Abstract
Poor solubility and appreciable first-pass metabolism have limited the oral bioavailability of nebivolol. The objective of the current investigation was to design, formulate, and optimize a hydrogel-based transdermal system for nebivolol using factorial design and compare its pharmacokinetics with oral suspension. Hydrogel formulations (F1–F8) were prepared by varying the amounts of gellan gum, carbopol, and polyethylene glycol. A 23 full factorial design was used to assess the effect of independent variables such as gellan gum, carbopol, and polyethylene glycol 400 on dependent variables like viscosity, in vitro release, and ex vivo permeation after 2 h at two levels. Optimized gel (F7), containing nebivolol hydrochloride (75 mg), gellan gum (300 mg), carbopol (150 mg), polyethylene glycol 400 (20 µL), tween 80 (1 mL), ethanol (10 mL), and water (up to 30 mL) was selected and evaluated in albino rats. The physicochemical properties of F7 (pH: 7.1 ± 0.15, viscosity: 8943 ± 116 centipoise, drug content: 98.81% ± 2.16%) seem ideal for transdermal application. It was noticed that the concentration of carbopol has a more significant role than gellan gum in gel viscosity. A biphasic release pattern was exhibited by gels, and the release rate was mainly influenced by the concentration of gellan gum. Greater transdermal flux (30.86 ± 4.08 µg/cm2/h) was observed in F7 as compared with other prepared gels. Noticeable enhancement in AUC0-α value (986.52 ± 382.63 ng.h/mL; p < 0.01) of transdermal therapy (~2-fold higher compared with oral administration) established the potential of F7 to improve the rate and extent of nebivolol delivery. The overall results demonstrated here signify that F7 could be a feasible alternative to oral therapy of nebivolol.
Highlights
Hypertension remains among the most serious health risks for millions of human populations.The World Health Organization’s (WHO) statistical report indicates that more than one billion people have been diagnosed with hypertension and estimated the increase in the global incidence to be ~60%more by 2025 [1]
It was observed that the gels prepared using hydroxypropyl methylcellulose were translucent and had more air entrapment and high viscosity as compared with gellan gum-containing gels
A systematic investigation was carried out to develop a transdermal system for effective delivery of nebivolol
Summary
Hypertension remains among the most serious health risks for millions of human populations.The World Health Organization’s (WHO) statistical report indicates that more than one billion people have been diagnosed with hypertension and estimated the increase in the global incidence to be ~60%more by 2025 [1]. Hypertension remains among the most serious health risks for millions of human populations. The World Health Organization’s (WHO) statistical report indicates that more than one billion people have been diagnosed with hypertension and estimated the increase in the global incidence to be ~60%. High blood pressure is the primary contributing cause of global mortality and kills millions of people yearly [2]. It is a well-documented fact that hypertension is identified with enhanced risk of cardiovascular diseases such as heart failure, myocardial infarction, and stroke. Lowering of blood pressure to normal values is the most important way of reducing cardiovascular risk.
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