Comparison of enhancement of transdermal permeability of Carvedilol through physical and chemical methods

Background
The aim of the study was to overcome the difficulties raised in oral therapy; there is a need for the development of new drug delivery system that will improve the therapeutic efficacy. Because of its low dose and extensive hepatic metabolism, Carvedilol is a suitable candidate for transdermal administration.
Objective
The ultimate aim of this study was to administer Carvedilol through a transdermal patch and to evaluate by chemical method and iontophoresis by means of in-vitro drug release and ex-vivo permeation studies.
Materials and methods
The matrix type transdermal patches were prepared by solvent evaporation technique. Various formulations composed of hydroxypropyl methylcellulose (HPMC E15), Eudragit (ERL 100) in different ratios were prepared. All formulations consist of 15% v/w of dibutyl phthalate as plasticizer.
Results and conclusion
The prepared patches were characterized for various physicochemical parameters. The penetration-enhancing mechanism of iontophoresis was found to increase solvent flow through electro-osmosis and pore enlargement in the skin barrier, together with enhancement of electrochemical potential difference across the skin. The effect of chemical enhancer D-limonene and iontophoretic transdermal transport of drug using a current density of 1 mA/cm was investigated. Increasing the applied current density from 0.5 to 1 mA/cm resulted in a 2.2-fold increase in iontophoretic flux. Results demonstrated that iontophoresis exhibited a great ability to enhance the flux of drug in comparison with the chemical method. The optimized formulations F2 and F3 containing 8% D-limonene as chemical enhancer showed maximum skin permeation, 979.45 ± 3.16 and 900.57 ± 2.8 μg/cm, respectively, whereas formulations F9 and F10 with iontophoresis showed the skin permeation, 1048.7 ± 3.8 and 1476.7.7 ± 4.8 μg/cm, respectively, and obtained flux greater than F2.