Two Novel Drug-Drug Cocrystals of Antifungal Clotrimazole with Nonsteroidal Anti-Inflammatory Drugs

Thiswork reports two novel drug-drug cocrystals of antifungalclotrimazole (CLT) with nonsteroidal anti-inflammatory drugs, includingniflumic acid (NFA) and diclofenac (DIC). They were synthesized byslurry and solution crystallization methods and characterized by powderand single-crystal X-ray diffraction and differential scanning calorimetry.The cocrystals were found to have similar molecular packing, and tohighlight their distinctness, the crystal lattice energies and intermolecularinteraction energies were calculated by using the CLP-PIXEL softwarepackage. A series of competitive slurry experiments were carried outto qualitatively assess the thermodynamic stability of the cocrystals.The solubility, dissolution, and diffusion of the novel drug-drugcocrystals were investigated in a pH 1.2 buffer solution. There isa correlation between cocrystal stability and dissolution/diffusionbehavior. Two novel drug-drug cocrystalsof antifungal clotrimazolewith nonsteroidal anti-inflammatory drugs, including niflumic acidand diclofenac, have been obtained and thoroughly characterized usinga wide range of analytical techniques.

Automated summary

This study reports two novel drug-drug cocrystals of antifungal clotrimazole with nonsteroidal anti-inflammatory drugs, including niflumic acid and diclofenac. The cocrystals were synthesized using slurry and solution crystallization methods and characterized using various analytical techniques. The stability of the cocrystals was assessed qualitatively through competitive slurry experiments, and their solubility, dissolution, and diffusion were investigated in a pH 1.2 buffer solution.