环孢素脂质体的制备工艺与质量评价

Study on technology of preparation and quality evaluation of cyclosporin liposome

目的制备环孢素脂质体并进行质量评价。方法用薄膜-超声分散法制备环孢素脂质体,以包封率为评价指标,正交设计法优化处方和工艺,用HPLC法测定环孢素的含量,并观察其形态、粒径和稳定性。结果用混合磷脂制备环孢素脂质体的最优处方是磷脂和胆固醇的质量比为4∶1,磷脂在水化介质中的浓度为3%,药物和磷脂的质量比为1∶40,水化介质为pH=7.4的磷酸盐缓冲液;最佳的工艺条件为水化温度45℃,水化时间30min,搅拌时间10min,超声时间2h。按该处方工艺制备的脂质体包封率为97.84%,98.2%的粒径为(32.65±5.46)nm。在4℃冰箱存放5个月后形态和粒径无明显变化,渗漏率为4.55%。结论制备的环孢素脂质体包封率高、粒径小、稳定性好。

A/M To investigate the preparation and quality evaluation of cyclosporirtliposome. METHODS Cyclosporin liposome was prepared with thin-film ultrasonic dispersion technology and was evaluated by encapsulation efficiency. The orthogonal experimental design was used to optimize the prescription and technology of preparation. The con- tent of cyclosporin was determined by HPLC. The form, particle diameter and stability of cyclosporin liposome were observed. RESULTS The best prescription and technology of preparation was that phospholipid： cholesterol was 4： 1 （ m/ m）, and the percentage of phospholipid was 3% （m/v）. Gyclosporin： phospholipid was 1：40（m/m）. Hydrating medium was phosphate buffer of pH = 7.4 and the hydrating temperature was 45℃. The hydrating time was 30 min and the stirring time was 10 min. The hypersound time was 2 h. The encapsulation efficiency of the optimized liposome was 97.84% and 98.2 percent of particle diameter was （32.65±5.46）nm. The form and particle diameter had no obvious change with leak rate of 4.55% for five months at 4℃ in refrigerator. CONCLUSION Cyclosporin liposome is obtained with high encapsulation efficiency, small particle diameter and good stability.