阿戈美拉汀自微乳给药系统的制备和体外质量评价  

Preparation and quality evaluation of self-microemulsifying drug delivery systems for agomelatine

作　　者：黄燕飞 张强 张雪 程泽能 HUANG Yan-fei;ZHANG Qiang;ZHANG Xue;CHENG Ze-neng(School of Pharmacy,Xuzhou Medical University,Xuzhou Jiangsu 221000;Hunan Huize Bio-pharmaceutical Co.,Ltd.,Changsha 410000;Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410000)

机构地区：[1]徐州医科大学药学院,江苏徐州221000 [2]湖南慧泽生物医药科技有限公司,长沙410000 [3]中南大学湘雅药学院,长沙410000

出　　处：《中南药学》2022年第4期719-726,共8页Central South Pharmacy

摘　　要：目的使用星点设计-效应面法制备阿戈美拉汀自微乳并对其进行质量评价。方法通过考察阿戈美拉汀在不同辅料中的溶解度、油相与表面活性剂混合的相容性,绘制三元相图,确定处方所用辅料;运用星点设计-效应面优化法确定最终处方中辅料的比例。通过考察阿戈美拉汀自微乳的粒径稳定性(不同介质、不同稀释倍数、不同时间)、溶出试验,以及在不同影响因素[高温60℃、光照(4500±500)lx、避光25℃]下的含量变化,进行体外质量评价。结果阿戈美拉汀自微乳处方:油相Peceol 50 mg,Labrafil M1944CS 50 mg,表面活性剂RH40320 mg,助表面活性剂Transcutol HP 80 mg,阿戈美拉汀25 mg。分散得到粒径为(17.62±0.39)nm的微乳,以不同稀释倍数(1∶10、1∶50、1∶100、1∶200)和不同放置时间(0、3、6 h)在pH 1.0、pH 4.5、pH 6.8、水四种介质中考察,粒径均稳定,5 min溶出大于85%,且该制剂在高温、强光条件下含量未发生变化。结论本文研制出的阿戈美拉汀自微乳较稳定,有利于进一步开发。Objective To prepare agomelatine self-microemulsion by central composite design-response surface methodology and evaluate its quality.Methods The solubility of agomelatine in different excipients,compatibility of oil phase and emulsifier mixture were examined with ternary phase diagram to determine the excipients.The proportion of excipients in the final formulation was settled by central composite design-response surface methodology.The in vitro stability of droplet size(in different media,at different dilution ratios and different time),the dissolution test and the content changes under different influence factors[including 60℃,(4500±500)lx light,25℃dark]were determined to evaluate the quality of agomelatine self-microemulsion.Results The optimized formulation was composed of Peceol 50 mg,Labrafil M1944CS 50 mg,RH40320 mg,Transcutol HP 80 mg and agomelatine 25 mg.The microemulsions with particle size of(17.62±0.39)nm were obtained after dispersion.The microemulsions were constantly stable at pH 1.0,pH 4.5,pH 6.8 and water at different dilution ratios(1∶10,1∶50,1∶100 and 1∶200)and at different time(0,3,and 6 h).The dissolution was more than 85%at 5 min.The content of the preparation did not change under high temperature and strong light.Conclusion Stable agomelatine self-microemulsions are prepared,which is beneficial to further development.

关 键 词：阿戈美拉汀 自微乳给药系统 三元相图 星点设计-效应面法 溶出 

分 类 号：R944.1[医药卫生—药剂学]