Transdermal potential and anti-gout efficacy of Febuxostat from niosomal gel

Abstract

Gout is a metabolic disorder which causes inflammation of the joints. The pain can be relieved by taking anti-inflammatory or pain-relieving medication. Febuxostat, a xanthine oxidase inhibitor is also used in the treatment of gout. It is a weak acid (pKa = 3.08) and is therefore, practically insoluble in water. Due to its limited solubility in water and susceptibility to enzymatic degradation in intestine and liver, its oral bioavailability is affected. The presence of food also decreases its maximum plasma concentration (Cmax) by 38–39%. Hence, transdermal route is preferred for its administration. In the present research, niosomal vesicles were selected for Febuxostat delivery because of their penetration enhancing ability. Niosomes containing Febuxostat were prepared using thin film hydration method. A 23 factorial design (DOE analysis) was carried out to reduce the number of experiments. Parameters contribution was determined using a 3-D response curve. Prepared optimized batch (F4) exhibited entrapment efficiency of 73.93 ± 0.75% and percent cumulative drug release of 83.03 ± 0.07%. Transmission Electron Microscopy (TEM) revealed vesicular, spherical particles with a smooth surface in the nano range. Niosomal gel of optimized batch (F4) was prepared incorporating 2% w/w carbopol 934. The ex-vivo permeation study was performed in the Franz diffusion apparatus using excised rat abdominal skin in phosphate buffer pH 7.4, which showed prolonged drug permeation of 80.37 ± 0.02%. In-vivo study of optimized Febuxostat niosomal gel NG (F4) on rabbits revealed better results than the standard (pure) Febuxostat. NG (F4) exhibited good stability throughout 90 days at different temperature and humidity.