应用化学 ›› 2020, Vol. 37 ›› Issue (1): 103-108.DOI: 10.11944/j.issn.1000-0518.2020.01.190185

• 研究论文 • 上一篇    下一篇

依托度酸哌嗪盐的制备及其性能表征

陈少东a,王晓娟b,李端秀b,王兆喜a,张海禄b*()   

  1. a上海大学理学院 上海 200444
    b中国科学院苏州纳米技术与纳米仿生研究所 江苏 苏州 215123
  • 收稿日期:2019-07-03 接受日期:2019-10-12 出版日期:2020-01-08 发布日期:2020-01-08
  • 通讯作者: 张海禄
  • 基金资助:
    国家自然科学基金(21874148)中国科学院青年创新促进会(2012242)和中国博士后科学基金会和中国科学院联合资助优秀博士后项目(2017LH045)资助

Preparation and Characterization of Etodolac-Piperazine Salt

CHEN Shaodonga,WANG Xiaojuanb,LI Duanxiub,WANG Zhaoxia,ZHANG Hailub*()   

  1. aCollege of Science,Shanghai University,Shanghai 200444,China
    bSuzhou Institute of Nano-Tech and Nano-Bionics,Chinese Academy of Sciences,Suzhou,Jiangsu 215123,China
  • Received:2019-07-03 Accepted:2019-10-12 Published:2020-01-08 Online:2020-01-08
  • Contact: ZHANG Hailu
  • Supported by:
    Supported by the National Natural Science Foundation of China (No. 21874148), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation and the CAS Jointly Funded Outstanding Postdoctoral Project (No. 2017LH045)

摘要:

制备了依托度酸和哌嗪的有机盐,并得到了其晶体结构。 结构解析结果表明,依托度酸羧基上的氢转移到哌嗪的氮原子上,N—H••••O氢键是维持结构稳定的主要分子间相互作用。 与原药相比,新合成的盐的本征溶出速率和平衡溶解度分别提高了2.1倍和4.8倍。 此外,新合成的盐具有良好的水合稳定性,在25 ℃,相对湿度95%的条件下暴露28 d未发生相变。作为依托度酸的第一个有机盐,该盐是依托度酸有前景的固体存在形式。

关键词: 依托度酸, 有机盐, 结构解析, 热分析, 水合稳定性, 溶解度

Abstract:

An organic salt of etodolac and piperazine was prepared and the crystal structure was obtained. Structural analysis indicated that a hydrogen proton transferred from etodolac carboxyl group to piperazine nitrogen atom. The N—H••••Ohydrogen bond was the main intermolecular interaction to maintain structural stability. The intrinsic dissolution rate and equilibrium solubility of the newly synthesized salt were increased by 2.1 times and 4.8 times, respectively, compared with the original etodolac. In addition, the newly synthesized salt has good hydration stability without phase transition for 4 weeks at 25 ℃ and 95% relative humidity. As the first organic salt of etodolac, the etodolac-piperazine salt is a promising new solid form of etodolac.

Key words: etodolac, organic salt, structure analysis, thermal analysis, hydration stability, solubility