Development and evaluation of carvedilol-loaded transdermal drug delivery system: In-vitro and in-vivo characterization study.

CONTEXT: The transdermal drug delivery system was prepared and the bioavailability of the selected drug was enhanced by reducing first-pass metabolism.
OBJECTIVE: The objective of this study was to enhance the bioavailability of carvedilol through transdermal patches.
MATERIALS AND METHODS: To develop a matrix-type transdermal patch containing carvedilol with different ratios of polymer combinations by solvent evaporation technique. RESULTS AND DISCUSSION: In-vitro permeation studies were performed by Franz diffusion cells. The results followed Higuchi kinetics, and mechanism of release was diffusion mediated. On the basis of the in-vitro and physicochemical parameters of carvedilol patches, the code F-1(PVP: Ethyl Cellulose = 4:1) was chosen for the study of in-vivo, ex-vivo, histocompatibility study, and pharmacological study. The bioavailability studies in rats indicated that the carvedilol-loaded transdermal patches provided steady-state plasma concentration and improved bioavailability of 72% in comparison to oral administration. The ex-vivo permeation study in rat's skin indicated that the flux and permeability co-efficient of optimized F-1 patch was 30.08 ± 0.7 μg/cm(2)/h and 0.416 ± 0.05 μg/cm(2)/h, respectively, which was more as compared to plain carvedilol. The histocompatibility study of the F-1 patch on the rat's skin after 24 h ex-vivo study gave less pathological changes as compared to other. The antihypertensive activity of the patch in comparison with oral administration was studied using N-nitro-L-arginine methyl ester-induced hypertensive rats. It was observed that the optimized patch (F-1) significantly controlled hypertension (p < 0.05).
CONCLUSION: The developed patch increases the efficacy of carvedilol through enhancement of bioavailability for the therapy of hypertension.