Phase behavior, intermolecular interaction and biopharmaceutical characterization of amorphous solid dispersion of febuxostat

Amorphous solid dispersions are an increasingly important formulation approach for drug delivery system utilized to enhance the drug delivery system by improving the aqueous solubility of poorly water soluble compounds. The aim of this work was to prepare and characterize the amorphous molecular dispersion of Febuxostat (FXT) using various polymers like poly(vinylpyrrolidone) (PVP K30), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), poly (vinylpyrrolidone-co-vinyl acetate) (PVP VA64). FXT, a non-purine selective inhibitor of xanthine oxidase which is used for the management of hyperuricemia in patients with gout, has been selected as poorly water-soluble model drug. The solid dispersions were prepared by solvent evaporation technique with different drug loading (3%, 10%, 15%, and 20%). Solid state characterization was evaluated by differential scanning calorimetry (DSC), X-ray diffraction study (XRD), Fourier transformation infrared spectroscopy (FTIR). DSC and XRD analyses indicated the complete transformation of FXT in the solid dispersion from crystalline to amorphous state. Each polymer was able to decrease the nucleation rate of amorphous FXT even at low concentrations (3- 10% w/w). Thermal analyses indicated that the glass transition temperature (Tg ) of the solid dispersion with all polymers showed an increase in T g as compared with FXT alone. Infrared spectroscopic studies indicated that hydrogen bonding interactions were formed between FXT and each of the polymers. These interactions were stronger between FXT and soluplus than for other polymers. Among the formulations, FXT solid dispersion with soluplus showed the highest saturation solubility.