Factorial design-based optimization of the formulation of isosorbide-5-mononitrate microcapsules.

Abstract

Sustained action Isosorbide-5-mononitrate (IS-5-MN) microcapsules are prepared in order to overcome the tolerance developed in conventional preparations and to increase patient compliance. For this purpose, factorial design experiments are performed and microcapsules of IS-5-MN are formulated by the organic phase separation method using ethylcellulose with two different viscosities (10 and 45 cp) as coating material. The independent variables in the 2 x 3 x 3 factorial design are core: wall ratio, particle size and pH of the medium. The dependent variable, t50 percent is investigated by the second-order polynomial equation to establish the correlation between independent variables. By using the calculated equations, the response-surface graphs, from which various levels of independent variables could be predicted, are obtained. The in vitro release profiles of the formulated microcapsules and the commercially available preparations are obtained by using the rotating basket method. In vitro release is evaluated by zero-order, first-order, Hixson-Crowell and Higuchi release kinetics. The t50 percent values obtained from the Higuchi equation are used as response in the 2 x 3 x 3 factorial design experiments.