Febuxostat suffers from relatively low bioavailability owing to the poor drug solubility and hepatic first-pass effect. This study aimed to prepare highly drug-loaded self-nanoemulsifying self-nanosuspension systems (SNESNS). SNESNS were designed to improve febuxostat's oral bioavailability by enhancing its solubility. Different oil and surfactant/co-surfactant mixtures were used for the preparation of SNESNS. The prepared SNESNS were estimated for their particle size, in vitro drug release and transmission electron microscopy (TEM). Results revealed that the oil mixture of Capryol™ 90:Miglyol® 812 (1:1 w/w) with surfactant/co-surfactant mixture of Cremophor® RH 40/Transcutol® HP loaded with drug in 4-fold greater concentration than its saturated solubility resulted in the formation of SNESNS by dilution under the effect of magnetic stirring. SNESNS were freeze-dried using trehalose as a cryoprotectant. TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Higher Cmax and AUC0-48 values compared to those of the market product Feburic® tablets confirmed the success of the SNESNS as a promising carrier for drugs suffering from poor water solubility like febuxostat.
Keywords: bioavailability; febuxostat; freeze-drying; high drug load; self-nanoemulsifying self-nanosuspension.