Phenytoin sodium microcapsules: bench scale formulation, process characterization and release kinetics.

Abstract

The objective of this investigation was to formulate and prepare sustained-action microcapsules of phenytoin sodium (diphenyl hydantoin sodium salt). Using ethylcellulose and methyl acrylic acid copolymers (Eudragit S-100 and L-100) as coating materials, microcapsules of phenytoin sodium were formulated by an organic phase separation and a granule coating method. The phase diagrams were used to study the phase separation in an ethylcellulose-petroleum ether-toluene system, and the effect of temperature and amount of petroleum ether on the ethylcellulose left in the organic solvent mixture was investigated. The phase diagrams showed that increase in temperature did not significantly affect the ethylcellulose residue, and 60 ml of nonsolvent was found adequate for microencapsulation. In vitro release of the formulated microcapsules and the commercially available preparations was performed in CO2-free distilled water using the USP XXIII rotating basket method, and the profiles were evaluated by Higuchi kinetics. Geometric mean diameters of the microparticles prepared by two different methods showed differences due to different core:wall ratios. A 4 x 5 factorial design was utilized and multiple regression was applied to the dependent variables (ethylcellulose content, percent dissolved) against the independent variables (amount of nonsolvent, temperature, core:wall ratio); the optimum phenytoin sodium-to-ethylcellulose ratio was 1:2.3. Utilizing second-order polynomial equations, response-surface graphs and contour plots pointed out the time necessary for 40%, 55%, and 70% release of phenytoin sodium. The desired release profiles were obtained with formulations E-5, ES-2 and ESL-2.