New Cocrystals of\nthe Antihistamine Drug Bilastine\nwith Polyphenols: Structural Characterization and Solubility and Dissolution\nStudy

Six cocrystals of the antihistamine drug bilastine (BLN)\nwere prepared\nwith various phenolic coformers, namely, catechol (CAL), hydroquinone\n(HDQ), resorcinol (RES), pyrogallol (PYG), phloroglucinol (PHG), and\nresveratrol (RSV). The cocrystal structures were confirmed by single-crystal\nX-ray diffraction analysis and further characterized by spectroscopic\nand thermal methods. BLN-CAL crystallizes as an anhydrous cocrystal;\nBLN-HDQ (BLN-HDQ-H<sub>2</sub>O in 1:0.5:2), BLN-PHG (BLN-PHG-H<sub>2</sub>O in 2:2:4.625), and BLN-RSV (BLN-RSV-H<sub>2</sub>O in 2:1:4)\ncrystallize as cocrystal hydrates; and BLN-RES (BLN-RES-Ethanol-H<sub>2</sub>O in 2:3:1:1) and BLN-PYG (BLN-PYG-Ethanol-H<sub>2</sub>O\nin 1:1:1.5:1) crystallize as cocrystal hydrate ethanol solvates. The\nmelting point of the cocrystals is found to be in between BLN and\nthe respective coformers except for BLN-PHG. Hirshfeld surface analysis\nhas been implemented to show the intermolecular interactions present\nin the cocrystals. The solubility of BLN is found to be pH-dependent,\ni.e., 8015, 1525, and 340 mg/L in buffer pH 1.2, 4.6, and 6.8, respectively,\nat 37 ± 1 °C. The solubility result revealed that all of\nthe cocrystals except BLN-RSV showed increased solubility, nearly\n2-fold, in 1.2 pH buffer medium. At 4.6 pH buffer, the solubility\nfollows the order of BLN-RSV < BLN-HDQ < BLN-RES < BLN-CAL\n< BLN < BLN-PYG < BLN-PHG. At 6.8 pH buffer, BLN-PYG and\nBLN-PHG cocrystals showed the maximum improvement in solubility (6.5-\nand 3.5-fold improvement than BLN). The dissolution profiles at 37\n± 1 °C in 1.2 pH buffer exhibited a similar drug release\nprofile as compared to BLN, whereas at 6.8 pH buffer, the drug release\nis found to be slower in BLN-HDQ and BLN-RSV cocrystals.