Process Understanding in Freeze-Drying Cycle Development: Applications for Through-Vial Impedance Spectroscopy (TVIS) in Mini-pilot Studies

Purpose The freeze-drying cycle comprises three stages: (1) freezing, to form ice and to crystallise out any solutes with a propensity to crystallise, (2) primary drying to remove the ice phase by sublimation and (3) secondary drying to remove the remaining unfrozen water which is bound to the remaining matrix of crystalline and amorphous solids. Given the impact of scale on the process outcomes, any freeze-drying cycle developed based on mini-pilot studies will inevitably require measurement technologies for characterising each stage of the cycle at each scale of the process. However, there are inherent challenges in the development of reliable mini-piloting studies, with the first being the fact that no single PAT technology for freeze drying may be implemented across all levels of scale, and the second being the inherent changes in process characteristics (process parameters that result from scale-up).