药学学报, 2022, 57(4): 1147-1154
引用本文:
谢文影, 白玉菱, 赵孟涛, 周康明, 范仁宇, 管天冰, 任建兵, 孙会敏, 戴传云. 微晶纤维素的离散元仿真参数标定及休止角的细观分析[J]. 药学学报, 2022, 57(4): 1147-1154.
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. Calibration of discrete element simulation parameters and mesoscopic analysis of angle of repose of microcrystalline cellulose[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 1147-1154.

微晶纤维素的离散元仿真参数标定及休止角的细观分析
谢文影1, 白玉菱1, 赵孟涛1, 周康明1, 范仁宇1, 管天冰1, 任建兵1,2, 孙会敏3*, 戴传云1*
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
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。
关键词:    粉体      微晶纤维素      离散元      休止角      参数标定      细观角度     
Calibration of discrete element simulation parameters and mesoscopic analysis of angle of repose of microcrystalline cellulose
XIE Wen-ying1, BAI Yu-ling1, ZHAO Meng-tao1, ZHOU Kang-ming1, FAN Ren-yu1, GUAN Tian-bing1, REN Jian-bing1,2, SUN Hui-min3*, DAI Chuan-yun1*
1. Chongqing Key Laboratory of Industrial Fermentation Microorganisms, College of Chemistry and Chemical Engineering, Chongqing University of Science and Technology, Chongqing 401331, China;
2. Chongqing Liyun Nozzle Co., Ltd., Chongqing 401332, China;
3. 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
Abstract:
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.
Key words:    powder    microcrystalline cellulose    discrete element    angle of repose    parameters calibration    mesoscale angle   
收稿日期: 2021-07-09
DOI: 10.16438/j.0513-4870.2021-1011
基金项目: 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).
通讯作者: 孙会敏,Tel:86-10-53852486,E-mail:sunhm@126.com;戴传云,Tel:86-23-65022212,E-mail:cydai@126.com
Email: sunhm@126.com;cydai@126.com
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参考文献:
[1] Zhang Q, Xia XJ. Research progress on the interaction between drugs and excipients in pharmaceutical preparations[J]. Chin J Pharm (中国医药工业杂志), 2021, 52:32-41.
[2] Yu LF, Hu RF, Su D, et al. Characterization of microcrystalline cellulose fluidity and visualization of correlation of performance parameters[J]. Acta Pharm Sin (药学学报), 2018, 53:806-811.
[3] Zhang Y, Wei YF, Peng Z, et al. Research on inclined hourglass flow and the angle of repose of particles[J]. Acta Phys Sin (物理学报), 2016, 65:215-222.
[4] Roessler T, Katterfeld A. DEM parameter calibration of cohesive bulk materials using a simple angle of repose test[J]. Particuology, 2019, 45:105-115.
[5] Yeom SB, Ha ES, Kim MS, et al. Application of the discrete element method for manufacturing process simulation in the pharmaceutical industry[J]. Pharmaceutics, 2019, 11:414.
[6] Zhang Y, Xu B, Sun F, et al. Research and application of physical fingerprint of Chinese medicine extract powder[J]. China J Chin Mater Med (中国中药杂志), 2016, 41:2221-2227.
[7] Zheng XY, Zhang LK, Fu SB. Measurement of friction coefficient between propellant particles and its effect on packing density[J]. J Ball (弹道学报), 2019, 31:85-91.
[8] Cundall PA, Strack OD. A discrete numerical model for granular assemblies[J]. Geotechnique, 1979, 29:47-65.
[9] Itasca Consulting Group. PFC 5.0 Documentation[R]. Minneapolis:Itasca Consulting Group, 2014.
[10] Wensrich CM, Katterfeld A. Rolling friction as a technique for modeling particle shape in DEM[J]. Powder Technol, 2012, 217:409-417.
[11] Liu H, Ren FY, He RX, et al. Calibration method of PFC meso-parameters for simulating ore and rock[J]. Metal Mine (金属矿山), 2018, 1:37-41.
[12] Yong X, Xu C, Zhe Z, et al. 2D DEM simulation of particle mixing in rotating drum:a parametric study[J]. Particuology, 2010, 8:141-149.
[13] Jiang S, Duan C, Ye Y, et al. Discrete element simulation of factors affecting the fluidity of nylon powder[J]. Math Probl Eng, 2019, 2019:1-10.
[14] Amirsalar Y, Mohammadreza E, Farhad EM, et al. Mixing assessment of non-cohesive particles in a paddle mixer through experiments and discrete element method (DEM)[J]. Adv Powder Technol, 2018, 29:2693-2706.
[15] Chen QF, Wang SP, Qin SK. Discrete element simulation of the evolution characteristics of the rock force chain of the multi-funnel granular ore under the flexible isolation layer[J]. Chin J Eng (工程科学学报), 2020, 42:1119-1129.
[16] Zhou YC, Yu AB, Stewart RL, et al. Microdynamic analysis of the particle flow in a cylindrical bladed mixer[J]. Chem Eng Sci, 2004, 59:1343-1364.
[17] Shi CF, Yang MR, Tang ZX, et al. Study on the calibration method of discrete element simulation parameters of Chinese medicine infusion powder[J]. Chin Tradit Herb Drugs (中草药), 2020, 51:74-81.
[18] Mohajeri MJ, Helmons R, Rhee CV, et al. A hybrid particle-geometric scaling approach for elasto-plastic adhesive DEM contact models[J]. Powder Technol, 2020, 369:72-87.