盐酸奈必洛尔-羟丙基-β-环糊精包合物的制备及表征  

Preparation and characterization of nebivolol hydrochloride HP-β-CD inclusion complexes

作　　者：周云[1,2] 符旭东 毕诗涛[1,2] ZHOU Yun;FU Xu-dong;BI Shi-tao(Department of Pharmacy, Wuhan General Hospital of People＇s Liberation Army of China, Wuhan 430070, China;Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China)

机构地区：[1]中国人民解放军武汉总医院药剂科,武汉430070 [2]湖北中医药大学药学院,武汉430065

出　　处：《中国新药杂志》2018年第8期954-959,共6页Chinese Journal of New Drugs

摘　　要：目的:制备盐酸奈必洛尔-羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrin,HP-β-CD)包合物,同时考察HP-β-CD提高盐酸奈必洛尔溶解度的效果。方法:应用溶液搅拌-冷冻干燥法制备包合物,采用L9(34)正交设计,以盐酸奈必洛尔与羟丙基-β-环糊精投料比(摩尔比)、包合温度、包合时间、乙醇浓度为因素,以包封率为指标筛选最佳工艺;通过相溶解度法、红外分光光度法和X-射线粉末衍射法对包合物进行验证;以高效液相色谱法(HPLC)测定包合物的包封率和溶解度。结果:最佳包合工艺为盐酸奈必洛尔与羟丙基-β-环糊精投料比(摩尔比)为1∶1,包合温度40℃,包合时间4 h,乙醇浓度80%(V/V);验证实验表明,盐酸奈必洛尔-羟丙基-β-环糊精包合物形成,相溶解度图呈AL型,物理混合物图谱与包合物图谱存在显著差别;以最佳工艺制备包合物,HPLC法测定其包封率达(73.69±0.10)%,药物经包合后在纯化水和p H 6.8磷酸盐缓冲液中的溶解度分别增大了3.18和11.10倍。结论:溶液搅拌-冷冻干燥法制备包合物方法合理可行,改善了药物的溶解性能。Objective：To prepare nebivolol hydrochloride hydroxypropyl-β-cyclodextrin（HP-β-CD）inclusion complexes,and investigate the improvement effect of HP-β-CD on the dissolution of nebivolol hydrochloride.Methods：The inclusion complex was prepared by solution-mixing and freeze-drying method and optimized by L9（34） orthogonal design with mole ratio of nebivolol hydrochloride to HP-β-CD,inclusion temperature,inclusion time and ethanol concentration as factors,using inclusion rate as evaluation index.Phase solubility method,infrared spectrophotometry（IR） and X-ray diffraction（XRD） were conducted to verify the inclusion complexes.The inclusion rate and dissolution were determined by HPLC.Results：The optimum inclusion process was as follows：the mole ratio of nebivolol hydrochloride to HP-β-CD was 1∶ 1,inclusion temperature was 40 ℃,inclusion time was 4 h,and ethanol concentration was 80%（V/V）.The verifying experiment indicated that nebivolol hydrochloride and HP-β-CD formed inclusion complexes,and phase solubility curve indicated ALtype.The analysis showed significant difference between the inclusion complexes and physical mixture.Under the optimal process,the inclusion rate of inclusion complexes were（73.69 ± 0.10） % as measured by HPLC.The solubility of the inclusion complexes were3.18 and 11.10 times higher than that of nebivolol hydrochloride in purified water and p H 6.8 phosphate buffer.Conclusion：Solution-mixing and freeze-drying method is reasonable and practicable to prepare inclusion complexes and it can improve the solubility of nebivolol hydrochloride.

关 键 词：盐酸奈必洛尔 羟丙基-Β-环糊精 环糊精包合 结构验证 溶解度 

分 类 号：R943[医药卫生—药剂学]