Non-invasive temperature monitoring: controlled nucleation as a case study

Abstract

Freeze-drying is employed in pharmaceutical industry to preserve thermo-sensitive products. It is a cost intensive process and, for its optimisation, it is important to maximise the ice sublimation rate during primary drying, thus reducing cycle duration. At this purpose, it is fundamental to monitor the product temperature and keep it at a value lower than that at which melting or collapse occurs. The temperature monitoring is also important during the freezing stage as it influences the two subsequent drying stages. In particular, the temperature of ice nucleation determines the size of ice crystals and the morphology of the frozen cake, thus impacting on the final properties of the product. Moreover, as the nucleation of ice is a stochastic event and it is not certain that all the vials in the batch nucleate at the same temperature (allowing a non-homogeneous product structure and subsequent drying behaviour), several techniques have been proposed for inducing the nucleation at a certain temperature and time and make the process more cost efficient