Transdermal therapeutic system of carvedilol: Effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics

The purpose of this research was to develop a matrix-type transdermal therapeutic system containing carvedilol with different ratios of hydrophilic and hydrophobic polymeric combinations by the solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells. The results followed Higuchi kinetics (r=0.9953−0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies, patches coded as F3 (ethyl cellulose: polyvinylpyr-rolidone, 7.5∶2.5) and F6 (Eudragit RL:Eudragit RS, 8∶2) were chosen for further in vivo studies. The bioavailability studies in rats indicated that the carvedilol transdermal patches provided steady-state plasma concentrations with minimal fluctuations and improved bioavailability of 71% (for F3) and 62% (for F6) in comparison with oral administration. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied using methyl prednisolone acetate—induced hypertensive rats. It was observed that both the patches significantly controlled hypertension from the first hour (P<.05). The developed transdermal patches increase the efficacy of carvedilol for the therapy of hypertension. Published; January 19, 2007