School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
School of Functional food and Wine, Shenyang Pharmaceutical University, Shenyang, China.
Pharm Res. 2017 Oct;34(10):2211-2222. doi: 10.1007/s11095-017-2228-x. Epub 2017 Jul 24.
Progesterone (PRG) was selected as a model drug to develop a long-acting injection system for poorly water-soluble drugs.
Microspheres with high density-low porosity were prepared by hot-melt extrusion (HME) combined with wet-milling as the representative formulation, and a microcrystal suspension was also studied as a comparison. The morphology, particle size and distribution, polymorphism, drug distribution, density and porosity were characterized by scanning electron microscopy, laser diffraction particle size analyzer, power X-ray diffraction and DSC respectively. The in vivo performance of the different formulations within 7 days after intramuscular injection was evaluated in male SD rats.
The drug-loading rate of the microspheres could be as high as 40%. The average initial burst release of the microspheres (PLGA lactide:glycolide = 75:25) was only 6.7% much lower than that of the microsuspension (25.7%) and a sustained release was exhibited for at least 7 days. The release mechanism was speculated to be as follows. The microspheres are a drug depot with drug microcrystals in the PLGA matrix which is a layer by layer honeycomb structure.
Microspheres prepared by HME combined with wet-milling could achieve a long-term sustained release effect as a novel long-acting formulation strategy.
选择孕激素（PRG）作为模型药物，开发用于难溶性药物的长效注射系统。
采用热熔挤出（HME）联合湿磨法制备高密度-低孔隙度微球作为代表性制剂，并研究了微晶混悬液作为比较。通过扫描电子显微镜、激光衍射粒度分析仪、粉末 X 射线衍射和差示扫描量热法分别对形态、粒径及分布、多晶型、药物分布、密度和孔隙率进行了表征。在雄性 SD 大鼠中，评价了不同制剂在肌肉注射后 7 天内的体内性能。
微球的载药量可达 40%。微球（PLGA 丙交酯：乙交酯=75:25）的初始突释率平均仅为 6.7%，远低于微悬浮液（25.7%），至少可维持 7 天的缓释。推测释放机制如下。微球是药物储库，药物微晶体存在于 PLGA 基质中，呈层状蜂窝状结构。
HME 联合湿磨法制备的微球可作为一种新型长效制剂策略，实现长效缓释效果。
