新型GPR40激动剂ADD-16及其钠盐平衡溶解度和油水分配系数的研究
Equilibrium solubility and oil-water partition coefficients of novel GPR40 agonist ADD-16 and its sodium salt
马丽莎 1林佳艳 1李琦 2郭凯蕾 3何金穗 3孙定康 3王庆伟 4刘雪英1
作者信息
- 1. 空军军医大学药学系,西安 710032
- 2. 河南大学生命科学学院,河南 开封 475004
- 3. 陕西中医药大学药学院,陕西 咸阳 712046
- 4. 西安秦皇医院,西安 710600
- 折叠
摘要
目的 测定ADD-16 及其钠盐形式在不同溶剂中的平衡溶解度及油水分配系数,为其后续的体内研究及制剂开发提供依据.方法 建立HPLC法定量测定ADD-16 及其钠盐含量,考察ADD-16 及其钠盐在不同有机溶剂和不同pH磷酸缓冲液中的平衡溶解度,测定ADD-16及其钠盐在正辛醇-水体系中的油水分配系数.结果 ADD-16 及其钠盐在醇类有机溶剂中的溶解度较高,尤其在极性较大的甲醇中溶解度最大,分别为 8.87、333.03 mg·mL-1.ADD-16 及其钠盐在磷酸缓冲液中的溶解度随pH增加而增大,均在pH 7.4 的缓冲液中溶解度最大,分别为6.63、796.86 μg·mL-1.ADD-16及其钠盐形式的油水分配系数分别为3.29、-0.45.结论 ADD-16 及其钠盐的溶解度均受溶剂极性及pH影响,ADD-16 成盐后溶解度有显著提高,且油水分配系数明显下降,ADD-16钠盐可能有更好的成药性.
Abstract
Objective To determine the equilibrium solubility and oil-water partition coefficients of ADD-16 and its sodium salt in different solvents,providing a basis for its subsequent in vivo research and formula development.Methods HPLC was used to detect the equilibrium solubility of ADD-16 and its sodium salt in different organic solvents and phosphate buffer solutions with different pH values.The method was also used to detect the oil-water partition coefficients of ADD-16 and its sodium salt in the n-octanol water system.Results The solubility of ADD-16 and its sodium salt in alcohol was high,especially in methanol,with the highest solubility of 8.87 and 333.03 mg·mL-1,respectively.The solubility of ADD-16 and its sodium salt in phosphate buffer increased with pH,and both have the highest solubility(6.63 and 796.86 μg·mL-1,respectively)in a pH 7.4 buffer.The oil-water distribution coefficients of ADD-16 and its sodium salt were 3.29 and-0.45,respectively.Conclusion The solubility of ADD-16 and its sodium salt is influenced by solvent polarity and pH value.After salt formation,the solubility of ADD-16 is obviously improved,and the oil-water distribution coefficient is decreased,indicating better drug formation performance of ADD-16 sodium salts.
关键词
GPR40/平衡溶解度/油水分配系数/高效液相色谱Key words
GPR40/equilibrium solubility/oil-water partition coefficient/HPLC引用本文复制引用
基金项目
陕西省创新能力支持计划(2021)(2021GCZX-07号)
陕西省秦创原"科学家+工程师"队伍建设项目(2023KXJ-080号)
出版年
2024
NETL
NSTL
万方数据