注射用依匹哌唑缓释微球的体外释放度研究

In vitro release study of brexpiprazole sustained release microspheres for injection

目的:建立注射用依匹哌唑缓释微球的体外加速释放度方法,并探讨与体内释放的相互关系,为该制剂处方筛选和质量控制提供参考。方法:考察了释放介质中表面活性剂的种类和浓度、盐种类、温度等对释放行为的影响,通过区分能力和体内外关系(in vivo and in vitro relationship,IVIVR)分析最终确定了体外加速释放方法。结果:建立了45℃、pH 7.4的羟乙基哌秦乙硫磺酸(HEPES,含0.2%十六烷基三甲基溴化铵)的体外加速释放度方法,与体内释放具有良好的相互关系(r^(2)>0.99)。结论:本研究建立的体外加速释放度方法可以在药物开发的各阶段指导处方筛选以及工艺变更,对产品的质量控制具有重大意义。

Objective:To establish a method of accelerated release of brexpiprazole sustained release microspheres for injection in vitro and discuss the in vivo and in vitro relationship,so as to provide reference for prescription screening and quality control of this preparation.Methods:The effects of surfactant type,salt type and temperature on the release behavior were investigated by the method of constant temperature water bath.The in vitro accelerated release method was finally determined by the analysis of distinguishing ability and in vivo and in vitro relationship(IVIVR).Results:A method for accelerated release of pH 7.4 HEPES(containing 0.2%cetyltrimethylammonium bromide)at 45℃in vitro was established,which showed a good correlation with in vivo release(r^(2)>0.99).Conclusion:The method of accelerated release in vitro established in this paper can guide prescription screening and process modification in all stages of drug development,and it is of great significance for product quality control.