Modeling of freezing step during. freeze-drying of drugs in vials

A mathematical model that simulates temperature profiles during freezing process of standard pharmaceutical formulations (mannitol and BSA based) was set up in two-dimensional axsymmetric space, and the ice crystal mean sizes were semi empirically estimated from the resulting temperature profiles. Water vapor mass transfer permeability values during sublimation step were also estimated from ice phase morphological parameters. All these numerical data were compared with experimental data, and a quite good agreement was observed that confirmed the adequacy of the present model calculations. It was confirmed that, for a given formulation, the mass transfer parameters during freeze-drying were strongly dependent on morphological textural parameters, and consequently, on the nucleation temperatures that fix the ice phase morphology. The influence of freezing rate was also predicted from the simulations, proving that an increase of cooling rates led to slower primary drying rates. (c) 2007 American Institute of Chemical Engineers.