Amorphous solid dispersions (ASDs) are a widely utilized formulation technique to enhance the solubility and oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). Spray drying is the most used process for manufacturing these ASD-based drug products, especially when handling thermolabile drug substances. Despite its significance in the pharmaceutical industry, developing successful spray drying processes for ASDs is complex and often require experiments that consume considerable time and resources. Predictive modeling approaches are essential for the rapid and low-risk development of effective spray drying processes. This need drives the present work, in which we apply multiphysics simulation techniques to predict the process design spaces of spray drying processes for ASDs in industrial-scale pharmaceutical spray dryers. The proposed multiphysics simulation approach consists of a Lagrangian particle tracking (LPT) within a wall-modeled large eddy simulation (LES) framework. The drying process is modeled using a multi-component evaporation model that includes a characteristic drying curve approach, crust formation modeling, and droplet shrinkage. For comparison purposes, experiments were conducted on an industrial-scale spray dryer, specifically the GEA PHARMA-SD Type PSD-1, using pure solvent and excipient/solvent solutions. The results demonstrate that the proposed holistic numerical approach allows for accurate predictions of the complete process design space including all the relevant spray drying process conditions, such as outlet temperature, residence time distribution, residual solvent content and particle size distribution. Finally, the effects of thermal degradation and particle adhesion risk within the GEA PHARMA-SD Type PSD-1 spray dryer are also discussed.
