Enhanced Transdermal Delivery of Bisoprolol Hemifumarate via Combined Effect of Iontophoresis and Chemical Enhancers: Ex Vivo Permeation/In Vivo Pharmacokinetic Studies

Abstract

Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve® hydrogel (F7) showed a 1.5-fold increase in Q180, Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor® Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of Cmax and AUC0–40, respectively compared to Concor® tablets, as well as a smaller Tmax (2.00 ± 2.00 h). The relative bioavailability of F7 was found to be 201.44%, relative to Concor® tablets, demonstrating the significantly enhanced transdermal permeation of BH from the selected hydrogel by iontophoresis, in human volunteers. Finally, results showed the successful utility of permeation enhancers combined with iontophoresis in significantly enhanced transdermal permeation of BH, despite its large molecular weight and hydrophilic nature. Therefore, this strategy could be employed as a successful alternative route of administration to conventional oral tablets.

Transdermal Delivery of Telmisartan: Formulation, in vitro, ex vivo, Iontophoretic Permeation Enhancement and Comparative Pharmacokinetic Study in Rats

“…Generally, transdermal patches and gels are considered passive delivery techniques while microneedles, iontophoresis, sonophoresis, and ultrasound are considered enhanced delivery techniques. 10 Iontophoresis is a non-invasive physical method that can provide rapid delivery of drug molecules both locally and systemically, 11,12 involving the application of a low electrical potential gradient through the skin to improve molecular transport. However, Iontophoresis only improves small molecular drug transdermal delivery.…”

Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies

“…The pH of each formula was measured three times using a pH meter (3505–Jenway, Bibby Scientific Ltd., Dunmow, UK) and the average of the three values was calculated ( Teaima et al, 2021 ; Zafar et al, 2022 ).…”

“…For each of the investigated formulas, the individual rheological data [min, max, Farrow's constant (N), and hysteresis loop area (H.A)] were determined. To estimate the rheological behavior of each formula, the rheological data were evaluated using Farrow's equation ( Teaima et al, 2021 ) and Power law equation ( Ismail et al, 2020 ):…”

Transdermal delivery for gene therapy

“…Unfortunately, there are not many chemicals or chemical mixtures that have all these qualities. Some chemical enhancers are hydrogel patches [ 57 ], designed to work in concert with other TD methods (e.g., iontophoresis). Other enhancers are ionic liquids (salts that exist as a liquid at room temperature) [ 55 ] and deep eutectic solvents (mixture of H-bond donors and acceptors with a lowered melting point below room temperature) [ 58 ].…”