DESIGN AND CHARACTERIZATION OF DONEPEZIL HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

Abstract

The ultimate aim of the present study was to develop sustained release (SR) tablets of Donepezil Hydrochloride by employing natural polymers (Guar gum and Xanthan gum) as the matrix material in different proportion by wet granulation method. Initially drug-excipients compatibility studies were carried out using FTIR and DSC which showed no interaction between drug and excipients. Granules of prepared batches were evaluated for bulk density, tapped density, carr’s index, hausner’s ratio, angle of repose. Tablets were evaluated for various physicochemical parameters like hardness, thickness, friability, weight variation test, drug content and in vitro drug release. All the formulation showed compliance with pharmacopoeial standards. 3 2 full factorial design was applied in which Guar gum (X 1 ) and Xanthan gum (X 2 ) were taken as independent factor and %CDR at 2hr (Y 1 ) and at 12hr (Y 2 ) were taken as response. In-vitro drug release study revealed that as the amount of polymers increased, % CDR decreased. Contour plots as well as response surface plots were constructed to show the effect of X 1 and X 2 on %CDR and predicted at the concentration of independent variables X 1 (40mg) and X 2 (40mg) for maximized response. The kinetic release treatment showed that korsmeyer peppas equation has shown of r 2 0.9517 which was close to one indicating that the dissolution profile fits in Korsmeyer-Peppas model and the mechanism of drug release from these tablets was by non-fickian diffusion mechanism. The optimized batch was kept for stability study at 40 ± 2 o C/ 75 ± 5 % RH for a period of 1 month according to ICH guidelines and found to be stable after 1 month of study. Keywords: Sustained release matrix tablet, Donepezil hydrochloride, Guar gum, Xanthan gum, 3 2 full factorial design.