氧化苦参碱磷脂复合物自乳化释药系统的研制

Development of self-emulsifying drug delivery system for oxymatrine phospholipid complex

目的制备氧化苦参碱(OMT)磷脂复合物(PC)自乳化释药系统(OMT-PC-SEDDS),并对其进行质量评价及体外释放度考察。方法通过伪三元相图的绘制,以乳化区域面积为指标,筛选处方中乳化剂、助乳化剂种类及混合乳化剂比值(K_m),以溶解度大小考察油相种类,确定最佳处方;并对OMT-PC-SEDDS的外观、平均粒径、自乳化时间、体外释放特性及稳定性进行评价。结果 OMT-PC-SEDDS最佳处方为乳化剂Kolliphor HS 15与助乳化剂乙醇质量比为2∶1,中链甘油三酯(MCT)与Kolliphor HS 15和乙醇的总质量的质量比为2∶8。制备得到的OMT-PC-SEDDS外观呈澄明液体,稳定性良好,加水稀释后形成浅乳白色并带淡蓝色乳光的乳液,透射电子显微镜(TEM)观察呈类球形,分布均匀;平均粒径为(355.00±19.50)nm,Zeta电位为(-12.80±0.66)mV。在pH 6.8磷酸缓冲液中,OMT、OMT-PC和OMT-PC-SEDDS的体外释放在4 h分别达到93.84%、88.39%、88.61%。结论考察所得最佳处方制备的OMT-PC-SEDDS粒径适宜,稳定性良好。

Objective To prepare oxymatrine（OMT） phospholipid complex（PC） self-emulsifying drug delivery system（OMT-PCSEDDS）, and evaluate its quality and release in vitro. Methods The emulsifiers, co-emulsifiers and ratio of emulsifier to co-emulsifier（Km） were selected through the pseudo-ternary phase diagram method, using emulsified area as selection index, investigation of oil phase by solubility was determined to optimize the prescription. The appearance, average particle diameter, self-emulsification time, in vitro release characteristics, and stability of OMT-PC-SEDDS were evaluated. Results The optimum prescription of OMT-PC-SEDDS was emulsifier Kolliphor HS 15 and co-emulsifier ethanol mass ratio of 2∶1, the mass ratio of medium chain triglyceride（MCT） to the total mass of Kolliphor HS 15 and ethanol was 2∶8. The appearance of OMTPC-SEDDS was translucent clear liquid with good stability. OMT-PC-SEDDS diluted with water to form milky and pale blue emulsion. The emulsion was observed to be spherical by transmission electron microscopy and distributed evenly with average particle size of（355.00 ± 19.50） nm and Zeta potential of（-12.80 ± 0.66） mV. In pH 6.8 phosphate buffer, the in vitro release, the in vitro release of OMT, OMT-PC, and OMT-PC-SEDDS respectively reached 93.84%, 88.39%, and 88.61% at 4 h. Conclusion The prepared OMT-PC-SEDDS by optimum formulation of this study has a good particle size and good stability.