This work reports two novel drug–drug cocrystals of antifungal clotrimazole (CLT) with nonsteroidal anti-inflammatory drugs, including niflumic acid (NFA) and diclofenac (DIC). They were synthesized by slurry and solution crystallization methods and characterized by powder and single-crystal X-ray diffraction and differential scanning calorimetry. The cocrystals were found to have similar molecular packing, and to highlight their distinctness, the crystal lattice energies and intermolecular interaction energies were calculated by using the CLP-PIXEL software package. A series of competitive slurry experiments were carried out to qualitatively assess the thermodynamic stability of the cocrystals. The solubility, dissolution, and diffusion of the novel drug–drug cocrystals were investigated in a pH 1.2 buffer solution. There is a correlation between cocrystal stability and dissolution/diffusion behavior.
