Two Novel Co-Crystals of Naproxen: Comparison of Stability, Solubility and Intermolecular Interaction.

Two novel co-crystals of naproxen (NPX) were designed and prepared at a stoichiometric ratio of 1:1, namely, naproxen-caprolactam (NPX-CPL) and naproxen-oxymatrine (NPX-OMT). The characteristics of the co-crystals were evaluated in terms of stability and solubility studies. In terms of solubility, in four kinds of solvent systems with different pH, the solubility of NPX-OMT was significantly improved compared with that of NPX, whereas the NPX-CPL showed advantages in acidic solvent systems, indicating that the co-crystals can be applied to concoct preparations depending on therapeutic purposes. Furthermore, the experimental results of the thermal analysis showed that the co-crystal NPX-OMT had better thermal stability than the co-crystal NPX-CPL. Finally, as a complement to the single crystal X-ray diffraction (SC XRD) method, the theoretical calculation based on density functional theory (DFT) was also used to reveal the intermolecular interaction of the co-crystals at the molecular level and visually display the difference between them.