依托度酸哌嗪盐的制备及其性能表征

Preparation and Characterization of Etodolac-Piperazine Salt

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。

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 O hydrogen 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.