二元混合颗粒压制过程离散元物性参数标定方法研究  

Research on the calibration method of discrete element physical property parameters in the pressing process of binary mixed particles

作　　者：罗安琪 赵孟涛 马驰 肖琴 路政 管天冰 陈双扣 孙会敏[2] 黄海军 王爱平 戴传云 LUO An-qi;ZHAO Meng-tao;MA Chi;XIAO Qin;LU Zheng;GUAN Tian-bing;CHEN Shuang-kou;SUN Hui-min;HUANG Hai-jun;WANG Ai-ping;DAI Chuan-yun(College of Chemistry and Chemical Engineering,Chongqing University of Science and Technology,Chongqing 401331,China;China National Institute for Food and Drug Control,Beijing 100050,China;Chongqing Key Laboratory of Digitalization of Pharmaceutical Processes,College of Traditional Chinese Medicine,Chongqing University of Chinese Medicine,Chongqing 402760,China)

机构地区：[1]重庆科技大学化学化工学院,重庆401331 [2]中国食品药品检定研究院,北京100050 [3]重庆中医药学院中药学院,制药过程数字化重庆市重点实验室,重庆402760

出　　处：《药学学报》2025年第4期1137-1146,共10页Acta Pharmaceutica Sinica

基　　金：重庆市自然科学基金创新发展联合基金项目(2023NSCQ-LZX0187);重庆市自然基金面上项目(CSTB2023NSCQ-MSX0712)。

摘　　要：针对现阶段研究片剂压制过程中微观力学行为常局限于唯象研究的问题,准确标定二元颗粒的离散元模型参数,是开展片剂压制建模研究的先决条件。本研究以预胶化淀粉和微晶纤维素为研究对象,应用Edinburgh elasto-plastic adhesion(EEPA)接触模型建立二元物料压制离散元仿真模型。以片剂压力-硬度、压力-体积减少量为响应值,应用Plackett-Burman设计、拉丁超立方抽样、Kriging模型,以及非支配排序遗传算法(NSGA-Ⅱ)标定得到显著影响片剂压制的离散元(discrete element method,DEM)参数最优值。结果表明,预胶化淀粉的DEM参数的最佳组合,即泊松比0.257、剪切模量1×10~9 Pa、颗粒-颗粒间静摩擦系数0.165、单位法向刚度2.4192×10~9N·m^(3)、单位切向刚度7.9546×10~9N·m^(-3)、黏附力强度-0.0091558 N;微晶纤维素的DEM参数的最佳组合,即泊松比0.381、剪切模量1.04×10~9 Pa、颗粒-颗粒间静摩擦系数0.719、单位法向刚度3.1715×10~9N·m^(-3)、单位切向刚度6.7462×10~9N·m^(-3)、黏附力强度-0.0387 N;二元混合辅料间的DEM参数的最佳组合,即颗粒-颗粒间碰撞恢复系数0.1,单位法向刚度9.9471×10~9N·m^(-3),单位切向刚度1.9945×10~9N·m^(-3),黏附力强度-0.06035 N。最佳参数组合下的模拟与物理实验结果相似,表明标定得到的参数可用于离散元仿真研究,为后续片剂的智能化与连续化生产提供理论基础和数据支撑。The study of micromechanical behavior during tablet pressing is often limited to phenomenological studies,accurate calibration of the discrete element model parameters of binary particles is a prerequisite for conducting modeling research on tablet compression.In this study,we take pregelatinized starch and microcry stalline cellulose as the research objects,and apply the Edinburgh elasto-plastic adhesion(EEPA)contact model to establish a discrete elemental simulation model for binary material pressing.Taking tablet force-hardness and force-volume reduction as response values,the optimal values of the discrete meta-parameters that significantly affect tablet pressing are obtained by applying Plackett-Burman design,Latin hypercubic sampling,Kriging model,and Non-dominated Sorting Genetic Algorithm(NSGA-Ⅱ)calibration.The results obtained the optimum combination of discrete element method(DEM)parameters for pregelatinized starch,Poisson's ratio 0.257,shear modulus1×10~9 Pa,granule-particle static friction coefficient 0.165,unit normal stiffness 2.4192×10~9 N·m^(-3),unit tangential stiffness 7.9546×10~9 N·m^(-3),and strength of adhesive force-0.0091558 N.For microcrystalline cellulose,Poisson's ratio 0.381,shear modulus 1.04×10~9 Pa,particle-particle static friction coefficient 0.719,unit normal stiffness3.1715×10~9 N·m^(-3),unit tangential stiffness 6.7462×10~9 N·m^(-3),and strength of adhesion-0.0387 N.For optimum combinations of the DEM parameters for the binary blend of excipients,particle-particle collision recovery coefficient0.1,unit normal stiffness 9.9471×10~9 N·m^(-3),unit tangential stiffness 1.9945×10~9 N·m^(-3),and adhesion force strength-0.06035.The simulation results under the optimal parameter combination are similar to the experimental results,indicating that the calibrated parameters can be used for discrete element simulation research and provide theoretical basis and data support for the subsequent intelligent and continuous production of tablets.

关 键 词：二元混合颗粒 离散元法 参数标定 压缩 

分 类 号：R943[医药卫生—药剂学]