(302b) CFD-DEM Model for Fluidization Segregation during Transfer of Pharmaceutical Blends

This work presents a case study where detailed coupled computational-fluid-dynamics and discrete-element-method CFD-DEM models are used to identify and address powder segregation during a commercial-scale pharmaceutical tablet manufacturing operation. In this process, a well-blended powder mixture of active pharmaceutical ingredient (API) and several excipients is discharged from a bin blender through a long (~3 m) transfer chute before feeding into a tablet press. The tablets produced exhibited a systematic variation in content uniformity and evidence of segregation during the discharge process.

A coupled CFD-DEM modeling approach was selected to virtually simulate the process and probe the effects of material properties and process conditions in order to recognize the mechanisms responsible for segregation. The material properties were first calibrated using experimental measurements from the FT4 Powder Rheometer and the Schulze Ring Shear Tester. Next, the model (and input material parameters) were validated in a number of ways, including a comparison with a small-scale fluidization-segregation tester. Subsequently, simulations of the industrial-scale transfer chute were performed and the results successfully reproduced the segregation trends observed in the actual physical systemâ??air-driven segregation of dissimilar-sized API and excipient particles was identified to be the root cause of content uniformity variations.

This calibrated and validated CFD-DEM model offers an opportunity to virtually test various strategies to mitigate segregation. Specifically, alternative API particle size distributions were simulated with results indicating that an optimum API particle size distribution can help to reduce the risk of segregation. Thus, these CFD-DEM computational models have helped to improve the understanding of the source of segregation issues and guided the strategy to reduce the segregation risk during the manufacture of a commercial pharmaceutical product.