(655a) Defining Suitable Process Operating Range for a Spray Dried Dispersion Using Combined Mechanistic and Statistical Modelling Tools

Spray drying dispersion (SDD) is a commonly used technology in drug manufacturing to improve solubility and dissolution behaviour of poorly soluble compounds. Designing a robust spray drying process and defining a feasible operating space at commercial scale are important in the highly regulated pharmaceutical industry. The use of computational tools can facilitate process development and design space analysis, while reducing experimental investigations and material consumption. In this work, we present a model-based workflow for spray drying processes, where a mechanistic model is utilized to identify key process parameters, such as gas/solution flowrates and processing temperatures, at large scale. Next, we evaluate a wide range of operating conditions and their impact on the physical stability of the SDD using data-driven correlations integrated within the mechanistic model, which allowed for the prediction of a broad operating space. Finally, a statistically designed experiment was used to determine the relationship between key process parameters and physical property attributes. The data from a reduced and well-defined set of experiments confirmed that desired quality attributes were achieved with a wide operating space.