A diffused-interface model for the lyophilization of a packed bed of spray-frozen particles

Spray freeze-drying is particularly suitable for the preservation of biopharmaceuticals as it involves gentle drying and can easily be integrated with continuous manufacturing strategies. This process is still an evolving application, and its potential is often being explored experimentally. However, experimental methods are expensive and time-consuming. Therefore, much effort is currently focused on the development of mathematical models to understand the basic mechanisms and hence lay the foundation for analysis and experimentation. Even though a few models were proposed in the past, all of them presented various flaws and failed in describing the process behavior. We propose a multiscale approach, which is able to reproduce the structure of a packing of spray-frozen particles and extract detailed pore-scale geometrical features, informing the final vial-scale drying and heat transfer simulation. This latter step is the main innovation here presented, a new model that is based on the concept of a diffused interface and describes the process in a more accurate way.