Rarefied porous flow in lyophilization: Review and open questions

This work presents the primary drying phase of pharmaceutical lyophilization (freeze drying) as a rarefied gas flow through a porous medium. The goal is to stimulate interest in this application among the rarefied gas flow community, as well as provide representative conditions and characterization of the typical porous structure. A literature review is presented on typical lyophilization process models, process conditions, and qualitative features of the porous structure. In particular, a key quantity for overall drying model accuracy is a mass transfer resistance Rp. Rp quantifies the resistance to a rarefied flow with 0.1 < Kn < 200 through a porous structure. This quantity is known to depend on drug composition, freezing protocol, and flow conditions, but no quantitative relationships exist. It is hoped that by linking these process conditions to porous microstructure and linking porous microstructure to macroscopic transport, Rp can be predicted.