Enhanced oral bioavailability of 6-bromo-3-n-butylphthalide by self-nanoemulsifying system

Abstract

The objectives of this study were, first, to prepare 6-bromo-3-n-butylphthalide self-nanoemulsifying system (6-BBP-SNES); and second, to enhance the water solubility and oral bioavailability of 6-BBP. Pseudo-ternary phase diagram was constructed to identify an efficient self-emulsification region. Then, formulations were optimized by assessing the globule size and polydispersity. The composition of optimized 6-BBP-SNES was 6-BBP (10% w/w), Isopropyl myristate (40.5% w/w), Polyoxyethylene hydrogenated castor oil (36% w/w) and Absolute ethanol (13.5% w/w), with the globule size (80.50 ± 0.47 nm), polydispersity (0.150 ± 0.027) and an infinite dilution capability. In vitro drug release of SNES was above 80% within 5 min, whereas that of the suspension was less than 20%. Furthermore, the Cmax of 30 mg/kg of SNES after oral administration was 1.57-fold higher than that of 100 mg/kg of 6-BBP suspension. Besides, the absolute bioavailability of SNES was found to be 47.55%, whereas that of the suspension was only 8.73%, which increased by approximately 5.45-fold. These results demonstrated SNES could be promising to improve the oral efficacy of 6-BBP, and had potential clinical application value.