超临界流体技术制备辛伐他汀/PLLA-PEG缓释复合微球  

Preparation of Simvastatin/PLLA-PEG Sustained-Release Microspheres by Supercritical Fluid Technology

作　　者：颜庭轩[1] 王志祥[1] 黄德春[1] 宋杏芳 

机构地区：[1]中国药科大学制药工程教研室,江苏南京210009

出　　处：《高校化学工程学报》2014年第2期401-406,共6页Journal of Chemical Engineering of Chinese Universities

基　　金：江苏省自然科学基金资助项目(BK2012763)

摘　　要：采用超临界流体(SCF)技术制备具有缓释效果的辛伐他汀/左旋聚乳酸(PLLA)-聚乙二醇(PEG)复合微球,以载药量和粒径为指标考察了结晶压力、结晶温度以及辅料浓度等操作参数对复合微球的影响。由单因素实验得到较优工艺条件为:结晶压力12 MPa,结晶温度45℃,PEG浓度6 mg?mL?1。在此工艺条件下制备得到的复合微球载药量为12.65%,粒径为6.24μm;通过红外(IR)、差示扫描量热法(DSC)以及扫描电镜(SEM)分析表明辛伐他汀可能与PLLA形成氢键结合,并以无定型形式复合于微球中;PEG均匀复合于微球骨架中。体外溶出实验表明辛伐他汀/PLLA-PEG缓释微球具有良好的缓释效果。实验结果表明,采用SCF技术可制备得到辛伐他汀/PLLA-PEG缓释微球,添加适量PEG可有效增加载药量,提高药物溶出速率。Simvastatin/Poly （L-lactic） （PLLA）-polyethylene glycol （PEG） sustained-release microsphereswere prepared by Supercritical Fluid （SCF） Technology. The effects of operating parameters, such ascrystallization pressure, crystallization temperature and PEG concentration on the loading of simvastatin and theparticle size of microspheres were investigated. The optimum conditions were obtained through single-factortests, which are： crystallization pressure 12 MPa, crystallization temperature 45℃, PEG concentration 6mg.mL-1. Under the optimal condition, the drug loading of the microspheres was 12.65% and the averageparticle size was 6.24 μm. Infrared spectrometry （IR）, differential scanning calorimetry （DSC） and scanningelectron microscopy （SEM） analysis indicate the presence of intermolecular hydrogen bonds betweenSimvastatin and PLLA in the microspheres, which results in the formation of amorphous drug forms. Moreover,PEG was evenly distributed in the microsphere skeleton. In vitro dissolution experiments show that themicrospheres had a good sustained-release effect. The experimental results demonstrate thatsimvastatin/PLLA-PEG can be prepared by SCF technology, and the addition of PEG can effectively increasedrug loading and improve drug dissolution rate.

关 键 词：超临界流体技术 辛伐他汀 聚乙二醇 左旋聚乳酸 缓释 

分 类 号：R94[医药卫生—药剂学]