正交设计优化盐酸川芎嗪脂质体的制备工艺

Optimization of Preparation Technology of Ligustrazine Hydrochloride Liposomes by Orthogonal Design

摘要:

目的: 优选盐酸川芎嗪脂质体的制备工艺,为川芎嗪的临床应用提供参考.方法: 采用HPLC测定盐酸川芎嗪含量,流动相甲醇-0.2%三乙胺水溶液(加冰乙酸调节pH 5.0)(60:40),检测波长295 nm.利用薄膜分散法制备盐酸川芎嗪脂质体,以包封率为评价指标,磷脂和胆固醇为膜材,通过正交试验考察水合时间、胆固醇和磷脂质量比、盐酸川芎嗪和磷脂质量比、磷脂质量分数对制备工艺的影响,考察脂质体包封率、形态、粒径、稳定性和Zeta电位.结果: 最佳制备工艺条件为水合时间30 min,胆固醇-磷脂(1:2),盐酸川芎嗪-磷脂(1:15),磷脂质量分数3%;盐酸川芎嗪脂质体包封率(70.27±0.58)%,外观接近球形,粒径(22.9±6.8)nm,Zeta 电位(-29.79±1.24)mV,于4 ℃保存2周后稳定性良好.结论: 优选的制备工艺合理、稳定,可促进盐酸川芎嗪的体内吸收并延长其作用时间.

Abstract:

Objective:To optimize preparation technology of ligustrazine hydrochloride liposomes which provides a reference for clinical application of ligustrazine. Method: Ligustrazine hydrochloride was quantified by HPLC method, mobile phase consisted of methanol-0.2% triethylamine solution(glacial acetic acid adjusted pH to 5.0)(60: 40) with detection wavelength of 295 nm.Ligustrazine hydrochloride liposomes were prepared by film dispersion method with phospholipid and cholesterol as raw materials, taking encapsulation efficiency as index, orthogonal design was adopted to optimize preparation process with hydration time, weight ratio of cholesterol to phospholipid, weight ratio of ligustrazine hydrochloride to phospholipid and the concentration of phospholipid as factors.encapsulation efficiency, morphology, particle size, Zeta potential and stability of ligustrazine hydrochloride liposomes were investigated. Result: Optimum preparation technology was as follows:hydration time of 30 min, ratio of cholesterol to phospholipid 1: 2, ratio of ligustrazine hydrochloride to phospholipid 1: 15, the concentration of phospholipid 3%;under these conditions, liposomes were nearly spherical with average encapsulation efficiency of (70.27±0.58)%, particle size of (22.9±6.8)nm and Zeta potential of (-29.79±1.24)mV, they were stable under 4 ℃ for 2 weeks. Conclusion: This optimized preparation technology is rational and stable, which can help to improve absorption and prolong effective time.