去甲斑蝥素脂质体的制备工艺优化及其药剂学性质研究

Preparation Technique Optimization of Norcantharidin Liposome and Its Pharmaceutical Properties

目的:优化去甲斑蝥素脂质体的制备工艺,并对其药剂学性质进行评价。方法:以包封率、平均粒径及跨距为综合指标,分别考察4种制备方法即薄膜分散法、注入法、逆相蒸发法和逆相蒸发薄膜法对去甲斑蝥素脂质体包封率和粒径的影响;以磷脂的量(X1)、磷脂/胆固醇质量比(X2)、探头式超声次数(X3)、磷酸盐缓冲液稀释倍数(X4)、油水相体积比(X5)和脂类与药物的质量比(X6)为考察因素,采用均匀设计优化逆相蒸发薄膜法制备载药脂质体的制备工艺,并对最佳工艺进行验证试验。结果:以逆相蒸发薄膜法制备脂质体包封率最高;最佳工艺:X1为200mg、X2为7∶1、X3为20次、X4为50倍、X5为1∶4、X6为30∶1;验证试验中样品脂质体包封率为(42.5±1.3)%,平均粒径为(210.9±2.1)nm,跨距为0.61±0.12。结论:成功制备了去甲斑蝥素脂质体。

OBJECTIVE： To optimize the preparation technique of norcantharidin liposome（NL） and study its pharmaceutical properties. METHODS： With envelopment efficiency（EE）, mean particle size and span of the liposome as indexes, the effects of thin film dispersion method, injection method, reverse phase evaporation and reverse phase film - evaporation method on the EE and particle size of the NL were evaluated. And the uniform design was used to optimize the reverse phase film-evaporation preparation technique of NL with the amount of phospholipid （X1）, the mass ratio of phospholipid/cholesterol （X2）, the sonde-type uhrasounding times （X3）, the dilution times of buffer phosphate （X4）, the volume ratio of oil/ water phase （X5） and the mass ratio of lipoids/drug （X6） as integrated indexes. A verification test was performed on the optimal technique. RESULTS： The formulation prepared by reverse phase film-evaporation technique exhibited the best EE. The preparation conditions of the optimized NL were as follows： X1 = 200 rag; X2 = 7 ： 1; X3 = 20 times; X4 = 50 times; X5 = 1 ： 4; X6= 30 ： 1. The verification test showed that the EE, the mean particle size and the span of the liposome were （42.5± 1.3） %, （210.9±2.1） nm and （0.61 ±0.12）, respectively. CONCLUSION： NL was prepared successfully.