载蒿甲醚甘氨胆酸钠/大豆磷脂混合胶束的制备与稳定性评价

Preparation and stability evaluation of artemether-loaded mixed micelles composed of the sodium glycocholate and soybean lecithin

本研究采用薄膜分散法制备负载蒿甲醚(artemether,ARM)的甘氨胆酸钠(sodium glycocholate,SGC)/大豆磷脂(soybean lecithin,SL)混合胶束(mixed micelles,MM),考察了分散介质、SL质量比及辅料总浓度对ARM增溶的影响,并对MM的稳定性进行评价。结果表明,以磷酸盐缓冲液(PBS,pH 7.4,0.05 mol·L^(-1))为分散介质制备的SGC-SL-MM粒径分布均一[平均粒径3.58±0.14 nm,多分散系数(PDI)0.16±0.04],随着辅料总浓度从1.0%增加到30.0%(w/w),ARM的溶解度从0.64±0.04 mg·mL^(-1)显著增加到13.7±0.13 mg·mL^(-1)。阿伦尼乌斯(Arrhenius)参数及储存稳定性计算结果表明,无论37℃还是60℃,ARM在MM中的降解速率常数均小于乙腈-PBS(pH 7.4)溶液,呈现更好的稳定性。实验制备的ARM-MM在25℃储存2个月后溶液外观澄清,ARM含量降解小于7.0%。综上所述,本实验制备的SGC-SL-MM不仅可以提高ARM在水溶液中的溶解度,而且在低温时能提高其在水溶液中的化学稳定性。

In this study,artemether(ARM)-loaded mixed micelles(MM)composed of the sodium glycocholate(SGC)and soybean lecithin(SL)were prepared by film dispersion method.The effects of hydration medium,SL mass ratio and total concentration of excipients on the solubilization of ARM were investigated and the stability of MM was evaluated.Results showed that the particle size distribution of SGC-SL-MM prepared by phosphate buffer solution(PBS,pH 7.4,0.05 mol·L^(-1))was uniform,with an average size of 3.58±0.14 nm and the polydispersity index(PDI)value was 0.16±0.04.The solubility of ARM increased significantly from 0.64±0.04 mg·mL^(-1) to13.7±0.13 mg·mL^(-1) along with the concentration of total excipient increasing from 1.0%to 30.0%(w/w).The calculated results of Arrhenius parameter and storage stability showed that the degradation rate constant of ARM in MM was smaller than that in acetonitrile-PBS(pH 7.4)at either 37℃or 60℃.The experimental ARM-MM was clear after storing for two months at 25℃and the degradation of ARM was less than 7.0%.In conclusion,the SGC-SL-MM can not only improve the solubility of ARM in aqueous solution,but also improve its chemical stability in aqueous solution at low temperature.