Although spray drying is widely used to produce active pharmaceutical ingredients, its operation and improvement is often difficult to assess because of complex interactions between the chemical and physical properties of the solutions, and the ensuing fluid dynamic, and heat and mass transfer phenomena occurring during spray drying. Hence, computational fluid dynamics (CFD) modeling is used to provide insight into spray drying to produce pharmaceutical solid amorphous dispersions, the results of which are compared to experimental data from the modelled spray dryer during its operation. It is shown that droplets with different sizes, trajectories and breakup behaviors occur and cause droplet drying and solid powder formation differences that affect product characteristics. Based on the combined CFD and experimental information, a new drying approach is proposed and tested that is based on the precipitation of dissolved solid species and the introduction of swirl motion of the droplets during ejection from a spray nozzle. This new approach is shown to improve drying performance of difficult-to-handle pharmaceutical solutions. (C) 2018 Elsevier Ltd. All rights reserved.