Design of experiment approach in development of febuxostat nanocrystal: Application of Soluplus® as stabilizer

Abstract

The objective of present study was to explore the application of Soluplus® as a stabilizer for the preparation of febuxostat (FEB) nanocrystals using ball milling technique. Preliminary trials were performed for the selection of stabilizer fromHPMCVLV, PVA, PVP K30, Poloxamer 188 and Soluplus®. Soluplus®stabilized FEB nanocrystals were found stable and had least particle size as compared to the batches prepared using other stabilizers. A systematic optimization of critical process parameters, stirring time and amount of bead, of ballmilling process was performedwith aid of central composite design. Particle size (D50 and D90) and the size distribution (SPAN)were taken as responses for the evaluation of design batches and were used as the criteria for selection of optimized batch. Optimized formulation was characterized using SEM, XRD and DSC, depicted conversion of crystalline FEB into amorphous form having 26.08 times (in pH 1.2) and 1.67 times (in pH 6.0) more saturation solubility. In vitro drug dissolution study showed 9 times faster drug release while in vivo pharmacokinetic study showed an increase in oral bioavailability, Cmax and AUC, of FEB nanocrystals as compared to FEB API. Thus, current study supports the suitability of Soluplus® as stabilizer for the preparation of FEB nanocrystals.