硝酸益康唑微乳凝胶的制备及其体外释放研究  

Preparation of Econazole Nitrate Microemulsion Gels and Its Release in Vitro Characteristics

作　　者：丁乐 杨人泽[2] 李小兰 肖人钟 欧阳文[2] 严金玲[2] 申音 魏桂林[2] DING Le;YANG Renze;LI Xiaolan;XIAO Renzhong;OUYANG Wen;YAN Jinling;SHEN Yin;WEI Guilin(Ganzhou Maternal and Child Health Care Hospital,Ganzhou,Jiangxi,China 341000;The First Affiliated Hospital of Gannan Medical University,Ganzhou,Jiangxi,China 341000;Jiangxi Angtai Pharmaceutical Co.,Ltd.,Jiujiang,Jiangxi,China 332300)

机构地区：[1]江西省赣州市妇幼保健院,江西赣州341000 [2]赣南医学院第一附属医院,江西赣州341000 [3]江西昂泰制药有限公司,江西九江332300

出　　处：《中国药业》2020年第13期35-38,共4页China Pharmaceuticals

基　　金：江西省自然科学基金[2015ZBAB205014];江西省科技计划项目[20152ACG70010]。

摘　　要：目的制备载药量高、黏附性好的硝酸益康唑微乳凝胶,以提高其透皮渗透和相对生物利用度。方法以表观溶解度评价硝酸益康唑在油、表面活性剂和助表面活性剂中的溶解度,筛选微乳的组分。以油酸乙酯为油相、Tween 80为表面活性剂、聚乙二醇400(PEG400)为助表面活性剂构建伪三元图。用卡波姆940制备微乳凝胶,加入硝酸益康唑微乳搅拌形成微乳凝胶。评估该系统的药物负载效率和表征pH、电导、黏度、粒度和药物含量。采用改良的Franz扩散池考察硝酸益康唑微乳凝胶的体外释放性能。结果表面活性剂与助表面活性剂之比为2∶1时,形成的微乳区域最大,微乳(F3)的球体尺寸为29. 88 nm;加入凝胶中微乳(F3)黏度从156. 73 mPa·s增至13. 6 Pa·s;体外扩散试验表明,微乳凝胶(FG3)的12 h累计渗透量为(51. 76±0. 35)%,显著高于硝酸益康唑普通凝胶的(36. 15±0. 42)%;Draize测试显示,硝酸益康唑微乳凝胶对大鼠皮肤无刺激,也无炎症迹象。结论硝酸益康唑微乳凝胶比其普通凝胶具有更好的应用性质和稳定性,有望成为硝酸益康唑的新型给药制剂。Objective To prepare econazole nitrate microemulsion gels with high drug content and adhesiveness to improve transdermal penetration and relative bioavailability of econazole nitrate.Methods The solubility of econazole nitrate in oils,surfactants and cosurfactants was evaluated by saturation solubility to screen the components of microemulsion.The pseudoternary phase diagrams were constructed using ethyl oleate as the oil phase,Tween 80 as surfactant and PEG 400 as the co-surfactant.Optimized formulation systems were formulated into gel form by using poloxamer-940.The system was assessed for drug-loading efficiency and characterized for pH,conductance,viscosity,particle size,drug content.Its release profile was characterized in vitro using a modified Franz diffusion cell.Results The microemulsion area formed was the largest when the ratio of surfactant to cosurfactant was 2∶1.The particle size of microemulsion(F3)was found to be 29.88 nm.The viscosity of microemulsion(F3)was found to be 156.73 mPa·s,but microemulsion gels was 13.6 Pa·s.In vitro diffusion study of drug showed increase in flux of microemulsion gels(51.76±0.35)%to that of simple econazole nitrate gel(36.15±0.42%).Draize test revealed absence of irritation and inflammation on rat skin.Conclusion Econazole nitrate microemulsion gels has better application properties and stability than its ordinary gel,and is expected to become a new drug delivery formulation of econazole nitrate.

关 键 词：微乳 凝胶 硝酸益康唑 经皮给药 渗透率 生物利用度 

分 类 号：R969.1[医药卫生—药理学] R978.5[医药卫生—药学]