辅酶Q10眼用微乳的研制

Study on Coenzyme Q10 Microemulsion for Ocular Application

目的研制适合眼部用药的辅酶Q10微乳制剂。方法以溶解度、乳化效率及伪三元相图法筛选最佳油相、乳化剂及助乳化剂;以星点设计-效应面法及制备工艺的单因素考察,优化处方和工艺;并进行了辅酶Q10微乳制剂在角膜的滞留时间,辅酶Q10眼用微乳的稳定性初步评价以及家兔眼部刺激性实验的考察。结果经处方筛选和星点效应面法优化得出最佳处方为:MCT,Cremophor EL,Capmul MCM C8 EP分别为油相,乳化剂和助乳化剂,比例为3∶5∶2,药用浓度为10 mg·mL 1;乳化温度和时间对粒径没有明显影响;高温、强光考察10 d,粒径、pH值和含量均有明显变化,低温保存各指标没有变化明显;辅酶Q10微乳在家兔角膜滞留可达2 h;刺激性实验显示该制剂对家兔眼部无刺激性。结论该处方及工艺筛选、优化法简便可行,容易控制,制备的眼用微乳可延长在角膜的滞留时间,安全无刺激,低温避光保存稳定,适合眼部用药。

OBJECTIVE To prepare coenzyme Q10 microemulsion for topical ocular drug delivery. METHODS Select oil, surfactant and cosurfactant by solubility, emulsification efficiency and pseudo-ternary phase diagram method. Central composite design-response surface methodology and preparation of single factor was used to optimize formulation and process. Stability of coenzyrne Q 10 microemulsion, retention time of coenzyme Q 10 microemulsion in the cornea as well as the rabbit eye irritation were tested. RESULTS The obtained best formulation was MCT, Cremophor EL, Caprnul MCM C8 EP respectively as oil, surfactant and cosurfactant, the ratio was 3 ： 5 ： 2, coenzyme Q10 concentration was 10 mg-mL-1. The emulsification temperature and time bad no obvious influence. Stability experiment showed that particle size, pH value and content at low temperature had no obvious change, while at high temperature and strong light microemulsion was not stable. The coenzyme Q10 microemulsion could stay up 2 h in the rabbit cornea. Irritating experiments showed that the preparation bad no irritation to rabbit eye. CONCLUTION The optimization method of prescription and process is simple, feasible, and easy to control, the preparation can prolong residence time in the cornea, no irritation, and is stable saved under avoiding light and low temperature, suitable for eye drug use.