口服固体制剂颗粒的离散元建模与破碎行为分析  

Discrete element modeling and breakage behavior analysis of oral solid dosage form particles

作　　者：罗林秀 管天冰 罗安琪 刘曾 王宇婷 姜彦伶 路政 唐劲草 陈双扣 孙会敏[2] 戴传云 LUO Lin-xiu;GUAN Tian-bing;LUO An-qi;LIU Zeng;WANG Yu-ting;JIANG Yan-ling;LU Zheng;TANG Jing-cao;CHEN Shuang-kou;SUN Hui-min;DAI Chuan-yun(School of and Chemical Engineering,Chongqing University of Science and Technology,Chongqing Key Laboratory of Pharmaceutical Digitalization,Chongqing 401331,China;National Institutes for Food and Drug Control,Beijing 100050,China)

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

出　　处：《药学学报》2024年第4期1057-1066,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);重庆市自然科学基金面上项目(CSTB2023NSCQ-MSX0712);重庆科技大学硕士研究生创新计划项目(YKJCX2220510).

摘　　要：单元颗粒在口服固体制剂(oral solid dosage forms,OSD)生产过程中的破碎规律与中间产品或终产品的质量息息相关。为精准表征颗粒和探索颗粒破碎演变规律,本论文采用离散元Bonding模型研究模型参数、颗粒形状和工艺条件(加载模式和加载速率)对颗粒破碎的影响,以动态形变、力-时间曲线、破碎率、最大碎片尺寸比和断裂强度等表征颗粒破碎规律。结果表明,颗粒破碎受力分别与法向强度、黏结半径呈正相关,与单位面积法向刚度、单位面积切向刚度呈负相关,与切向强度呈弱相关;颗粒的破碎率与颗粒的长径比呈负相关,最大碎片尺寸比与颗粒的长径比呈正相关;三种加载模式中,压缩加载破碎率最大,剪切加载破碎率次之,磨损加载破碎率最小,且最大碎片尺寸比与加载速率呈正相关,加载模式和加载速率对颗粒破碎率无相互影响,但对最大碎片尺寸比有相互影响。研究结果将为我国OSD由批制造向先进制造转变提供理论基础。The breakage pattern of unit particles during the production of oral solid dosage forms(OSD)is closely related to the quality of intermediate or final products.To accurately characterize the particles and study the evolution law of particle breakage,the Bonding model of the discrete element method(DEM)was used to investigate the breakage patterns of model parameters,particle shape and process conditions(loading mode and loading rate)on the dynamic breakage,force-time curve,breakage rate,maximum breakage size ratio and fracture strength of particles.The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale,negatively correlated with normal stiffness per unit area and tangential stiffness per unit area,and weakly correlated with tangential strength.The particle breakage rate was negatively correlated with the aspect ratio of the particles,and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles;among the three loading modes,the breakage rate of compression breakage model was the largest,the breakage rate of shear breakage model was the second largest,and the breakage rate of wear breakage model was the smallest;the maximum breakage size ratio was positively correlated with the loading rate,the loading mode and the loading rate had no mutual influence on particle breakage rate,but had mutual influence on the maximum breakage size ratio.The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

关 键 词：原辅料颗粒 离散元建模 Bonding模型 破碎规律 

分 类 号：R943[医药卫生—药剂学]