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

Abstract

Purpose

The purpose of this study was to prepare telmisartan transethosomes, incorporate them into a gel, evaluate them for in vitro drug release and in vivo permeation using iontophoresis to enhance their transdermal delivery.

Materials and Methods

TE formulae were prepared using various surfactants (SAAs), different ethanol concentrations, and different phospholipid-to-SAA ratios with different cholesterol ratios, characterized according to their entrapment efficiency percentage (EE%), zeta potential (ZP), particle size (PS), and polydispersity index (PDI). The optimum three formulae were incorporated into a gel, evaluated physically, in vitro dissolution, and ex vivo drug permeation using rat skin and Iontophoresis was performed on the best formula.

Results

The optimum three formulae (F29, F31, F32) had an EE% of 97±0.26%, 89±0.25% and 88±0.17%, PS of 244±5.88 nm, 337±4.6 nm and 382.2±3.06 nm, PDI of 0.57±1.9, 0.5±1.4 and 0.63±2.2 and ZP of −31.6±1.59 mV, −28.3±3.79 mV and −31±5.65, respectively. Selecting F29 for in vivo study by iontophoretic enhancement, Cmax was increased by 1.85 folds compared to the commercial oral tablet and by 1.5 folds compared to transdermal gel. Tmax decreased by half using iontophoresis compared to commercial tablets and transdermal gel.

Conclusion

The transethosomal formulation of telmisartan enhanced its transdermal absorption and increased its bioavailability as well. Iontophoresis was used to increase maximum plasma concentration and reduce Tmax by half.

Keywords:

• telmisartan
• TEL
• entrapment efficiency
• EE
• transethosomes
• iontophoresis

Disclosure

The authors report no potential conflicts of interest in this work.