(423f) Development and Application of a MULTI-Component MODEL with Radially-Dependent Droplet Drying for Pharmaceutical Spray Drying

Spray drying is commonly employed in the pharmaceutical industry to form amorphous solid dispersions (ASD) that enhance the dissolution properties of the active pharmaceutical ingredient (API) in the drug product. Effective process design is essential to ensure desired product properties such as particle size and residual solvent content, while maintaining satisfactory physical stability. By combining the use of digital tools with experimentation, the design and scale up of spray drying processes may be improved.

In this work, we detail the development of a multi-component spray drying model in the gPROMS FormulatedProducts (gFP) framework with two distinct modules: 1) A heat and mass balance spray dryer process model, and 2) A droplet drying model with radial diffusion of components. More advanced thermodynamic models within gFP (e.g., NRTL) as well as dynamic vapor sorption (DVS) and differential scanning calorimetry (DSC) data can be used to inform the first module to simulate the predict product physical stability. With information of the liquid diffusion properties of solid components to inform the second module, the radial distribution of components across the particles may be predicted, allowing the model to predict shell locking. The model may be applied to predict a number of measurable product properties (e.g., particle size, solvent content, glass transition temperature) and their sensitivity to process parameters (e.g. drying gas temperature, solution feed rate, etc.), as well as be used to improve the environmental footprint of the process via reduced process mass intensity (PMI). The model may be utilized from early to late stages of pharmaceutical development, based on the level of knowledge of system properties, to improve and accelerate the development of pharmaceutical spray dried amorphous dispersions. Last, we demonstrate the use of this model for a case study of a pharmaceutical spray dried amorphous dispersion to predict the impact of process conditions on residual solvent content, glass transition temperature with a comparison to experimental process data and identify ranges of process parameters which yield desirable product qualities.