Temperature/end point monitoring and modelling of a batch freeze-drying process using an infrared camera

Temperature monitoring and accurate drying end time determination are crucial for final product quality in vacuum freeze-drying of pharmaceuticals. Whether crystalline or amorphous solutes are used in the formulation, product temperature during ice sublimation should be kept below a threshold limit to avoid damage to the product structure. Hence, there is a need to continuously monitor product temperature throughout the process. Current monitoring tools, such as thermocouples and Pirani gauge pressure sensors, have several limitations such as affecting product dynamics or imprecise end point determination. In this work, a monitoring tool based on infrared (IR) thermography is used for batch freeze-drying processes. Batches using three different vial sizes, with up to 157 vials, were studied, allowing to extend and better describe the representativeness of IR thermography for this application. The detailed axial temperature profiles obtained through IR imaging allowed not only a comprehensive non-invasive temperature monitoring of the product, but also tracking of the sublimation interface. IR temperature measurements and primary drying end point determination were compared to standard methods and thus verified. Parameters important for freeze drying design space calculation, namely the global heat coefficient (K_v) and cake resistance to vapor flow (R_p), were also accurately estimated with the proposed method.