目的 采用休止角和流动能作为响应值进行仿真参数的联合标定，以提高离散元法模拟桂枝茯苓胶囊（Guizhi Fuling Capsules，GFC）制药过程的可靠性。方法 以GFC浸膏粉和辅料糊精为研究对象，通过休止角试验和旋转剪切试验分别测量2种粉末的休止角和流动能；基于颗粒缩放原理和Hertz-Mindlin with JKR V2接触模型，以休止角与流动能为响应值进行接触模型参数的联合标定；通过Plackett-Burman试验设计筛选出对休止角与流动能模拟测定影响显著的关键接触参数，应用最陡爬坡试验明确关键接触参数范围，通过Box-Behnken设计-响应面法建立关键接触参数与模拟休止角及流动能的回归模型和设计空间，结合满意度函数法在设计空间内确定最佳关键接触参数。结果GFC浸膏粉关键接触参数最佳组合为颗粒-颗粒碰撞恢复系数0.170、颗粒-颗粒滚动摩擦系数0.800、颗粒-钢静摩擦系数0.242、Johnson-Kendall-Roberts（JKR）表面能0.125 J/m²，糊精关键接触参数最佳组合为颗粒-颗粒碰撞恢复系数0.120、颗粒-颗滚动摩擦系数0.845、颗粒-钢静摩擦系数0.130、JKR表面能0.145 J/m²；采用上述优化结果进行离散元模拟，2种粉体休止角和流动能的模拟值与实测值相对误差均小于±1%。结论 与文献报道的采用单一方法进行GFC浸膏粉仿真参数标定的结果对比，证明了本方法标定的参数更加准确可靠，研究结果为GFC混合、制粒等制药过程的仿真实验奠定了基础。

Objective To improve the reliability of the discrete element method for simulating the pharmaceutical process of the Guizhi Fuling Capsules (GFC), the simulation parameters were co-calibrated using the angle of repose (AOR) and basic flow energy (BFE) as response values. Methods The GFC extract powders and excipient dextrin were taken as the research objects. The AOR and BFE of the two powders were measured by the AOR test and rotational shear test, respectively. Based on the particle scaling principle and the Hertz-Mindlin with JKR V2 contact model, the contact model parameters were co-calibrated in terms of AOR and BFE response values. The key contact parameters with significant effects on the AOR and BFE simulation were screened by using the Plackett-Burman experimental design. Then, the steepest climb test was applied to define the range of critical contact parameters. Finally, the regression model and design space of critical contact parameters with simulated AOR and BFE were established by the Box-Behnken design-response surface method, which is combined with the satisfaction function method to determine the optimal critical contact parameters in the design space. Results The optimal combination of key contact parameters of the GFC extract powders was as follows: particle-particle collision recovery coefficient 0.170, particle-particle rolling friction coefficient 0.800, particle-steel static friction coefficient 0.242, and Johnson-Kendall-Roberts (JKR) surface energy 0.125 J/m². The optimal combination of key contact parameters for dextrins was as follows: particle-particle collision recovery coefficient 0.120, particle-particle rolling friction coefficient 0.845, particle-steel static friction coefficient 0.130, and JKR surface energy 0.145 J/m². The preceding optimization results for discrete element simulation indicated that the relative error between the simulated and measured values of the AOR and BFE for both powders was less than ±1%. Conclusion In comparison with the results reported in the literature for the calibration of simulation parameters of the GFC extract powders using a single method, the results prove that the calibration parameters in this paper are more accurate and reliable. The results lay the foundation for the simulation experiments of pharmaceutical processes such as the mixing and granulation of GFC.

R283.6

国家工信部2023年产业基础再造和制造业高质量发展专项(TC2308068);中药制药过程控制与智能制造技术全国重点实验室开放基金课题(SKL2024Z0205);北京中医药大学基本科研业务(揭榜挂帅)项目(2023-JYB-JBZD-060)