Recent Developments in Pharmaceutical Spray Drying: Modeling, Process Optimization, and Emerging Trends with Machine Learning.

Spray drying techniques are widely used in the pharmaceutical industry to produce fine drug powders with different properties depending on the route of administration. Process parameters play a vital role in the critical quality attributes of the final product. This review highlights the progress and challenges in modeling the spray-drying process, with a focus on pharmaceutical applications. Computational fluid dynamics (CFD) is a well-known method used for the modeling and numerical simulation of spray drying processes. However, owing to their limitations, including high computational costs, experimental validation, and limited accuracy under complex spray drying conditions. Machine learning (ML) models have recently emerged as integral tools for modeling/optimizing the spray drying process. Despite promising accuracy, ML models depend on high-quality data and may fail to predict the influence of new formulation or process parameters on the properties of the dried powder. This review outlines the shortcomings of CFD modeling in the spray drying process. A hybrid model combining ML and CFD models, emerging techniques such as the digital twin approach, transfer learning, and explainable AI (XAI) are also discussed. A hybrid model combining ML and CFD models is also discussed. ML is considered an emerging technique that could assist the spray drying process, and most importantly, the utilization of this method in pharmaceutical spray drying.