双氯芬酸钠肠溶片的逆向工程及处方优化  

Reverse engineering and formulation optimization of diclofenac sodium enteric-coated tablets

作　　者：温美强 杨俊 陈果 杨广雪 邹梅娟[1] 程刚[1] WEN Meiqiang;YANG Jun;CHEN Guo;YANG Guangxue;ZOU Meijuan;CHENG Gang(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2022年第11期1303-1311,1326,共10页Journal of Shenyang Pharmaceutical University

摘　　要：目的对双氯芬酸钠肠溶片进行逆向工程研究和处方优化,为该制剂的仿制提供参考。方法从定性研究、片芯辅料定量、药物晶型确证、包衣层结构及增重分析和制备工艺识别多个维度对参比制剂进行逆向研究,在此基础上进行自制制剂处方优化。制备3批样品,在4种介质中与参比制剂比较释放曲线。结果参比制剂拉曼光谱成像与文献调研结果一致。重量法和碘显色法可分别测定一水乳糖及玉米淀粉含量。酸中浸泡后剥离肠溶层及扫描电镜法可测定肠溶层增重及厚度。参比制剂为湿法制粒压片工艺且制备过程中药物晶型未发生变化。3批自制制剂与参比制剂在4种介质中释放曲线的相似因子f2均大于50。结论自制制剂与参比制剂在体外4种介质中释放行为相似。Objective To carry out reverse engineering research and prescription optimization of diclofenac sodium enteric-coated tablets, providing reference for the development of that generic drug.Methods The reference preparation was studied reversely from multiple dimensions, including qualitative study, excipients quantification, drug crystal confirmation, coating structure and weight gain analysis, and preparation process identification.On this basis, self-made preparation prescription optimization was performed.Three batches of samples were prepared and their release curves were compared with those of reference preparation in four different media.Results The Raman mapping of reference preparation was consistent with the result of literature investigation.Gravimetric method and iodine colorimetric method can be used to determine the content of lactose monohydrate and corn starch, respectively.The weight gain and thickness of enteric coating can be measured by stripping the enteric layer after soaking in acid and scanning electron microscopy respectively.The reference preparation was wet granulation process, and the crystal form of the drug did not change during the preparation process.The similarity factor f_(2) of the release curves of the three batches of self-made preparation and reference preparation was all greater than 50 in the four media.Conclusion The release behavior of self-made preparation is similar to that of reference preparation in four media in vitro.

关 键 词：双氯芬酸钠 肠溶片 参比制剂 逆向工程 处方优化 体外释放 

分 类 号：R94[医药卫生—药剂学]