他克莫司脂质微球注射液的制备  

Study of tacrolimus-loaded lipid microsphere preparation

作　　者：王月奇[1] 唐星[1] 蔡翠芳[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《中国药剂学杂志（网络版）》2014年第5期167-176,共10页Chinese Journal of Pharmaceutics：Online Edition

摘　　要：目的制备他克莫司脂质微球注射液并进行稳定性的初步评价。方法以外观、粒径及粒度分布、离心稳定性、ζ-电位、含量等作为主要评价指标,对他克莫司脂质微球注射液的处方及制备工艺进行了优化筛选,并进行初步稳定性的评价。结果最终处方及制备工艺确定为:将0.1 g他克莫司分散于溶有0.03 g油酸及1.6 g磷脂的15 g注射用油中,置磁力搅拌器中加热至75℃,并搅拌至全部溶解;将2.5 g甘油和0.2 g F-68分散于适量注射用水中,至磁力搅拌器中70℃加热搅拌使分散均匀得水相;在高速组织捣碎机搅拌下(10 000 r·min-1),将水相缓慢加入至油相中,待完全加入后,继续剪切4 min,得初乳;将初乳冷却至室温,转移至高压均质机中,以冰水浴控制均质温度在40℃以下,以80 000 kPa压力均质8次得终乳,以0.1 mol·L-1盐酸溶液将终乳pH值调节至6.0,用注射用水定容至全量;装瓶,封罐氮气,121℃高压蒸汽灭菌8 min,以冰水浴迅速降温即得。所制备的他克莫司脂质微球注射液样品的粒径和粒度分布、ζ-电位、含量、游离脂肪酸、甲氧苯胺值均符合规定标准,振摇稳定性良好,可用葡糖糖稀释,不可冷冻储存。结论可以将他克莫司制备成脂质微球注射液,且其初步稳定性良好。Objective To prepare and characterize tacrolimus lipid microsphere. Methods Formulation and preparation process of tacrolimus lipid microsphere were investigated using appearance, particle size, ζ-potential, pH, content and related substances of formulation as the evaluation index. Results The final formulation and preparation were optimized as follows: as mass percentage, the oil phase was composed of 0.1% tacrolimus, 1.6% lecithin, 0.03% oleic acid, and 15 % MCT; the water phase was composed of 0.2% F-68, 2.5% glycerol, and the oil phase and water phase were heated to 75 ℃ and 70 ℃ respectively; the homogenization pressure and cycles were 800 bar and 8 times; the pH was adjusted to 6.0 and then tacrolimus lipid microsphere was sterilized by autoclaving for 8 min at 121 ℃. The appearance, particle size, ζ-potential, pH, content, free fatty acids and methoxy aniline values meet the standards. The formulation can be diluted with glucose injection and it cann't be frozen. Conclusion Tacrolimus loaded lipid microsphere were successfully prepared with high preliminary stability.

关 键 词：药剂学 他克莫司 脂质微球 初步稳定性评价 

分 类 号：R94[医药卫生—药剂学]