FORMULATION DEVELOPMENT AND CHARACTRIZATION OF POLYSACCHARIDES MATRICES FOR MICROBIALLY TRIGGERED COLONIC DELIVERY OF MEBEVERINE HCL

Abstract

The objective of the present study was to develop and evaluate microbially triggered colon specific matrices of mebeverine Hcl using various polysaccharides like guar gum (GG), locust bean gum (LBG), psyllium husk (PH) and also xanthan gum (XG) to achieve higher drug release control. The tablets were prepared by both direct compression and wet granulation method. Pre-formulation and micromeritic studies of the drug, polymer & physical mixture were carried out. The matrix tablets were evaluated for their physico-chemical properties, in-vitro release (in presence and absence of rat caecal contents) and stability studies. The results of pre-formulation studies were in accordance with reported literature values. The prepared tablets were found to be uniform with respect to thickness (5.53 to 6.03 mm) and hardness (5.7 to 6.9 kg/cm2). The friability (0.41 to 0.95 %) and weight variation (1.04-1.66%) of different batch of tablets were found within prescribed limits. Drug content (96.01 to 99.89 %) was found uniform within the batches of different tablets. Swelling studies indicated that, matrix tablets prepared with XG alone (X4) and in combination with PH (PX4) swelled more as compared to those prepared using GG, LBG and PH. The order of swelling was XG>PH>GG>LBG for tablets prepared with single polymer and (XG+PH)> (XG+GG)> (XG+LBG) with combinations. Release profiles indicated that, increase in the polymer concentration has drastically retarded the release of mebeverine Hcl. Optimum release over a period of 24 hrs was obtained with drug polymer ratio of 1:1.5. Among the various polymers studied, XG gave better controlled release with alone (X4) and in combination with PH (PX4). In vitro release studies carried out in presence of rat caecal contents demonstrated the susceptibility of the polysaccharides towards colonic microflora and thereby triggering the drug release except XG. The mechanism of drug release was Non-Fickian diffusion controlled first order kinetics for optimized matrix tablets of GG (G4), LBG (L4) and XG+PH (PX4) where as for XG (X4) it followed Highuchi model. Stability studies indicated that the prepared tablets fairly remained stable during the one month stability period. FT-IR and DSC studies revealed the integrity of the drug in the formulations. Thus, the polysaccharide matrices can be efficiently prepared for the colonic delivery of mebeverine Hcl with the desired release profiles.