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.
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.
Crystal data and structural refinement parameters of ETO-PIP
Hydrogen-bonding parameters of ETO-PIP
(A)Asymmetric unit of ETO-PIP; (B)Hydrogen bonding structure of ETO-PIP
The simulated and experimental PXRD patterns of ETO-PIP
DSC(A) and TG(B) curves of PIP, ETO and ETO-PIP
PXRD patterns of ETO-PIP and ETO after exposing at 95%RH/25 ℃ for 28 days
Curves of ETO-PIP and ETO used in intrinsic dissolution experiment
PXRD patterns of ETO-PIP and ETO after intrinsic dissolution experiment
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