反溶剂沉淀-控温法制备黄体酮微晶

Preparation of progesterone microcrystals by antisolvent precipitationtemperature controlling method

目的制备一种新型的黄体酮缓释微晶注射剂,并考察微晶制备工艺参数对微晶粒径、形态及体外释放的影响。方法采用反溶剂沉淀-控温法制备黄体酮微晶,通过控制温度、时间及搅拌速度等工艺参数制备不同粒径的微晶。采用激光衍射法、扫描电镜(SEM)、X射线粉末衍射(XRPD)、取样分离等方法以及体外药物释放试验,表征微晶的粒径分布、形貌、晶型以及体外释放特性。结果分别制备了平均粒径为3.0、26.1和58.5μm的黄体酮微晶混悬液,SEM下观察微晶形状为棒状或立方体状,粒径均一。XRPD结果表明,不同粒径的微晶晶型无明显变化。体外释放测定结果表明,微晶的粒径分布与累积释放度存在良好的相关性,粒径越大,释放速率越慢。结论通过改变反溶剂沉淀-控温法的工艺参数得到不同粒径分布的黄体酮微晶,可控制药物的释放速度从而达到缓释目的。

Objective To prepare a new type of progesterone(PG)injection containing PG microcrystals with sustained release property,and investigate the effect of microcrystal-preparation process parameters on the mucrocrystal particle size,morphology and in vitro release.MethodsThe PG Microcrystals were prepared by the antisolvent precipitation-temperature controlling method(Anti-SPTC). The microcrystals with different particle size were prepared by controlling the process parameters such as the temperature,time and stirring speed. The particle size distribution,morphology,crystalline form and the in vitro release property of microcrystals were characterized by the laser diffraction,scanning electron microscope(SEM),X-ray powder diffraction(XRPD),sampling and separation methods as well as the in vitro drug release test.ResultsThe PG microcrystal suspensions with the average particle size 3.0,26.1,58.5 μm were prepared. The prepared microcrystals appeared to be clubbed or cuboidal shape,with a uniform particle size under SEM. The XRPD results showed that there was no significant changes in the crystalline form of the PG microcrystals with different particle size. Results of the in vitro release test indicated that the particle size of the PG microcrystals correlated well with the release rate of PG:The larger the particle size,the slower the release rate.ConclusionThe PG microcrystals with different particle size could be prepared by controlling the preparation process parameters in the Anti-SPTC controlling method,and the release rate of PG could be controlled by the use of different particle size PG mycrocrystals to achieve a sustained PG release.