Formulation,Characterization,and In Vivo Evaluation Of Febuxostat Ternary Solid Dispersion

Febuxostat?FEB?is a new,potent,non-purine selective inhibitor of xanthine oxidase which is used to treat hyperuricemia in adults with gout.FEB is classified as BCS class II drug and shows weak acidic?pKa³.08?nature.Because it is poorly aqueous soluble and vulnerable to enzymatic degradation.Therefore,it is urgent to enhance the solubility of FEB in water so as to improve the bioavailability of FEB.The objective of the present research was to prepare febuxostat?FEB?Ternary solid dispersion using a solvent evaporation method,and explore its effect on the saturation solubility,in vitro dissolution rate and oral bioavailability of FEB.In our present research,preliminary evaluations of certain amount of different ratios of FEB and carriers in the preparation of FEB solid dispersions.Preliminary trials were performed to select carrier among PEG4000,PEG6000,PVP K30,and Poloxamer.According to the resulting performance,for all polymers tested,when the drug/polymer ration was at 1?6,the solid dispersions performed best.And among all the tested polymers,PVP K30,Poloxamer188 and Poloxamer407 showed advantages over others.Since it is able to stabilize amorphous drugs and inhibit recrystallization during dissolution,the polyvinylpyrrolidone?PVP?,is one of the most widely used carriers for amorphous solid dispersion formulations.The literature investigation also showed the increase of dissolution rate and apparent improvement of solubility of the amorphous solid dispersion using Poloxamer,in comparison to crystallized drug compounds.Optimized Ternary solid dispersion composed of FEB,PVP K30 and Poloxamer at ratio of 1?3?3 was characterized using SEM,XRD,TGA,FT-IR and DSC.XRD and DSC evaluation indicated FEB was transformed from crystalline into amorphous state in solid dispersion and SEM images revealed the morphology.FT-IR suggested the interactions formed between FEB and polymers.A remarkable increase was observed of the optimized formulation in both saturation solubility and dissolution studies.Significant enhancement of oral bioavailability,C_max?18.25±2.44 vs.7.72±0.48?g/mL?and AUC_0-??53.62±7.63 vs.34.76±2.45?g·h/mL?was also observed in pharmacokinetic study.Thus,the present study supports the rationality of PVP K30 and Poloxamer188 as co-carriers for the preparation of FEB ternary solid dispersion.