微晶纤维素的离散元仿真参数标定及休止角的细观分析  

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

作　　者：谢文影 白玉菱 赵孟涛 周康明 范仁宇 管天冰 任建兵 孙会敏[3] 戴传云[1] XIE Wen-ying;BAI Yu-ling;ZHAO Meng-tao;ZHOU Kang-ming;FAN Ren-yu;GUAN Tian-bing;REN Jian-bing;SUN Hui-min;DAI Chuan-yun(Chongqing Key Laboratory of Industrial Fermentation Microorganisms,College of Chemistry and Chemical Engineering,Chongqing University of Science and Technology,Chongqing 401331,China;Chongqing Liyun Nozzle Co.,Ltd.,Chongqing 401332,China;Key Laboratory of Quality Research and Evaluation of Pharmaceutical Excipients of the State Drug Administration,National Institutes for Food and Drug Control,Beijing 100050,China)

机构地区：[1]重庆科技学院化学化工学院,工业发酵微生物重庆市重点实验室,重庆401331 [2]重庆力耘喷嘴有限公司,重庆401332 [3]中国食品药品检定研究院,国家药品监督管理局药用辅料质量研究与评价重点实验室,北京100050

出　　处：《药学学报》2022年第4期1147-1154,共8页Acta Pharmaceutica Sinica

基　　金：国家科技重大新药创制专项资助项目(2017ZX09101-001-006);重庆市技术创新与应用发展专项面上项目(cstc2020jscx-msxmX0048)。

摘　　要：本研究通过建立微晶纤维素(MCC)离散元参数标定方法,并以此探究不同测定方法对休止角存在影响的原因。以提升缸法休止角为响应值,通过Plackett-Burman、最陡爬坡及Box-Behnken等试验设计,筛选并优化离散元仿真参数,以漏斗注入法休止角和剪切盒法休止角进行稳健性考察,以期获得最佳参数组合,在此基础上,从细观角度分析休止角形成机制。结果表明,该方法标定的参数组合稳健可靠,提升缸法中提升速度和漏斗注入法中漏斗高度对休止角测量结果有一定影响,从细观角度分析了不同休止角堆积过程内部力链演变规律的差异。本研究可为固体制剂其他物料的离散元仿真参数标定及物料在下一步的混合、转移、压片等制药过程的准确模拟提供参考和思路。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 injectio

关 键 词：粉体 微晶纤维素 离散元 休止角 参数标定 细观角度 

分 类 号：R943[医药卫生—药剂学]