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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 ketoprofen sulfobutyl ether-β-cyclodextrin inclusion complex to increase the dissolution and bioavailability of ketoprofen. Methods: By studying the equilibrium phase solubility of ketoprofen and sulfobutyl ether-β-cyclodextrin, screening the ratio of host-guest molecules and the preparation method, the ketoprofen sulfobutyl ether-β-cyclodextrin Inclusion compound. Differential scanning calorimetry was used to confirm the formation of inclusion complex. The inclusion rate and content of inclusion complex were determined. The dissolution of ketoprofen in inclusion complex and the plasma concentration of rat in vivo were determined and compared with ketoprofen. Results: The apparent stability constant of sulfobutylether-β-cyclodextrin and ketoprofen was 686.38 L · mol-1, both of which were encapsulated in the molar ratio of 1: 1. Inclusion complex inclusion rate was (95.14 ± 1.41)% in 0.1 mol·L-1 hydrochloric acid 30 min dissolution to reach 90%, while ketoprofen only 35%, inclusion complex in rats AUC0 -∞ was (28.6 ± 8.54) μg · mL-1, while ketoprofen was (10.06 ± 4.54) μg · mL-1. Conclusion: The preparation of inclusion complex with sulfobutyl ether-β-cyclodextrin can increase the dissolution and increase the bioavailability of ketoprofen.