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Two Novel Co-Crystals of Naproxen: Comparison of Stability, Solubility and Intermolecular Interaction
Cheng Xing1, Ting Chen1, Li Wang1
1Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Abstract:
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.
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