IN VITRO RELEASE KINETICS STUDY AND OPTIMIZATION OF AMBROXOL HCl 75 MG MATRIX TABLETS USING RESPONSE SURFACE METHODOLOGY

Abstract

The aim of the present study was the in vitro evaluation and optimization of Ambroxol HCl sustained release matrix tablets by response surface methodology.
The amounts of Methocel K4M and PVP K30 at three levels (-1, 0, +1) were selected as casual factors. In vitro dissolution time profiles at three different sampling times (1h, 4h, 8h) mean dissolution time (MDT) and time required for 50% drug release were selected as output variables . Thirteen kinds of Ambroxol HCl matrix tablets were prepared according to a 23 factorial design with five extra center points. The optimal tablet formulation based on some predetermined release criteria predicted by RSM was 80.28mg of Methocel K4M and 18.36mg of PVP K30. Dissolution studies were carried out in 900ml 0.1N HCl for 2 hours followed by 900 ml phosphate buffer (pH6.8) for subsequent 6 hours. Polynomial mathematical models, generated for various response variables using multiple linear regression analysis, were found to be statistically significant (p<0.05). The release mechanism was explored and explained by
zero order, first order, Higuchi’s and Korsmeyers’s equation. The drug release followed both diffusion and erosion mechanism in all cases. Calculated difference (f1 5) and similarity (f2 86) factors indicated that there was no difference between predicted and experimentally observed drug release profiles for the optimal formulation. It was concluded that optimization of Ambroxol HCl by Response Surface Methodology is quite efficient.