Compatibility Study and Solubility Enhancement of Febuxostat Using Box Behnken Design

Compatibility study (based on microenvironmental pH and isothermal stress testing) of Febuxostat was carried out with selected excipients (Microcrystalline cellulose (MCC), Mannitol, Lactose, Hydroxypropyl-β-cyclodextrin (HP-β-CD), Polyethylene glycol(PEG) 6000, Polyvinyl pyrollidoneK30, Eudragit EPO, Sodium starch glycollate, Croscarmellose sodium (CCMC), Sodium lauryl sulphate, Magnesium stearate (MgS), Sodium steryl fumarate, Aerosil 200 and Purified talc) using FTIR and HPLC. Among them, Aerosil 200, MgS, Purified talc, Lactose and MCC were selected for the formulation of Febuxostat tablet. Three different polymers viz. PEG 6000, HP-b-CD and CCMC were selected as independent variables to enhance the dissolution rate by their complexation. Fifteen formulations obtained from Box Behnken design (BBD) (Minitab 16) were prepared through kneading method. Contour plot suggested CCMC (13.01mg) and HP-b-CD (65.45mg) excluding PEG 6000 for optimized formulation. Drug release profile of optimized formulation compared separately with formulation without filler, without polymer, physical mixture and a marketed product using similarity (fs) and dissimilarity (fd) factors showed similarity with marketed product. Similarly, similarity and dissimilarity factors for formulation without filler and optimized formulation was obtained within the range (fs= 82.34 and fd=5.42) indicating that the filler does not have any effect on the drug release. fs and fd for formulation without polymer and physical mixture lied outside the range suggesting the importance of the polymer complexation in the formulation. An accurate, simple, precise and robust reversed-phase liquid chromatographic method was developed for the estimation of Febuxostat. Furthermore, solid state characterization evaluated by FTIR showed that complexation between the polymers has occurred in the optimized formulation.