PREPARATION AND CHARACTERIZATION OF POLYMETHACRYLATE-BASED MATRIX MICROSPHERES OF CARBAMAZEPINE USING SOLVENT EVAPORATION METHOD

The purpose of the present investigation was to prepare carbamazepine loaded Eudragit microspheres able to modify the release profile of carbamazepine by emulsion-solvent (R) evaporation technique. The effect of polymer, Eudragit (R) RSPO and Eudragit (R) RLPO alone and in combinations of these two acrylate polymers in different concentrations and in different drug polymer ratios on percentage yield, particle size, entrapment efficiency, and in vitro drug release behavior had been investigated. A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a 1:1 ratio and corn oil was selected as primary and secondary oil phases, respectively. Span 80 was used as the secondary surfactant for stabililizing the external oil phase. The solid state characterization was carried out by Fourier transform infrared spectroscopy, thermogravimetry, powder x-ray diffractometry, and differential scanning calorimetry. The surface morphology of microspheres was examined by scanning electron microscopy. Microspheres were found spherical and porous in nature. The mean particle size was between 20.74 - 29.33 mu m and the encapsulation efficiencies ranged from 52.61-67.39 %. The release profile and encapsulation efficiencies depended mainly on the structure of the polymers used as wall materials. The release rate of the Eudragit (R) RSPO microspheres was much lower than that of Eudragit (R) RLPO microspheres. The release pattern of carbamazepine in distilled water from different microsphere formulations and the commercial product (CP) was found to follow different kinetic models. The formulation (F1) was best explained by Higuchi's equation, formulations F2, F6, F7 and F8 confirmed that the release rates followed Hixson-Crowell cube root law, formulations F3, F4, F9 and commercial product (CP) followed zero order kinetic model of drug release, and the release from formulation F5 was best explained by Korsemayer-Peppas model. However, comparison of Akaike information criterion (AIC) values indicated first-order model for most of the formulations as the predominant release kinetics.