摘要
目的:制备酮洛芬磺丁基醚-β-环糊精包合物,以增加酮洛芬的溶出度和生物利用度。方法:通过研究酮洛芬与磺丁基醚-β-环糊精的平衡相溶解度,筛选主客分子的比例以及制备方法,以冷冻干燥法制备酮洛芬磺丁基醚-β-环糊精包合物。差示扫描热分析验证包合物的生成,测定包合物的包合率和含量,测定包合物中酮洛芬的溶出度和大鼠体内血药浓度并与原料酮洛芬做比较。结果:磺丁基醚-β-环糊精与酮洛芬的表观稳定常数为686.38 L·mol-1,两者是以摩尔比1∶1包合。包合物的包合率为(95.14±1.41)%,在0.1 mol·L-1盐酸中30 min的溶出度以达到90%,而酮洛芬只有35%,包合物在大鼠体内AUC0-∞为(28.6±8.54)μg·mL-1,而酮洛芬为(10.06±4.54)μg·mL-1。结论:使用磺丁基醚-β-环糊精制备包合物能增加酮洛芬的溶出度及提高生物利用度。
OBJECTIVE To prepare the inclusion compound with ketoprofen and sulfobutyl ether-β- cyclodextrin for improving the dissolution rate and bioavailability of ketoprofen. METHODS The ratio of ketoprofen and salfobutyl ether-β-cyclodex-trin and preparation methods were screened by phase solubility studies. The inclusion compounds were prepared by lyophiliza tion. The forming of inclusion compounds was validated by differential scanning calorimetry. The inclusion ratio and content of inclusion compounds were determined. In vitro dissolution rate and in vivo plasma drug concentration in rats were compared with those of bulk ketoprofen. RESULIN The stability constant （Kc） of phase solubility curve was 686.38 L. mol -1. The ketoprofen was included in sulfobutyl ethe-β-cyclodextrin with 1 ： 1 molar ratio. The inclusion ratio of inclusion compounds were （95. 14± 1.41 ）%. The ketoprofen in inclusion compound and bulk ketoprofen released after 30 min in 0. 1 mol. L -1 HCI were approximately 91% and 35%. AUG0-∞ of inclusion compound and bulk ketoprofen were （28.6±8.54）μg·mL-1 and （10.06±4.54）μg·mL-1, respectively. CONCLUSION Compared to the bulk ketoprofen, the inclusion compound with suI fobutyl etherfl3-cyclodextrin showed a substantial improvement in dissolution rate and bioavailability.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第20期1621-1625,共5页
Chinese Journal of Hospital Pharmacy
