Abstract
Naproxen (NAP) is an aromatic propionic acid nonsteroidal anti-inflammatory drug, and vortioxetine (VOT) is a novel antidepressant drug. In this study, a new 1 : 1 drug-drug salt of NAP and VOT (namely, NAP-VOT) was designed and synthesized by liquid-assisted grinding and slow evaporation. The obtained salt was characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Single-crystal structure showed that NAP-VOT is a molecular salt. The NAP and VOT molecules in the salt were connected by N-H+⋯O hydrogen bonds between the carbonyl oxygen of NAP and the piperazine group of VOT. In addition, solubility and dissolution rate experiments were performed in water and pH 6.86 phosphate buffers, and the result suggested that salt formation could increase the solubility and dissolution rate of NAP and VOT in water. Furthermore, this study provides a new research idea to solve the problem of drug-drug combination by achieving drug-drug association at the molecular level.
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