Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect

초록

BackgroundCarvedilol, the anti-hypertensive drug, has poor bioavailability when administered orally. Ethosomes-mediated transdermal delivery is considered a potential route of administration to increase the bioavailability of carvedilol. The central composite design could be used as a tool to optimize ethosomal formulation. Thus, this study aims to optimize carvedilol-loaded ethosomes using central composite design, followed by incorporation of synthesized ethosomes into hydrogels for transdermal delivery of carvedilol.ResultsThe optimized carvedilol-loaded ethosomes were spherical in shape. The optimized ethosomes had mean particle size of 1301.72 nm, entrapment efficiency of 99.122.96%, cumulative drug release of 97.89 +/- 3.7%, zeta potential of - 31 +/- 1.8 mV, and polydispersity index of 0.230 +/- 0.03. The in-vitro drug release showed sustained release of carvedilol from ethosomes and ethosomal hydrogel. Compared to free carvedilol-loaded hydrogel, the ethosomal gel showed increased penetration of carvedilol through the skin. Moreover, ethosomal hydrogels showed a gradual reduction in blood pressure for 24 h in rats.Conclusions Taken together, central composite design can be used for successful optimization of carvedilol-loaded ethosomes formulation, which can serve as the promising transdermal delivery system for carvedilol. Moreover the carvedilol-loaded ethosomal gel can extend the anti-hypertensive effect of carvedilol for a longer time, as compared to free carvedilol, suggesting its therapeutic potential in future clinics.

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