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

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.

Evaluation and Characterization of Tamarind Gum Polysaccharide: The Biopolymer

“…According to a study by Nair et al, the FTIR spectrum of nebivolol depicts characteristic peaks at 3209.93 cm −1 (O–H stretching), 2873.42 cm −1 (C–H stretching), 1491.67 cm −1 (C=C stretching), 1349.93 cm −1 (C–N stretching), and 1141.67 cm −1 (C–O stretching) [ 52 , 53 ]. Based on the literary facts the presence of IR bands at 3462, 3287, 3076, 2854, 1711 and 1498 cm −1 in FTIR spectrum of TGP were assigned to O–H, N–H, C–H, C=O stretch and C=C functional groups of the TGP [ 54 ]. The result of the IR spectral study was also supported by the study performed by Kailas et al and Chawananorasest et al [ 55 , 56 ].…”

Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies

“…Thus, for the optimization process using the design of experiments’ statistical technique, these three variables were selected as independent variables, and % drug release after 8 h and % EE were selected as dependent variables. A 2 3 full factorial design (Design Expert ® software, version 12, Stat-Ease Inc. Minneapolis, MN, USA) was applied [ 30 ] to check the effects of independent variables on dependent variables at two levels demonstrating low and high, respectively ( Table 1 ). The design formulation batches (D1–D8) representing independent variables with coded values and their levels are depicted in Table 1 .…”

Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box–Behnken Design and In Vitro Evaluation

“…The thermal behavior of terbinafine, PVP K30, and selected formulation (F8) was assessed using DSC (Hitachi DSC 7020, Tokyo, Japan). Weighted samples (5 mg) were kept in aluminum pans and secured non-hermetically, while a blank pan was taken as a standard reference during the study [ 41 ]. Thermograms were recorded at a particular heating rate (10 °C/min) under a nitrogen atmosphere with a heating range of 30–250 °C.…”