Mathematical modeling for the freeze-drying of micro- and nanoparticles in packed bed

The freeze-drying for particle-based materials is becoming of growing industrial relevance because ensures the production of dry powder drug products in the micron range, suitable for many pharmaceutical purposes. The use of particle-based material (commonly produced by spray-freezing[1]) has grown in recent years especially for the production of drugs designed for both oral and parenteral administration. Mathematical modelling can provide insights on the effect of structural parameters and operating conditions on the process behaviour, which can then be used to control the process ensuring the highest quality standards. As first step, mathematical modelling was used to investigate the effect of particle size distribution on the mass transport resistance of packed-bed made of frozen micro-particles. In particular, the structural properties of different packings (porosity and tortuosity) have been estimated by coupling bullet physics and Computational Fluid Dynamics. These results have then been used by a mechanistic model of the process in order to describe the product dynamics during primary drying and, thus, evaluate the impact of process conditions on process performances.