星点设计效应面法优化汉防己碱纳米乳滴眼液的处方  

Optimization of formulation of Tetrandrine microemulsion eye drops based on pseudo-ternary phase diagrams and central composite design-response surface methodology

作　　者：杨颖 梁珍 李双君 张俊杰 YANG Ying;LIANG Zhen;LI Shuang-jun;ZHANG Jun-jie(Department of Ophtalmology People’s Hospital of Zhengzhou University,Zhengzhou 450003,China;不详)

机构地区：[1]郑州大学人民医院眼科 [2]河南省立眼科医院 [3]河南省眼科研究所,郑州450003

出　　处：《医药论坛杂志》2021年第6期1-5,9,共6页Journal of Medical Forum

基　　金：国家自然科学基金联合重点项目(U1704283);河南省科技厅基础与前沿项目(142300410057)。

摘　　要：目的采用伪三元相图联合星点设计效应面法(CCD-RSM)获得汉防己碱纳米乳(Tet-ME)滴眼液的最优处方。方法首先筛选汉防己碱在不同辅料中的溶解度,并初步评价液态脂质的成乳能力,然后采用伪三元相图法获得形成微乳的区域,通过微乳法制备Tet-ME,分别以药物/脂质(X1)、脂质/表面活性剂(X2)为考察对象,以粒径(Y1)、包封率(Y2)为评价指标,根据CCD-RSM计算获得Tet-ME的最优处方,并对最优处方进行验证。结果油酸、蓖麻油酸对汉防己碱均有较好的溶解能力,油酸成乳能力较好,根据CCD-RSM获得的最优处方为:汉防己碱0.04 g、油酸0.144 g,氢化蓖麻油1.44 g,甘油0.28 g,药物/脂质为0.278,脂质/表面活性剂为0.10,加水定容至20 mL。以最优处方制备的汉防己碱纳米微乳外观澄清透明,有淡蓝色乳光,pH值:6.28。平均粒径为(8.94±0.10)nm(n=3),与预估值偏差2.3%;包封率为(97.50±0.6)%,与预估值偏差1.5%。结论采用伪三元相图联合CCD-RSM获得的Tet-ME稳定且包封率高、粒径小,可用于后续研究。Objective To optimize the formulation of Tetrandrine microemulsion(Tet-ME) eye drops by combining pseudo-ternary phase diagrams and central composite design-response surface methodology(CCD-RSM).Methods Tetrandrine solubility in different excipients and the capacity of lipid emulsion were tested. The microemulsion region was obtained by the pseudo-ternary phase diagrams. Then the Tet-ME were prepared by microemulsion method. Drug/lipid(X1), lipid/surfactant(X2) were taken as individual factors, the particle size(Y1), encapsulation efficiency(Y2) were taken as the dependent factors. The possible optimum formulation was predicted by CCD-RSM and validated.Results Tetrandrine could be dissolved in oleic acid, ricinoleic acid. oleic acid had a good capacity of emulsion. The optimized formulation was Tetrandrine 0.04 g, oleic acid 0.144 g, hydrogenated castor oil 1.44 g, glycerin 0.28 g, drug-lipid ratio 0.278, and ratio of lipid to surfactant 0.10 and add water to 20 mL. According to the optimized formulation, the prepared tetrandrine microoemulsion were clear and transparent, with light blue opalescence.The pH was 6.28. The average particle size were(8.94±0.10)nm(n=3), the deviation was less than 2.3%, and the encapsulation efficiency were(97. 50±0.6) %, respectively. The deviation was less than 1.5%.Conclusion The stable and small size Tet-ME with high encapsulation efficiency could be obtained by combining pseudo-ternary phase diagrams and CCD-RSM.The prescription can be used for the preparation of terandrine microemulsion.

关 键 词：汉防己碱 纳米微乳 微乳法 伪三元相图 星点设计效应面法 

分 类 号：R944.1+5[医药卫生—药剂学]