(377b) A Multi-Scale Hybrid Modeling Approach for Continuous Pharmaceutical Unit Operations
AIChE Annual Meeting
Friday, November 20, 2020 - 8:15am to 8:30am
In this study, the proposed integration strategy is demonstrated for continuous blending unit operation using a sequential hybridization approach . Under the proposed approach, particle-scale information [5,6] from DEM simulations (using Simcenter STAR_CCM+ software) is obtained to develop a data-driven model. This data-driven model is then combined with a flowsheet model (developed in PSE gFORMULATE modeling platform ) to provide fast predictions for the entire production line. The combination of DEM simulation with flowsheet modeling via a data-driven approach is performed such that any process changes occurring in the process flowsheet are recorded and replicated in the DEM simulation. This allows DEM simulation to capture dynamic effects of process changes on particle mechanics, which is then transferred to update the data-driven model linked to the flowsheet. This approach allows the flowsheet to incorporate effects of real-time process dynamics on powder behavior. The proposed study focuses on the application of this approach for evaluation and prediction of cross-sectional blend uniformity within the blender. Given the difficulties encountered in experimental measurement of cross-sectional blend uniformity for continuous blenders [8,9], the proposed approach provides an alternative for accurate evaluation of blend uniformity with detailed insights into the effects of process design and operating parameters. Blend uniformity is a critical quality attribute for tablet manufacturing and its accurate evaluation can avoid non-conformity of the final product.
In conclusion, the proposed work focuses on incorporation of detailed particle-scale information obtained from high-fidelity simulations within flowsheet models using hybrid data-driven approaches. This increases the mechanistic understanding of powder systems while improving the predictive ability of flowsheet simulations. The integrated approach presented in this work for powder blending systems, can be extended for other unit operations for the construction of robust flowsheet models and allow the implementation of QbD for continuous pharmaceutical process development.
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