Enhancement of in vitro dissolution and in vivo performance/oral absorption of FEB-poloxamer-TPGS solid dispersion

Abstract

In the present study, a febuxostat (FEB) solid dispersion was prepared via the solvent evaporation method, and the dispersion's solubility, dissolution rate and oral bioavailability were investigated. To select the appropriate carriers for the FEB solid dispersion, series of preliminary trials were performed on d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), HPMC, PEG4000, PEG6000, Eudragital, PVA, PVP K30, poloxamer188 and poloxamer407. Based on the preliminary trials, TPGS and poloxamer188 were selected as the carriers for the FEB solid dispersion preparation. In addition, a mixture of FEB:poloxamer188:TPGS (1:5:1) exhibited outstanding characteristics; its saturation solubility was 7.31 times (in water), 17.67 times (in pH 1.2), 17.22 times (in pH 4.5), 3.60 times (in pH 6.0) and 1.99 times (in pH 6.8) higher than that of pure crystalline FEB. In an in vitro drug dissolution study, the mixture exhibited a drug release rate that was 1.94 times that of the FEB API. Meanwhile, oral bioavailability, Cmax and AUC, as evaluated in an in vivo pharmacokinetic study, also showed a notable enhancement.