Multi-zonal compartmentalization methodology for surrogate modelling in continuous pharmaceutical manufacturing

Abstract Detailed process understanding of powder systems is important for ensuring regulation compliant manufacturing of pharmaceutical solid-based drug products. However, this can get challenging due to the current limitations in experimental and computational approaches, constraining the available knowledge of critical quality attributes. To address this drawback, we propose the use of computationally efficient and mechanistically informed surrogate models developed using multi-zonal compartmentalization methodology. In this work, the proposed modelling strategy is demonstrated for continuous powder blenders, wherein, first principle-based discrete element simulation is used to obtain an inter-connected network of zones for detailed evaluation of mixing within the system. The obtained surrogate models are further validated using the original simulation, illustrating the accuracy of the proposed methodology.