Spray freeze-drying of pharmaceuticals

Spray freeze-drying of pharmaceuticals In the pharmaceutical industry, freeze-drying technology is often used in medicines production since it ensures a more stable product both during shipping and storage. The lyophilized product strongly depends on how the freezing process is carried out. The final morphology, physicochemical properties and efficacy of its active principle all depend on this critical step. Therefore attention has to be given in the design of proper freezing and how it affects the dried product features by predicting the average size of solvent crystals formed. More specifically, we focus on Spray Freeze Drying, the most advanced and common way to perform lyophilization on both food and pharmaceutical products. This work focuses on developing a mechanistic model able to express the crystal size as a function of two parameters related to freezing. Hence physical theoretical background is given on the relationship between solvent crystal size, the velocity of the freezing front, and temperature gradients within the product being frozen. The model has been derived from an hentalphy balance made on the particle while the values of freezing front velocity and temperature gradients have been estimated by solving the governing equations on a simulating software and multiphysics solver COMSOL Multiphysics (vers. 5.3). This modellistic approach has been carried out at Politecnico of Turin. Model simulations were then validated upon experimental observations conducted at Kyoto University obtained by scanning electron microscopy(SEM). The average size of solvent crystals was determined from that of pores formed after the lyophilization of the frozen solutions in the cross-section of the particles. The developed model was demonstrated to be valid over a wide range of freezing conditions, and for solutions containing both amorphous and crystalline solutes.