Development of clove oil based nanoemulsion of olmesartan for transdermal delivery: Box-Behnken design optimization and pharmacokinetic evaluation

The aim of this study was to develop and optimize a transdermal nanoemulsion formulation of olmesartan using Box-Behnken design and to evaluate it for pharmacokinetic study. Box-Behnken experimental design was applied for optimization of olmesartan nanoemulsions. The independent variables were clove oil (X-1), S-mix (X-2) and water (X-3) while particle size (Y-1), polydispersity index (Y-2) and olmesartan transdermal flux (Y-3) were the dependent variables. Further the optimized formulation obtained was then tested in rats for an in vivo pharmacokinetic study. Results indicate that the developed nanoemulsion carrier of olmesartan provides reasonable particle size, polydispersity index and transdermal flux. The optimized formulation has presented the particle size of 53.11 +/- 3.13 nm, polydispersity index 0335 +/- 0.008 and transdermal flux 12.65 +/- 1.60 mu g/cm(2)/h. Confocal laser scanning microscopy revealed an enhanced penetration of Rhodamine B loaded nanoemulsion carriers to the deeper layers of the skin. Furthermore, in vivo pharmacokinetic study of optimized formulation showed a significant increase in the bioavailability (1.23 times) compared with oral formulation of olmesartan by virtue of better permeation through rat skin. The developed nanoemulsion formulation could be used as an antihypertensive dosage form for effective transdermal delivery of olmesartan. (C) 2015 Elsevier B.V. All rights reserved.