艾塞那肽W/O/W复乳的处方工艺优化及性质考察

Formula and Preparation Optimization and Properties Study of Exendin W/O/W Multiple Emulsion

目的:对艾塞那肽复乳的处方及工艺进行优化,并评价其体外主要性质,为研发其长效制剂奠定基础。方法:以复乳产率及分离时间为综合评价指标,采用正交试验优化艾塞那肽复乳的处方及制备工艺。对其形态、粒径分布、稳定性、包埋率及体外释药特性进行考察。结果:最佳处方为:W1相与O相体积比为1∶1.2,乳化剂Ⅰ在O相中的质量浓度为10%,泊洛沙姆407在W2相中的质量浓度为10%,W1/O初乳与W2相的质量比1:1。最佳工艺为:初乳搅拌速度为10 000 r·min^(-1),初乳搅拌时间为10 min,复乳搅拌速度为2 500 r·min^(-1),复乳搅拌时间为3 min。艾塞那肽复乳形态圆整,平均粒径为(46.3±2.6)μm,离心稳定性及黏度稳定性均较好,包埋率高达90%以上,体外释药符合Higuchi方程Y=13.793 X+5.598(r=0.988 3),具有明显的缓释长效性。结论:艾塞那肽复乳处方及制备工艺简单,稳定性较好,具有明显的缓释性。

Objective ： To optimize the formula and preparation of exendin W/O/W multiple emulsion, and study the main proper- ties in vitro to lay foundation for the development of exendin prolonged action preparation. Methods： Using multiple emulsion yield and centrifugal separation time as the comprehensive index, the formula and preparation of exendin multiple emulsion were optimized by or- thogonal tests, and the morphology, particle size, stability, encapsulation efficiency and drug release in vitro were studied. Results： The optimal formula was as follows ： the volume ratio of W1 phase to O phase was 1： 1.2, the quality percentage of emulsifier I in the O phase was 10%, poloxamer 407 in W2 phase was 10% , and the quantity ratio of W1/O to W2 phase was 1： 1. The optimal prepara- tion conditions were as follows： the stirring speed for W1/O was 10 000 r min-l , and the stirring time was 10 min, and that for W1/ O/W2 was 2 500 r min -1 with the stirring time of 3 min. The multiple emulsion was spherical with the mean size of （46.3 ±2.6 ） μm, and the centrifugal and viscosity stability were both promising. The drug encapsulation efficiency was above 90%, and the drug release in vitro accorded with a Higuchi equation ： Y = 13. 7930X ＋ 5. 5981 （ r = 0.988 3 ）, showing notable sustained and prolonged property. Conclusion： The optimal formula and preparation process of exendin multiple emulsion are simple with high drug content, good stability and notable sustained release property in vitro.