β-环糊精及其衍生物对阿奇霉素的溶解度及溶出度的影响  

Influences of β-Cyclodextrin and Its Derivatives on Solubility and Dissolution of Azithromycin

作　　者：赵美荣[1] 杨华[1] 王立升[1] 

机构地区：[1]广西大学化学化工学院,广西南宁530004

出　　处：《中国医药工业杂志》2015年第8期837-842,共6页Chinese Journal of Pharmaceuticals

基　　金：广西科技攻关项目(桂科转14122008-15)

摘　　要：为提高阿奇霉素（1）的溶解度和溶出度,采用饱和溶液法制备1的β-环糊精（β-CD）或其衍生物（羟丙基-β-环糊精、甲基-β-环糊精和2,6-二甲基-β-环糊精）包合物,并以正交设计优化了包合工艺。熔点法、红外光谱、扫描电镜分析结果证实1被β-CD及其衍生物包合。考察了优化所得4种包合物的包合率、溶解度和溶出度。结果表明,包合物的溶解度和溶出度均显著高于1原药及物理混合物,但包合率偏低（55.6%~60.5%）。其中,2,6-二甲基-β-环糊精对增大1的溶解度和溶出度的效果最显著。25℃时1的2,6-二甲基-β-环糊精包合物的溶解度为1 016.5mg/ml,是原药（34.2mg/ml）的29.7倍;在pH 6.8磷酸盐缓冲液中180 min的溶出率约为90%。In order to improve the solubility and dissolution of azithromycin （1）, the inclusion complexes with β-cyclodextrin （β-CD） or its derivatives （hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin and 2,6-dimethyl- β-cyclodextrin） were prepared by saturated solution method, respectively. The inclusion process was optimized by orthogonal design. Moreover, the formation of inclusion complexes was verified by measuring melting point, infrared spectroscopy and scanning electron microscopy （SEM）. The inclusion rate, solubility and dissolution of four kinds of optimal inclusion complexes were investigated, respectively. The results showed that solubility and dissolution of four kinds of inclusion complexes were all significantly higher than those of bulk drug and the physical mixtures, but inclusion rates of these inclusion complexes were rather low （in the range of 55.6 % - 60.5 %）. Among these inclusion complexes, 2,6-dimethyl-β-cyclodextrin had the most significant impact on improving solubility and dissolution of 1. The solubility of inclusion complexes with 2,6-dimethyl-β-cyclodextrin were 1 016.5 μg/ml, which was 29.7 times higher than that of the bulk drug （34.2 μg/ml） ; the dissolution at 180 min in pH 6.8 phosphate buffer was about 90%.

关 键 词：阿奇霉素 Β-环糊精及其衍生物 包合物 增溶作用 溶出度 

分 类 号：R944.9[医药卫生—药剂学]