Sustained-release from Layered Matrix System Comprising Chitosan and Xanthan Gum

ABSTRACT

Sustained-release tablets of propranolol HCl were prepared by direct compression using chitosan and xanthan gum as matrix materials. The effective prolongation of drug release in acidic environment was achieved for matrix containing chitosan together with xanthan gum which prolonged the drug release more extensive than that containing single polymer. Increasing lactose into matrix could adjust the drug release characteristic by enhancing the drug released. Component containing chitosan and xanthan gum at ratio 1:1 and lactose 75% w/w was selected for preparing the layered matrix by tabletting. Increasing the amount of matrix in barrier or in middle layer resulted in prolongation of drug release. From the investigation of drug release from one planar surface, the lag time for drug release through barrier layer was apparently longer as the amount of barrier was enhanced. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi's and zero order) was performed to study the drug release mechanism. Layering with polymeric matrix could prolong the drug release and could shift the release pattern approach to zero order. The drug release from chitosan-xanthan gum three-layer tablet was pH dependent due to the difference in charge density in different environmental pH. FT-IR and DSC studies exhibited the charge interaction between of NH₃⁺ of chitosan molecule and COO^? of acetate or pyruvate groups of xanthan gum molecule. The SEM images revealed the formation of the loose membranous but porous film that was due to the gel layer formed by the polymer relaxation upon absorption of dissolution medium. The decreased rate of polymer dissolution resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to ionic interaction between chitosan and xanthan gum. This was suggested that the utilization of chitosan and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.