Formulation, Optimization and Evaluation of Solid Dispersion of Deferasirox Using Factorial Design

Abstract

Deferasirox, an oral iron-chelating agent, is a poorly soluble drug (Biopharmaceutical Classification System class II) having insufficient solubility in physiological fluids resulting in low bioavailability of the drug. The idea behind the present study was to explore the prospects of solid dispersion as a prolific method to enhance the dissolution rate of drug using a water soluble polymer. The solid dispersion was prepared by the solvent evaporation technique using Polyvinyl pyrrolidone with different drug to carrier and solvent ratio. Formulations were characterized through attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD), and in vitro release studies. A 32 factorial design was implemented to obtain optimum solubility, % yield, and optimization of solid dispersion (SD) also quantitates the influence of PVP on the solubility and dissolution profile. Thedrug-to-carrier and solvent ratio was chosen as independent variable, while %yield, drug content, and saturation solubility were chosen as dependent variables. The results showed that the optimized formulation of SD-DFX was able to significantly enhance its solubility. The SD containing a dispersion of Deferasirox with PVP show an exceptional rise in the solubility. This study describes the development of solid dispersion that significantly improved the solubility and bioavailability of DFX. The FTIR studies indicate the interaction between the drug and polymer. The DSC and XRD analysis indicated that the drug was in an amorphous state when dispersed in the polymer. It is resolved that the SD method significantly improves the solubility and dissolution rate, which could also be exploit for other poorly water soluble drug candidates. Keywords: Deferasirox , Polyvinyl pyrrolidone, solid dispersion, Factorial design, Solubility