Bioavailability Enhancement of Nebivolol Hydrochloride Loaded Transferosomes via Transdermal Route: Pharmacokinetic and Pharmacodynamic Evaluation in Rats

Abstract

Background: Nebivolol hydrochloride is a beta blocker used to treat hypertension but has low oral bioavailability (12%) because of first-pass metabolism by CYP3A enzymes. Hence to improve bioavailability, nebivolol hydrochloride loaded transferosomes delivery via transdermal route is studied.Materials and Methods: Transferosomes were developed by thin film hydration method and evaluated for physicochemical properties. Study state flux was determined by permeability studies on excised rat abdominal skin using Franz diffusion cells. To evaluate the efficacy of transferosomes Pharmacokinetic and Pharmacodynamic studies were carried out on Wistar male rats.Results: Optimized transferosomal formulation TF2D comprises soya lecithin, tween80 and drug in the proportion 90:10:5 with 5% DMSO as permeation enhancer. The optimized formulation showed vesicle size 141.9 nm, PDI 0.143, Zeta potential -39.1 mV, entrapment efficiency 98.5% and steady state flux 97.4 μg/cm2/hr. The steady state flux of the TF2D was 4.23 times the flux of drug suspension. Scanning electron microscopic images displayed sphere shaped vesicles. FTIR studies confirm the compatibility between drug and formulation additives. Antihypertensive activity of TF2D was significantly high compared to oral drug suspension and the effect was sustained up to 48 hr. The bioavailability of TF2D was significantly high at p<0.0001 (4.13 folds) in comparison with oral drug suspension. The histopathological study on the rat skin confirmed the safety of the transferosomal formulation of nebivolol.Conclusion: We conclude that introducing transferosomes as vesicular drug carriers via transdermal route could significantly enhance the bioavailability of nebivolol hydrochloride.

Keywords: Nebivolol hydrochloride; Transdermal drug delivery; Transferosomes; Permeability studies; Pharmacodynamic activity; Pharmacokinetic activity