Influence of controlled nucleation by ultrasounds on ice morphology of frozen formulations for pharmaceutical proteins freeze-drying

In order to optimize industrial freeze-drying processes of pharmaceutical proteins in vials, an ultrasound system has been designed and applied to control the freezing step. It was confirmed that during supercooling, nucleation temperatures of the sample could be controlled at selected values below the equilibrium freezing temperature. Because the main freezing elementary phenomena like nucleation and ice crystals growth are strongly related with ice crystal morphology parameters, the controlled nucleation by ultrasound effectively modified notably the primary drying duration. Thus, it was experimentally confirmed that the primary drying rates during freeze-drying of pharmaceutical formulations (i.e. mannitol, BSA, sucrose) were accelerated due to ice phase morphological modifications induced by the ultrasound control system.