Qualitative Assessment of a Multi-Scale, Compartmental PBM-DEM Model of a Continuous Twin-Screw Wet Granulation Process


Wet granulation processes play a crucial role in solid oral dosage manufacturing processes. However, they are often designed empirically with poor efficiency. To implement quality-by-design, a more scientific understanding is desired to predict the effects of process and equipment design and material properties on the rate mechanisms governing wet granulation processes. In this study, a multi-dimensional compartmental population balance model of a twin screw granulation process is coupled with discrete element method simulations to evaluate mechanistic rate expressions describing aggregation, breakage, consolidation, and particle flow. Steady-state results are presented for various configurations of the screw elements. The effects of screw element configuration on product size distribution, porosity, and liquid distribution are presented and compared with experimental trends described in literature. Simulated results are consistent with experimental findings, demonstrating the model’s qualitative ability to predict the effects of screw element design and configuration on the particle-scale phenomena and process outcomes.

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This work is supported by the National Science Foundation Engineering Research Center on Structured Organic Particulate Systems Grant NSF-ECC 0540855. The authors also thank Jim Litster (Purdue), Sean Bermingham (Process Systems Enterprise), Jianfeng Li (Process Systems Enterprise), Frances Pereira (Process Systems Enterprise), David Slade (Process Systems Enterprise), Ravindra Aglave (CD-adapco), Kristian Debus (CD-adapco), and Thomas Eppinger (CD-adapco) for contributing to discussions on this work.

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Correspondence to Rohit Ramachandran.

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Barrasso, D., Ramachandran, R. Qualitative Assessment of a Multi-Scale, Compartmental PBM-DEM Model of a Continuous Twin-Screw Wet Granulation Process. J Pharm Innov 11, 231–249 (2016). https://doi.org/10.1007/s12247-015-9240-7

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  • Twin screw granulation
  • Quality-by-Design
  • Population balance modeling
  • Discrete element method
  • Multi-scale modeling