摘要
目的测定Enmein的平衡溶解度、油水分配系数,考察环糊精对其包合作用,为制剂研究奠定基础。方法采用HPLC测定Enmein在不同溶剂中的平衡溶解度;采用摇瓶法测定Enmein在不同条件下的油水分配系数;以羟丙基-β-环糊精(HP-β-CD)、羟丙基-γ-环糊精(HP-γ-CD)2种材料制备Enmein包合物,经溶解度试验,比较溶解性能的变化。结果(25±0.5)℃振摇24h,Enmein在纯水中溶解度为(239.32±4.99)μg·mL-1,在多种常见的有机溶剂中微溶,在常用的药用油溶剂中不溶;正辛醇-水体系中,测得Enmein油水分配系数P为4.64,不同生理pH环境及环糊精材料,对其lg P影响不大;经过2种材料包合后,Enmein的溶解度有所提高,其中以HP-γ-CD的增溶效果最好。结论 Enmein在水、常见的药用油溶剂中溶解性均不好;消化道生理pH变化及包合材料对Enmein的吸收影响不大;用Enmein的HP-γ-CD包合物为原料制备制剂,有利于提高其生物利用度。
OBJECTIVE To determine the equilibrium solubility, oil/water partition coefficient and study the cyclodextrin inclusion complex of Enmein, provide the basis for the new preparation of Enmein. METHODS The equilibrium solubility of Enmein in different solvents were detected by HPLC. Flask shaking method was used to determine the oil/water partition coefficients of Enmein in different conditions. The Enmein inclusion complexes were prepared with HP-β-CD and HP-γ-CD. They were compared the change with solubility. RESULTS The equilibrium solubility of Enmein in water was（239.32± 4.99）μg·m L^-1 at（25±0.5）℃ for 24 h,it was slightly soluble in organic solvents, and insoluble in medical oils. The octanol-water partition coefficient of Enmein was 4.64. Different pH and cyclodextrins had little effect on lg P. The solubility of inclusion complexes were increased, in which HP-γ-CD was the stronger. CONCLUSION Enmein has poor solubility in water and medical oils, and its absorption is less influenced by different pH and cyclodextrins. The bioavailability is significantly increased when Enmein is included by HP-γ-CD.
作者
尚校军
王淑雨
卢慧娟
马素英
闫福林
SHANG Xiaojun;WANG Shuyu;LU Huijuan;MA Suying;YAN Fulin(Xinxiang Medical University,a.School of Pharmacy,b.School of International Education,Xinxiang 453003,China;The First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2018年第10期1447-1450,共4页
Chinese Journal of Modern Applied Pharmacy
基金
河南省教育厅高等学校重点科研项目(15A350010)
河南省科技攻关重点项目(122102310286)
关键词
Enmein
平衡溶解度
油水分配系数
环糊精
包合作用
Enmein
equilibrium solubility
oil/water partition coefficient
cyclodextrin
inclusion interaction
