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

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 stability. The comparative study offers valuable guidance for the development of synergistic formulations of IM and CUR.