Development of isosorbide dinitrate transdermal patch using crosslinked-chitosan as rate-controlling membranes

Abstract

The development of isosorbide dinitrate transdermal patch using crosslinked-chitosan as rate-controlling membranes was studied. Chitosan was blended with other hydrophilic polymers as polyvinyl alcohol with molecular weights of 30,000, 70,000 and 100,000, corn, potato or tapioca starches and subsequently, crosslinked with glutaraldehyde. In some crosslinked chitosan-starch membrane formulations, triacetin which was used as a plasticizer was added. Membranes were prepared by a casting technique. The physicochemical properties including physical characteristics, membrane morphology, percent water sorption, mechanical properties, crosslinking reaction and thermal property and the stability of these membranes were investigated. The membranes with good physicochemical properties and stability were selected to act as tate-controlling membranes in transdermal patches for skin permeation study. In permeation study, shed snake skin was used as a skin model. The obtained results showed that the physicochemical properties depended on type and the quantities of components in membrane formulations. The higher molecular weight of polyvinyl alcohol, the stronger membrane obtained. Increasing the amount of glutaraldehyde led to an increase in ultimate tensile strength and a decrease in percent water sorption. In crosslinked chitosan-starch membrane formulations, triacetin reduced both the brittleness of membrane formulations, triacetin reduced both the brittleness of membrane and percent water sorption. Moreover, high amount of low molecular weight of polyvinyl alcohol tended to give high porosity membrane and triacetin in crosslinked chitosan-corn starch membrane formulations gave pitted membrane surface. Using these two membranes as rate-controlling membranes in preparing transdermal patches could give high permeation rate closed to the permeation rate of commercial isosorbide dinitrate transdermal patch.