MODELLING OF FREEZING STEP DURING VIALFREEZE-DRYING OF PHARMACEUTICALS.INFLUENCE OF NUCLEATION TEMPERATURE

摘要

A mathematical model that simulates temperature profiles during freezing process ofstandard pharmaceutical formulations was set up, and the ice crystal mean sizes weresemi empirically estimated from the resulting temperature profiles. Water vapour masstransfer permeability values during sublimation step were also estimated from ice phasemorphological parameters. All these numerical data were compared with experimentaldata, and a quite good agreement was observed which confirmed the adequacy of thepresent model calculations. It was confirmed that, for a given formulation, the masstransfer parameters during freeze-drying were strongly dependent on morphologicaltextural parameters, and consequently, on the nucleation temperatures that fix the icephase morphology. The influence of freezing rate was also predicted from thesimulations, proving that an increase of cooling rates led to slower primary drying rates.