Improved oral bioavailability of febuxostat by liquid self-micro emulsifying drug delivery system in capsule shells.

PURPOSE

Febuxostat is a non-purine xanthine oxidase inhibitor which belongs to the BCS class II. Main aim of this study is to enhance dissolution and bioavailability of a drug by formulating a liquid self-micro emulsifying drug delivery system (SMEDDS) in different capsule shells.

METHOD

Compatability of gelatin and cellulose capsule shells was checked with different oils, surfactants and co-surfactants. Solubility studies were then carried out in selected excipients. Capryol 90, labrasol, and PEG 400 were used in a liquid SMEDDS formulation based on phase diagram and the drug loading. Further SMEDDS was characterized for zeta potential, globule size and shape, thermal stability and in vitro release. Based on the in vitro release, pharmacokinetic study was carried out using SMEDDS in gelatin capsule shells.

RESULT

The diluted SMEDDS had globule size of 157.9±1.5d.nm, zeta potential of -16.2±0.4mV and they were thermodynamically stable. The formulation was found stable for 12 months in capsule shells. When tested in different media (0.1N HCl and pH 4.5 acetate buffer), the in vitro release of newly produced formulations differed substantially from that of commercially available tablets, while the release rate in alkaline medium (pH 6.8) was comparable and the highest. According to in vivo findings in rats, a threefold increase in plasma concentration, a fourfold increase in AUC, and a reduction in oral clearance increased fuxostat's oral bioavailability.

CONCLUSION

This investigation revealed that the novel liquid SMEDDS formulation sealed in capsules has considerable potential as a vehicle for enhancing the bioavailability of febuxostat.