Untitled

Abstract

The objective of the study was to investigate the effect of microemulsion on in-vitro skin permeation, percutaneous absorption of Irbesartan and to postulate probable mechanism of skin permeation. Microemulsion was prepared by aqueous phase titration method. Pseudoternary phase diagrams were constructed for the microemulsions. Thermodynamic stability study was carried out on selected microemulsions. Characterization of selected Irbesartan-loaded microemulsions was done by droplet size and polydispersity index determination. Physicochemical properties of Irbesartan-loaded microemulsions were determined using reported procedures. In-vitro skin permeation was determined using Franz cell. Skin permeation mechanism was assessed by Fourier Transform Infra-Red spectra analysis, Differential Scanning Calorimetry and activation energy measurement. A non-compartmental pharmacokinetic study was carried out to estimate the percutaneous absorption through the rat skin. The particle size and polydispersity index of the spherically shaped microemulsions were in the range of 83-86 nm and 0.270-0.290 respectively. In-vitro skin permeation study gave the permeability coefficient and steady state flux of Irbesartan to be 3.52 (×10-3) cm/h and 17.59 ± 0.38 µg/cm 2 /h for oil-in-water (O/W); 6.63 (×10-3) cm/h and 33.16 ± 0.33 µg/cm 2 /h for water-in-oil (W/O) respectively. Compared with the Irbesartan suspensions, pharmacokinetics of Irbesartan-loaded microemulsions in Wistar rats indicated higher plasma drug concentrations and larger area under the curve. The pharmacokinetic and in-vitro studies suggest that microemulsion could be an effective transdermal drug delivery system to improve bioavailability of Irbesartan. Disruption of lipid bilayer, protein denaturation and skin hydration are considered to be the probable skin permeation mechanism.