一线抗乙肝病毒药物恩替卡韦处方前研究  

Preformulation study on first-line anti-HBV drug entecavir

作　　者：蒋瑞 王腾腾 汤胜男 张艺雯 张鹏 张春燕[1] Jiang Rui;Wang Tengteng;Tang Shengnan;Zhang Yiwen;Zhang Peng;Zhang Chunyan(School of Pharmacy,Jining Medical University,Rizhao 276826,China;School of Pharmacy,Yantai University,Yantai 264005,China;The State Key Laboratory of Long-acting and Targeting Drug Delivery System,Luye Pharma Group,Yantai 264005,China)

机构地区：[1]济宁医学院药学院,日照276826 [2]烟台大学药学院,264005 [3]绿叶制药长效和靶向制剂国家重点实验室,烟台264005

出　　处：《国际医药卫生导报》2020年第15期2172-2178,共7页International Medicine and Health Guidance News

基　　金：济宁医学院大学生创新训练计划项目(cx2019024);山东省大学生创新创业训练计划项目(S201910443007)。

摘　　要：目的对耐药率低、抗病毒作用强的一线抗乙肝病毒药物恩替卡韦进行处方前研究,为开发其新型制剂提供参考和依据。方法对恩替卡韦外观、晶型和溶解性等进行考察,建立高效液相等度洗脱法进行含量测定,测定恩替卡韦在不同有机溶剂和不同磷酸盐缓冲液中的溶解性,以及其在不同pH条件下的表观油水分配系数。结果恩替卡韦为类白色结晶性粉末,无臭无味,易溶于二甲基亚砜,可溶于甲醇,难溶于乙腈、丙酮、二氯甲烷和乙酸乙酯。HPLC法在5~100μg·ml^-1浓度范围内线性关系良好(R=0.9999)。油水分配系数随pH值的升高而增大。结论本研究建立的定量测定恩替卡韦的HPLC法准确可靠,处方前研究表明,恩替卡韦微溶于水,难溶于多种有机溶剂,需采用适宜的方法进行恩替卡韦新制剂的开发。Objective To perform a preformulation study for entecavir,a first-line anti-HBV drug with low drug resistance and strong antiviral effect,so as to provide theoretical basis for the development of entecavir sustained-release microspheres.Methods The appearance,crystal form,and solubility of entecavir were investigated.A high performance liquid chromatography(HPLC)method for the quantitative determination of entecavir was established.The solubility of entecavir in different organic solvents and different phosphate buffers were determined,and the apparent oil-water partition coefficients at different pH conditions were measured.Results Entecavir was a white crystalline powder,odorless and tasteless.It is highly soluble in dimethyl sulfoxide,soluble in methanol,and difficult to soluble in some organic solvents such as acetonitrile,acetone,dichloromethane,and ethyl acetate.The quantitative HPLC method for the entecavir determination showed a good linearity in the range of 5-100μg/ml(R=0.9999).The oil-water partition coefficient increased with the increase of pH value.Conclusions The determination method of entecavir by HPLC established in this study is accurate and reliable.The present results indicate that entecavir is slightly soluble in water and insoluble in some organic solvents.The new entecavir preparations should be developed by suitable methods.

关 键 词：恩替卡韦 微球 处方前研究 溶解度 

分 类 号：R943[医药卫生—药剂学]