肺靶向红霉素聚乳酸微球的研究

Study on the Erythromycin Polylactic Acid Microspheres for Lung Targeting

目的 用生物可降解材料聚乳酸 (PDLLA)制备肺靶向红霉素缓释微球 (ERY PDLLA MS)。方法 用正交设计优化微球制备工艺 ,用扫描电子显微镜观察微球表面形态 ,差示扫描热分析确证含药微球的形成。并对所制备的红霉素微球的粒径及其分布、载药量、包封率、工艺重现性、体外释药、稳定性及在体内各组织的分布进行了研究。结果 微球形态圆整 ,且药物确已被包裹在微球中 ,而非机械混合。微球的平均粒径为 11.18μm ,粒径在 5～ 2 0 μm占总数的 94 %以上 ,载药量为 2 4 .16 % ,包封率为 6 3.5 4 % ,最佳工艺条件重现性良好 ,微球在 4℃及 2 5℃放置三个月各方面性质稳定 ,体外释药符合Higuchi方程Q =2 8.0 6 7+3.85 15t1/ 2 (r=0 .9834) ,动物体内实验表明 ,红霉素微球混悬剂较普通注射剂更聚集在肺组织。结论 微球制备工艺稳定 。

AIM\ The purpose is to optimize the preparation of sustained release microspheres of erythromycin using the biodegradable materials polylactic acid (PDLLA) for lung targeting. METHEDS\ The orthogonal test design was used to optimize the technology of preparation with good reproducibility. The surface morphology of the microspheres was observed by scanning electron microscope. The formation of the drug microspheres was confirmed with DSC. The mean diameter and the size distribution of microspheres, the drug loading,the incorporation efficiency,the reappearances of pharmaceutical technology,drug release \%in vitro\%, stability and tissue distribution after intravenous administration were examined. RESULTS\ Erythromycin polylactic acid microspheres were regular in their morphology. Drug was enveloped in microspheres but not physically mixed with PDLLA. The average particle size was 11.65 μm with over 94% of the microspheres being in the range of 5~20 μm;the drug loading and the encapsulated ratio were 18% and 60% respectively. The reappearance of pharmaceutical technology was good. The microspheres were stable for three months at 4℃ and room temperature. The \%in vitro\% release properties could be expressed by the Higuchi′s equation: \%y=28.067+3.8515t\+\{1/2\} (r\%=0.9834). Compared with injective solution, the drug in microspheres was more concentrated in lung tissue. CONCLUSION\ The technology of preparation was successful and erythromycin polylactic acid microspheres showed significant sustained release and lung targeting.