喷雾冷冻干燥技术制备盐酸伊立替康脂质体冻干微粒及其理化性质考察

目的:考察喷雾冷冻干燥(SFD)技术制备脂质体冻干微粒的可行性。方法:以盐酸伊立替康为模型药物,采用硫酸铵梯度法制备盐酸伊立替康脂质体,SFD技术制备脂质体冻干微粒;以喷嘴高度、物料流速、雾滴/液氮质量比为因素,应用Box-Behnk-enDesign(BBD)试验考察三者之间的配比对微粒包封率的影响以优化SFD工艺,并对所制备的脂质体及冻干微粒的理化性质进行了考察。结果:SFD优化工艺为物料流速5.5mL·min-1,喷嘴高度18.5cm,雾滴/液氮质量比3.7%,由此制备的脂质体冻干微粒的外观和再分散性好,平均粒径、粒度分布、主药含量及包封率等理化性质与原脂质体基本保持一致,且放置6个月后与原脂质体溶液比较稳定性更好。结论:SFD技术制备脂质体冻干微粒具有可行性,并提高了脂质体的稳定性。

Preparation of Irinotecan Hydrochloride Liposomal Lyophilized Microparticle by Spray-freeze Drying and Its Physico-chemical Characters

OBJECTIVE： To evaluate the feasibility of the preparation of Liposomal lyophilized microparticles by spray-freeze drying （SFD）. METHODS： Ammonium sulfate gradient method and SFD were adopted to prepare Irinotecan hydrochloride liposome （CPT-11 ） and liposomal lyophilized microparticles using irinotecan hydrochloride as active ingredient. Box-Behnken Design （BBD） was used to investigate the effect of the ratio of materials on the encapsulation coefficency of microparticles to optimize SFD using the height of spray nozzle, flow velocity and mass ratio of jet-atomized liquid drop to liquid nitrogen as factors. The physico-chemical characters of prepared liposome and liposomal lyophilized microparticles were analyzed. RESULTS： The optimized SFD technology was as follows： the flow velocity of material was 5.5 mL-min^-1; the height of spray nozzle was 18.5 cm; the mass ratio of jet-atomized liquid drop to liquid nitrogen was 3.7%. Prepared liposomal lyophilized microparticles were characterized with sound appearance and redispersibility. The particle size, distribution, main component and encapsulation coefficency of liposomal lyophilized microparticles were in line with those of liposome. Liposomal lyophilized microparticles exhibited better stability after 6 month of storage than liposome. CONCLUSION： The liposomal lyophilized microparticles can be prepared by SFD effectively, and the stability of liposome has been improved.