维生素K1磷脂/胆盐混合胶束的制备及体外评价

Preparation and Characterization of Vitamin K Sodium Deoxycholate /Phospholipids-mixed Micelles

制备维生素K1磷脂/胆盐混合胶束(VK1 MMS),并进行体外评价。用薄膜分散-超声法制备维生素K1磷脂/胆盐混合胶束。通过单因素考察,对蛋黄卵磷脂(EPC)/甘氨胆酸钠(BS)的比例、胆盐浓度、超声时间进行筛选优化,测定维生素K1磷脂/胆盐混合胶束的粒径、形态;并分别考察混合胶束考察与0.9%氯化钠注射液或5%葡萄糖注射液的稀释稳定性。当胆盐浓度为55 mg/m L,磷脂/胆盐质量比为1,超声温度为40℃时,维生素K1磷脂/胆盐混合胶束的载药量达到5 mg/m L;混合胶束平均粒径为20.9 nm,形态为类球体,具有良好的稀释稳定性。维生素K1混合胶束的制备工艺简单方便、载药量高、粒径分布理想、稳定性好,可用于开发静脉注射制剂。

The aim of present investigation is to prepare vitamin K sodium deoxycholate /phospholipids-mixed micelles and then characterize the products by in vivo evaluation,the film dispersion-ultrasound method was used to prepare Vitamin K1 mixed micelles（ Vk1 MMS）.A optimized formulation was obtained by screening several factors affected on the formation of Vk1 MMS,including bile salts concentration,EPC / BS ratio,and ultrasound time.Then the obtained Vk1 MMS was characterized by investigation of particle size distribution,morphology and physically compatibility with 0.9% Na Cl or 5% glucose injections.The formulations with drug load of 5 mg / m L was prepared under such optimized conditions including EPC / BS ratio of 1,bile salts concentration of 55 mg / m L and ultrasound temperature of 40 ℃.The obtained Vk1 MMS possessed an average size of 20.9 nm and a globoid shape observed by transmission electron microscope（ TEM）,and was physically compatible with 0.9% Na Cl or 5% glucose injections.VK1 MMS,prepared by simple and convenient method,significantly enhanced the water solubility of VK,and had improved stability and safety,thus,could be used for intravenous injection in clinic.