基于偏最小二乘回归的红外光谱波段筛选用于甘露醇-氯化钙共晶的定量分析  

Infrared spectral band screening based on partial least squares is used for the quantitative analysis of mannitolcalcium chloride cocrystal

作　　者：李祖頔 张珂 张泽飞 钱帅[1] 魏元锋[1] 张建军[2] 高缘[1] LI Zu-di;ZHANG Ke;ZHANG Ze-fei;QIAN Shuai;WEI Yuan-feng;ZHANG Jian-jun;GAO Yuan(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China;School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院,江苏南京211198 [2]中国药科大学药学院,江苏南京211198

出　　处：《药学学报》2023年第4期1041-1048,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81873012,82074029,82104401);高校“双一流”项目(CPU2018GY11,CPU2018GY27);江苏省自然科学基金资助项目(SBK2020042291);中国博士后科学基金资助项目(2020M671665)。

摘　　要：甘露醇-氯化钙金属有机骨架(MOF)共晶显著改善了β-甘露醇的可压片性,可开发作为新型片剂填充剂,但研究者在该辅料放大生产过程中发现产物中含有甘露醇单体,显著影响辅料的功能特性。本研究拟对甘露醇-氯化钙共晶体系的多组分进行定量研究。实验以MOF共晶辅料甘露醇-氯化钙共晶为模型化合物,采集红外光谱,以偏最小二乘回归(PLSR)为基础,采用去除异常波段、归一化进行光谱预处理,采用遗传算法(GA)和竞争性自适应重加权算法(CARS)2种不同变量筛选方法筛选关键变量,建立并比较了共晶辅料制备产物中甘露醇-氯化钙MOF共晶含量的定量校正模型。采用GA法和CARS法2种不同变量筛选方法分别筛选出160、14个变量,CARS-PLSR法建立的甘露醇-氯化钙共晶模型具有最佳性能,模型的平均相对误差(MRE)和校正均方根误差(RMSEC)分别为0.0088和0.8925,与全光谱模型相比,模型的决定系数(R2)由0.9783提升为0.9944。本研究建立的共晶体系定量方法预测精度高、检测速度快、稳定性好,对优化此类共晶辅料制备工艺条件及质量控制方法的研究具有重要意义。Mannitol-calcium chloride metal organic framework(MOF)cocrystal significantly improved the tabletability ofβ-mannitol and could be developed as a new tablet filler.However,mannitol monomer was found in the product during the scale-up production of the excipient,which significantly affected the functional properties of the excipient.In this study,we intend to quantify the multi-component eutectic system of mannitol-calcium chloride.In this experiment,the MOF cocrystal excipient mannitol-calcium chloride cocrystal was used as the model compound,and infrared spectrum was collected.Based on partial least squares regression(PLSR)method,the abnormal bands were removed and the spectrum was preprocessed by normalization.The quantitative correction model of mannitol-calcium chloride MOF cocrystal content in cocrystal excipients was established and compared by two different variable screening methods,genetic algorithm(GA)and competitive adaptive reweighting algorithm(CARS).Two different variable screening methods,GA method and CARS method,were used to screen out 160 and 14 variables,respectively.The mannitol-calcium chloride cocrystal model established by CARS-PLSR method had the best performance,and the average relative error(MRE)and corrected root mean square error(RMSEC)of the model were 0.0088 and 0.8925,respectively,the determination coefficient(R2)of the model was increased from 0.9783 to 0.9944.The quantitative method of eutectic system established in this study has high prediction accuracy,fast detection speed and good stability,which is of great significance for optimizing the preparation process conditions and quality control methods of such eutectic excipients.

关 键 词：傅里叶红外光谱 偏最小二乘回归 甘露醇-氯化钙共晶 波段筛选 定量分析 

分 类 号：R917[医药卫生—药物分析学]