Three indomethacin cocrystals: Preparation, characterization and formation thermodynamics

IF 3.7 3区工程技术 Q2 ENGINEERING, CHEMICAL

Chemical Engineering Research & Design Pub Date : 2025-05-13 DOI:10.1016/j.cherd.2025.04.048

Ying Zhang , Jingjing Liu , Ling Yin, Chengyun Yan, Bingli Jiang, Yueyi Deng

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Abstract

The cocrystals of Indomethacin (Imc) with isonicotine (Iso), isoniazid (Inh), and salicylic acid (Sa) were prepared to improve solubility, dissolution rate, and in vivo intestinal absorption. The prepared cocrystals were characterized by X-ray diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and Fourier infrared spectroscopy (FTIR). Subsequently, the equilibrium solubility and in vitro dissolution of the cocrystals were evaluated. The results indicate that the equilibrium solubility of the Imc-Inh cocrystal is 3.2 times that of Imc, and the maximum dissolution of the Imc-Iso cocrystal is approximately 4 times that of Imc. The mechanism underlying the formation of the Imc-Iso, Imc-Inh, and Imc-Sa cocrystals was investigated through the thermodynamics of the cocrystal formation and the calculation of DFT-D. The results demonstrate that the Gibbs free energy change (ΔG), the formation enthalpy change (ΔH) of the Imc cocrystals with Iso, Inh, and Sa are less than zero, indicating that the formation of cocrystals is spontaneous and driven by enthalpy. As the temperature rises, the values of ΔG of the cocrystals formation demonstrate a gradual increase, indicating that elevated temperatures are not favorable to cocrystal formation. In vivo single-pass intestinal perfusion experiments (SPIP) reveal that the Imc-Iso cocrystals can enhance the permeability of Imc.

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三种吲哚美辛共晶：制备、表征及形成热力学

制备吲哚美辛（Imc）与异烟碱（Iso）、异烟肼（Inh）和水杨酸（Sa）共晶，提高其溶解度、溶出率和体内肠吸收。用x射线衍射（XRPD）、差示扫描量热法（DSC）、热重分析（TG）和傅里叶红外光谱（FTIR）对制备的共晶进行了表征。随后，评估了共晶的平衡溶解度和体外溶出度。结果表明，Imc- inh共晶的平衡溶解度是Imc的3.2倍，Imc- iso共晶的最大溶解度约为Imc的4倍。通过共晶形成热力学和DFT-D计算，研究了Imc-Iso、Imc-Inh和Imc-Sa共晶的形成机理。结果表明：含Iso、Inh和Sa的Imc共晶的吉布斯自由能变化（ΔG）和生成焓变化（ΔH）均小于零，表明共晶的形成是自发的，由焓驱动。随着温度的升高，共晶形成的ΔG值逐渐增大，说明温度升高不利于共晶的形成。体内单次肠灌注实验（SPIP）显示Imc- iso共晶可以增强Imc的通透性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemical Engineering Research & Design 工程技术-工程：化工

CiteScore

6.10

自引率

7.70%

发文量

623

审稿时长

42 days

期刊介绍： ChERD aims to be the principal international journal for publication of high quality, original papers in chemical engineering. Papers showing how research results can be used in chemical engineering design, and accounts of experimental or theoretical research work bringing new perspectives to established principles, highlighting unsolved problems or indicating directions for future research, are particularly welcome. Contributions that deal with new developments in plant or processes and that can be given quantitative expression are encouraged. The journal is especially interested in papers that extend the boundaries of traditional chemical engineering.