Experimental study of the impact of annealing on ice structure and mass transfer parameters during freeze-drying of a pharmaceutical formulation.

The principal aim of this study is to evaluate the influence of annealing on structural properties and mass transfer parameters of a model formulation used for freeze-drying of pharmaceutical proteins. Characterization runs on ice morphology of the frozen material were performed in a cold chamber by direct optical microscopy using episcopic coaxial lighting. Consequently, it was possible to quantify the influence of annealing (temperature, duration) on ice morphology. Then, the pressure rise analysis method was used during primary drying to identify as a function of time both the dried layer mass transfer resistance values, R(p), and the sublimation front temperature, T(i), with or without annealing. Annealing turned out to accelerate sublimation rates by increasing ice crystal sizes of the frozen matrix, thus leading to lower values of R(p). Finally, secondary drying kinetics were studied by measuring the values of the desorption constant by a simple gravimetric method. In this study, annealing turned out to decrease desorption kinetics by a factor of two.