Effect of triethanolamine as counter ion on the transdermal permeation of candesartan

Abstract

The aim of this work was to develop a transdermal gel formulation for enhanced delivery of candesartan. The in vitro skin permeation of the drug was examined using modified Franz type diffusion cells and epidermal membrane, taken from full thickness hairless mouse skin. Initially, a full 24 factorial design was employed, in order to estimate the effects and interactions of the following factors: the chemical form of the Active Pharmaceutical Ingredient (API), the concentration of triethanolamine (TEtA), the concentration of 1,8-cineole and the type of the vehicle's co-solvent, on the in vitro skin permeation. The experimental design revealed the optimum formulation consisting of candesartan, 5% TEtA, 10% 1,8-cineole and glycerol formal, which provided an increased flux, approximately two hundred times higher than the control formulation. Furthermore, NMR and mass spectrometry demonstrated the ion pair formation between TEtA and candesartan as an effective strategy for significantly improving its in vitro skin permeation.