Febuxostat ternary inclusion complex using SBE7-βCD in presence of a water-soluble polymer: physicochemical characterization, in vitro dissolution, and in vivo evaluation

Abstract

AbstractFebuxostat (FBX), a potent xanthine oxidase inhibitor, is widely used as a blood uric acid-reducing agent and has recently shown a promising repurposing outcome as an anti-cancer. FBX is known for its poor water solubility, which is the main cause of its weak oral bioavailability. In a previous study, we developed a binary system complex between FBX and sulfobutylether-β-cyclodextrin (SBE7-βCD) with improved dissolution behavior. The aim of the current study was to investigate the effect of incorporating a water-soluble polymer with a binary system forming a ternary one, on further enhancement of FBX solubility and dissolution rate. In vivo oral bioavailability was also studied using LC–MS/MS chromatography. The polymer screening study revealed a marked increment in the solubility of FBX with SBE7-βCD in the presence of 5% w/v polyethylene glycol (PEG 6000). In vitro release profile showed a significant increase in the dissolution rate of FBX from FBX ternary complex (FTC). Oral in vivo bioavailability of prepared FTC showed more than threefold enhancement in Cmax value (17.05 ± 2.6 µg/mL) compared to pure FBX Cmax value (5.013 ± 0.417 µg/mL) with 257% rise in bioavailability. In conclusion, the association of water-soluble polymers with FBX and SBE7-βCD system could significantly improve therapeutic applications of the drug. Graphical Abstract