难溶性药物盐酸奈必洛尔口服自微乳化给药系统的制备以及体外评价

Preparation and in Vitro Evaluation of a Self-Microemulsifying Drug Delivery System for Insoluble Drug Nebivolol Hydrochloride

关键词:  盐酸奈必洛尔  自微乳化给药系统  伪三元相图法  星点设计-效应面法  溶出速率

Key words:  nebivolol hydrochloride  self-microemulsifying drug delivery system  pseudo-ternary phase diagrams  central composite design-response surface method  dissolution rate

摘要:

目的 制备盐酸奈必洛尔(hydrochloride，NBH)自微乳化给药系统(self-microemulsifying drug delivery system，SMEDDS)，并进行体外评价。方法 通过测定NBH在不同油相、表面活性剂和助表面活性剂中的溶解度以及运用伪三元相图对空白自微乳化的处方组成进行确定，使用星点设计-效应面法对处方用量进行筛选和优化，并加入过量NBH原料药对该处方的载药量进行确定。结果 NBH-SMEDDS处方组成为中链甘油三酸酯∶辛酸癸酸聚乙二醇甘油酯∶二乙二醇单乙基醚=20∶48∶32，该处方的载药量为20.05 mg，该处方的粒径、自乳化时间、粒径分布范围符合预测值，溶出度试验显示，NBH-SMEDDS在介质中溶出度的整体趋势对比NBH粉末和NBH普通片有一定的提升，在1，2，3月的加速条件下稳定性良好。结论 SMEDDS可用于提高NBH的体外溶出度，且稳定性良好。

Abstract:

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity.RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.