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应用化学
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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 本期目录 | 过刊浏览 | 高级检索 |
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*()
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
Preparation and Characterization of Etodolac-Piperazine Salt
CHEN Shaodonga,WANG Xiaojuanb,LI Duanxiub,WANG Zhaoxia,ZHANG Hailub*()
aCollege of Science,Shanghai University,Shanghai 200444,China
bSuzhou Institute of Nano-Tech and Nano-Bionics,Chinese Academy of Sciences,Suzhou,Jiangsu 215123,China
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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。

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陈少东
王晓娟
李端秀
王兆喜
张海禄
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 wordsetodolac    organic salt    structure analysis    thermal analysis    hydration stability    solubility
收稿日期: 2019-07-03           接受日期: 2019-10-12
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
通讯作者: 张海禄     E-mail: hlzhang2008@sinano.ac.cn
引用本文:   
陈少东, 王晓娟, 李端秀, 王兆喜, 张海禄. 依托度酸哌嗪盐的制备及其性能表征[J]. 应用化学, 2020, 37(1): 103-108.
CHEN Shaodong, WANG Xiaojuan, LI Duanxiu, WANG Zhaoxi, ZHANG Hailu. Preparation and Characterization of Etodolac-Piperazine Salt. Chinese Journal of Applied Chemistry, 2020, 37(1): 103-108.
链接本文:  
http://yyhx.ciac.jl.cn/CN/10.11944/j.issn.1000-0518.2020.01.190185      或      http://yyhx.ciac.jl.cn/CN/Y2020/V37/I1/103
Scheme 1Molecular structures of (A)ETO and (B)PIP
Formula C34H52N4O6 γ 102.57(3)
Formula mass 660.86 V/nm3 0.9128(3)
T/K 293(2) Calculated density/(g·cm-3) 1.198
Crystal system triclinic F(000) 354
Space group P-1 Rint 0.0379
a/nm 0.5689(11) Number of parameters 229
b/nm 0.1138(2) Δρmaxρmin/(e·nm-3) 242/-188
c/nm 0.1495(3) GOF 1.076
α/(°) 97.64(3) R1[I>2σ(I)]/R1 0.0739/0.1103
β/(°) 100.78(3) wR2[I>2σ(I)]/wR2 0.2084/0.2432
表1ETO-PIP晶体数据和结构参数
Table 1Crystal data and structural refinement parameters of ETO-PIP
N—H••••O d(D―H)/nm d(H••••A)/nm d(D••••A)/nm ÐD—H••••A/(°)
N(1)—H(1)••••O(3) 0.086 0.212 0.281(6) 137
N(2)—H(2)••••O(2) 0.089 0.180 0.269(5) 175
N(2)—H(2D)••••O(2) 0.089 0.259 0.317(6) 124
N(2)—H(2D)••••O(3) 0.089 0.177 0.266(5) 179
表2ETO-PIP的氢键参数
Table 2Hydrogen-bonding parameters of ETO-PIP
图1(A)ETO-PIP的不对称单元;(B)ETO-PIP的氢键结构
Fig.1(A)Asymmetric unit of ETO-PIP; (B)Hydrogen bonding structure of ETO-PIP
图2ETO-PIP实验和模拟PXRD图谱
Fig.2The simulated and experimental PXRD patterns of ETO-PIP
图3PIP、ETO和ETO-PIP的DSC(A)和TG(B)图谱
Fig.3DSC(A) and TG(B) curves of PIP, ETO and ETO-PIP
图4ETO-PIP和ETO在95%RH/25 ℃条件下暴露28d的PXRD图谱
Fig.4PXRD patterns of ETO-PIP and ETO after exposing at 95%RH/25 ℃ for 28 days
图5ETO-PIP和ETO本征溶出曲线
Fig.5Curves of ETO-PIP and ETO used in intrinsic dissolution experiment
图6平衡溶解度实验后的ETO-PIP和ETO的PXRD图谱
Fig.6PXRD patterns of ETO-PIP and ETO after intrinsic dissolution experiment
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