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

Abstract

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/cm²/h and 0.416 ± 0.05 μg/cm²/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.

Keywords::

• Transdermal
• carvedilol
• polyvinyl pyrrolidone
• ethyl cellulose
• antihypertensive
• histocompatibility
• bioavailability

The authors thank A.I.S.S.M.S. College of Pharmacy, Pune, for allowing to carry out the project work throughout the year. Authors also thank Lupin Pharmaceutical Ltd, Pune for providing the carvedilol as a gift sample. Special thanks to Omega Laboratories, Pune for their help in carrying out the histopathology study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.