Guan Qigang, Chen Wei, Hu Xianming
Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Pharmaceutical, Shenyang Institute of Pharmaceutical Industry, Shenyang, People's Republic of China.
Drug Des Devel Ther. 2015 Feb 10;9:791-8. doi: 10.2147/DDDT.S76676. eCollection 2015.
A novel lovastatin (LVT)-loaded poly(lactic acid) microsphere suitable for oral administration was developed in this study, and in vitro and in vivo characteristics were evaluated.
The designed microspheres were obtained by an improved emulsion-solvent evaporation method. The morphological examination, particle size, encapsulation ratio, drug loading, and in vitro release were characterized. Pharmacokinetics studies were used to show that microspheres possess more advantages than the conventional formulations.
By using the emulsion-solvent evaporation method, it was simple to prepare microspheres and easy to scale up production. The morphology of formed microspheres showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the microspheres was 2.65±0.69 μm; the encapsulation efficiency was 92.5%±3.6%, and drug loading was 16.7%±2.1%. In vitro release indicated that the LVT microspheres had a well-sustained release efficacy, and ex vivo studies showed that after LVT was loaded to microspheres, the area under the plasma concentration-time curve from zero to the last measurable plasma concentration point and the extrapolation to time infinity increased significantly, which represented 2.63-fold and 2.49-fold increases, respectively, compared to suspensions. The rate of ex vivo clearance was significantly reduced.
This research proved that poly(lactic acid) microspheres can significantly prolong the drug circulation time in vivo and can also significantly increase the relative bioavailability of the drug.
本研究开发了一种适用于口服给药的新型载洛伐他汀（LVT）聚乳酸微球，并对其体外和体内特性进行了评估。
通过改进的乳化溶剂蒸发法获得设计的微球。对其形态、粒径、包封率、载药量和体外释放进行了表征。药代动力学研究表明微球比传统制剂具有更多优势。
采用乳化溶剂蒸发法制备微球简单且易于放大生产。形成的微球形态呈表面光滑的球形，无任何颗粒聚集。微球平均粒径为2.65±0.69μm；包封率为92.5%±3.6%，载药量为16.7%±2.1%。体外释放表明LVT微球具有良好的缓释效果，体外研究表明，LVT载入微球后，从零到最后可测血浆浓度点以及外推至时间无穷大的血浆浓度-时间曲线下面积显著增加，与混悬液相比分别增加了2.63倍和2.49倍。体外清除率显著降低。
本研究证明聚乳酸微球可显著延长药物在体内的循环时间，也可显著提高药物的相对生物利用度。
