(55a) A Multi-Scale Modeling Approach to Continuous Blending Processes

Continuous processing is attracting increasing attention within the pharmaceutical industry today because it could lead to significant decreases in production costs while improving product quality. Regulatory authorities have also recognized the potential for improved QbD brought about by continuous processing. Within this, continuous blending is becoming an increasingly common process in industries that handle particulate material with the purpose of producing a homogenous blend with desired properties. Critical quality attributes such as API composition, relative standard deviation (RSD) of the composition and even particle size distribution (PSD) have to be tightly controlled due to the stringent quality control measures imposed.

This study focuses on the development of a hybrid population balance model and discrete element model (PBM-DEM) that addresses the multi-scale nature of the blending dynamics. The DEM model simulates the micro-scale particle-level behaviour and the resulting axial and radial fluxes are incorporated into the meso-scale particle cluster-level to simulate the key particle/blend properties. Results show the potential for the overall model to qualitatively predict trends in the literature (residence time distribution, RSD, API composition) and even particle size distribution changes (for a case of cohesive particles) at a fraction of the time taken for a full DEM simulation.