Quality by Design Approach for the Development of Self-Emulsifying Systems for Oral Delivery of Febuxostat: Pharmacokinetic and Pharmacodynamic Evaluation.

Abstract

The goal of the present investigation is to formulate febuxostat (FXT) self-nanoemulsifying delivery systems (liquid SNEDDS, solid SNEDDS, and pellet) to ameliorate the solubility and bioavailability. To determine the self-nanoemulsifying region, ternary plot was constructed utilizing Capmul MCM C8 NF® as an oil phase, Labrasol® as principal surfactant, and Transcutol HP® being the co-surfactant. Liquid SNEDDS (L-SNEDDS) were characterized by evaluating droplet size, zeta potential, % transmission, and for thermodynamic stability. In vitro dissolution study of FXT loaded L-SNEDDS (batch F7) showed increased dissolution (about 48.54 ± 0.43% in 0.1N HCl while 86.44 ± 0.16% in phosphate buffer pH7.4 within 30min) compared to plain drug (19.65 ± 2.95% in 0.1N HCl while about 17.61 ± 2.63% in phosphate buffer pH7.4 within 30min). Single pass intestinal permeability studies revealed fourfold increase in the intestinal permeability of F7 compared to plain drug. So, for commercial aspects, F7 was further transformed into solid SNEDDS (S-SNEDDS) as readily nanoemulsifying powder form (SNEP) as well as pellets prepared by application of extruder spheronizer. The developed formulation was found superior to pure FXT with enhanced oral bioavailability and anti-gout activity (with reduced uric acid levels), signifying a lipidic system being an efficacious substitute for gout treatment.