Experimental Study and Modeling of Freeze-Drying in Syringe Configuration. Part I: Freezing Step

This article concerns the experimental study and the modeling of the freezing step during freeze-drying of a model lyoprotectant formulation in syringe configuration. First, ice crystal morphology observations were carried out in a cold chamber equipped with stereomicroscopy to determine the ice crystal size distribution. We observed that the ice crystal morphology was homogeneous as a function of the radial position and that, contrary to our previous observations in glass vial configuration, no significant ice morphology differences existed between the bottom and the top of syringes. Thus, it seems that the gas cooling by free convection at the walls of the syringe during the freezing step led to higher homogeneity in the ice crystal morphology. These data allowed calculation of the mean ice crystal diameter (which was supposed to represent the mean porous diameter) and then the permeability of the freeze-dried cake. Moreover, a two-dimensional axisymmetric (2D) mathematical model in cylindrical geometry of the freezing step for aqueous sucrose solution was elaborated. It has been proved that this model was able to simulate quite precisely the whole temperature profiles during the freezing step, except the exothermic peak of nucleation. In the last part of this work on syringe geometry, the impact of annealing treatments on the freeze-dried matrix morphology was investigated. Some heterogeneity of sublimation rates was observed, with significant variation of residual humidity. Additionally, the water vapor mass transfer resistance values decreased if a convenient annealing treatment (shelf temperature at ?10°C) was applied.