Comparative Investigation on a Eutectic Mixture, Coamorphous Mixture, and Cocrystal of Imatinib and Curcumin: Preparation, Characterization, and Property Evaluation

作者：H. Li, Xiaomin Wang, Jinxia An, En Lin, Wei Li, Hai-Xin Qin, Jian-Feng Zhen, Xia-Lin Dai, Zhenjie Zhang, Tong‐Bu Lu, Jia‐Mei Chen · 发表于：Crystal Growth & Design · 年份：2025 · DOI：10.1021/acs.cgd.4c00926 · 被引用次数：6 · 研究领域：Synthesis and Characterization of Heterocyclic Compounds、Synthesis of Organic Compounds、Microwave-Assisted Synthesis and Applications

Multidrug solid systems (eutectic, coamorphous, and cocrystalline) offer potential to simultaneously improve both drugs’ properties. Yet, systematic comparisons of these forms for a given drug combination remain scarce. Imatinib (IM) and curcumin (CUR) demonstrate synergistic anticancer activity, and both are classified as BCS II drugs, characterized by poor solubility and bioavailability. Herein, a eutectic mixture (IM-CUR EM), coamorphous mixture (IM-CUR CM), and cocrystal (IM-CUR CC) involving IM and CUR were successfully prepared and fully characterized. Combined DSC and PXRD analyses revealed that IM-CUR CC exhibited an intermediate melting point and distinct diffraction peaks compared to individual components, whereas IM-CUR EM showed a lower melting endotherm with unchanged diffraction patterns. The amorphization of IM-CUR CA was verified by the absence of crystalline reflections (halo pattern) in the PXRD analysis and the presence of a single glass transition event in both DSC and modulated DSC thermograms. Crystal structure and FTIR analyses revealed strong intermolecular hydrogen bonding between the piperazine N of IM and phenolic O–H of CUR in both cocrystalline and coamorphous phases. Stability, dissolution and compaction performances, and anticancer activity were systematically evaluated. Notably, IM-CUR EM exhibited superior dissolution performance, while IM-CUR CA and IM-CUR CC showed an improved anticancer effect. All three solid forms exhibited excellent stab...