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

Febuxostat (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 C_max value (17.05 ± 2.6 µg/mL) compared to pure FBX C_max 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.

Materials

Febuxostat (M. wt., 316.37 g/mol) was kindly donated as a gift by Eva Company for Pharmaceutical Industries, Cairo, Egypt. Captisol®, Sulphobutyl Ether, 7, sodium salt β-cyclodextrin (SBE-βCD, M. wt., 2163 g/mol, purity 99.98%) was kindly supplied from Cydex Inc., USA. Disodium hydrogen phosphate, sodium dihydrogen phosphate, and methanol in the analytical grade were purchased from EL-Gomhoria Company, Egypt. Hydrochloric acid (35%) was purchased from El-Nasr Company, Egypt. Polyethylene glycol 6000 (PEG 6000) and PEG 4000 were purchased from Fluka (Germany). Hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) were also purchased from Sigma Chemical Company (St. Louis, USA). Distilled water was used during the studies. All other chemicals were of HPLC grade.

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Sakran, W., Abdel-Hakim, M., Teiama, M.S. et al. Febuxostat ternary inclusion complex using SBE7-βCD in presence of a water-soluble polymer: physicochemical characterization, in vitro dissolution, and in vivo evaluation. Drug Deliv. and Transl. Res. (2024).
https://doi.org/10.1007/s13346-023-01496-4