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Open AccessArticle

Gellan Gum-Based Hydrogel for the Transdermal Delivery of Nebivolol: Optimization and Evaluation

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, UAE
Author to whom correspondence should be addressed.
Polymers 2019, 11(10), 1699;
Received: 17 September 2019 / Revised: 11 October 2019 / Accepted: 15 October 2019 / Published: 16 October 2019
(This article belongs to the Special Issue Pharmaceutical Polymers)
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. View Full-Text
Keywords: nebivolol; gellan gum; factorial design; gel; pharmacokinetics nebivolol; gellan gum; factorial design; gel; pharmacokinetics
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MDPI and ACS Style

Nair, A.B.; Shah, J.; Aljaeid, B.M.; Al-Dhubiab, B.E.; Jacob, S. Gellan Gum-Based Hydrogel for the Transdermal Delivery of Nebivolol: Optimization and Evaluation. Polymers 2019, 11, 1699.

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