Calibration of discrete element simulation parameters and mesoscopic analysis of angle of repose of microcrystalline cellulose

The development of the manufacturing process may require considerable time and resources from an economic perspective, which may result from the lack of cost-effective and reliable modeling tools of unit operation development in the pharmaceutical industry, in contrast to other chemical industries. Therefore, it is necessary to apply the modeling tools to the process, not only to overcome the challenges of regulatory and economic aspects but also to develop a more efficient and robust process. In response to this necessity, the modeling of the manufacturing process has been become increasingly important, as it can be applied to equipment design, improving process efficient, scale-up and unit operation development in the pharmaceutical industry. Discrete element method is a numerical method for predicting mechanical dynamics, such as position, velocity and motion of individual particles. First of all, the input parameters related to particle contact should be clearly defined. In this work, a calibration method of discrete element parameters was established and then elucidated the effects of different testing methods on repose angle of microcrystalline cellulose (MCC), from mesoscale angle. This experiment was composed of three parts:① Angle of repose measured by the lifting cylinder method (θ) was regarded as the response value of the model, and then discrete element simulation parameters were screened and optimized by Plackett-Burman, steepest climb and Box-Behnken test designs; ② The robustness of previous model was assessed by angle of repose measured by the funnel injection method (α) and the shear box method (φ) to obtain the best parameter combination generated from the model; ③ Based on accurate and reliable microscopic parameters, the formation mechanism of angle of repose was comprehensively investigated from the mesoscopic-angle perspective. The calibration results showed a robust and reliable parameter combination. Moreover, the lifting speed of lifting cylinder method and the height of funnel injection method all had a certain impact on the measurement results of angle of repose. Interesting, the evolution of force chains in the process of stacking with different angle of repose revealed a certain law in the perspective of mesoscopic-angle. Thus, the objective of present work is to provide a reference for discrete element simulation parameter calibration of other solid preparations and accurate simulation of materials in the pharmaceutical process such as mixing, transferring and tablet pressing.