasive process analytical technology which exploits the frequency dependence of the complex impedance spectrum of a composite object (i.e. the freeze-drying vial and its contents) in order to track the progression of the freeze-drying cycle. This work demonstrates the use of a dual electrode system, attached to the external surface of a type I glass tubing vial (nominal capacity 10 mL) in the prediction of (i) the ice interface temperatures at the sublimation front and at the base of the vial, and (ii) the primary drying rate. A value for the heat transfer coefficient (for a chamber pressure of 270 µbar) was then calculated from these parameters and shown to be comparable to that published by Tchessalov (2017).