Box-behnken design: A statistical approach to evaluate the effect of crosslinked carboxymethyl cellulose and sodium starch glycolate on release kinetics of drug

Abstract

The aim of the study was to evaluate the release kinetics of domperidone maleate (DM) from immediate release (IR) tablets prepared by wet granulation method. Box-Behnken design (BBD) was used to optimize and evaluate the main, interaction and quadratic effects of independent variables i.e. crosslinked carboxymethyl cellulose (CMC) (X1), sodium starch glycolate (SSG) (X2) and starch (X3) on responses R2 of first order (YI) and β value of Weibull model (Y2). Prepared tablets were characterized by various physical tests, invitro drug release, Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). Accelerated stability studies were performed on optimized formulation D9. Y1 and Y2 were ranged from 0.9959 to 0.9994 and 0.041 to 0.912 respectively. β value of Weibull model indicated the parabolic shape of the dissolution curve. The quadratic model fits the data well and the resulting equations were used to predict the responses in the Box-Behnken design. FTIR spectra showed the compatibility of DM with CMC and SSG. XRD presented diffraction lines indicates crystalline nature of the drug. DSC thermograms indicated endothermic peak at 220 °C for DM. Stabilities studies revealed that no significant change in hardness, friability, disintegration time and dissolution release profile of DM. It is concluded that a combination of CMC and SSG can be used to enhance the dissolution and release kinetics of IR tablets of DM.