New Cocrystals of the Antihistamine Drug Bilastine with Polyphenols: Structural Characterization and Solubility and Dissolution Study

Six cocrystals of the antihistamine drug bilastine (BLN) were prepared with various phenolic coformers, namely, catechol (CAL), hydroquinone (HDQ), resorcinol (RES), pyrogallol (PYG), phloroglucinol (PHG), and resveratrol (RSV). The cocrystal structures were confirmed by single-crystal X-ray diffraction analysis and further characterized by spectroscopic and thermal methods. BLN-CAL crystallizes as an anhydrous cocrystal; BLN-HDQ (BLN-HDQ-H2O in 1:0.5:2), BLN-PHG (BLN-PHG-H2O in 2:2:4.625), and BLN-RSV (BLN-RSV-H2O in 2:1:4) crystallize as cocrystal hydrates; and BLN-RES (BLN-RES-Ethanol-H2O in 2:3:1:1) and BLN-PYG (BLN-PYG-Ethanol-H2O in 1:1:1.5:1) crystallize as cocrystal hydrate ethanol solvates. The melting point of the cocrystals is found to be in between BLN and the respective coformers except for BLN-PHG. Hirshfeld surface analysis has been implemented to show the intermolecular interactions present in the cocrystals. The solubility of BLN is found to be pH-dependent, i.e., 8015, 1525, and 340 mg/L in buffer pH 1.2, 4.6, and 6.8, respectively, at 37 ± 1 °C. The solubility result revealed that all of the cocrystals except BLN-RSV showed increased solubility, nearly 2-fold, in 1.2 pH buffer medium. At 4.6 pH buffer, the solubility follows the order of BLN-RSV < BLN-HDQ < BLN-RES < BLN-CAL < BLN < BLN-PYG < BLN-PHG. At 6.8 pH buffer, BLN-PYG and BLN-PHG cocrystals showed the maximum improvement in solubility (6.5- and 3.5-fold improvement than BLN). The dissolution profiles at 37 ± 1 °C in 1.2 pH buffer exhibited a similar drug release profile as compared to BLN, whereas at 6.8 pH buffer, the drug release is found to be slower in BLN-HDQ and BLN-RSV cocrystals.