Enhanced bioavailability of lacidipine via microemulsion based transdermal gels: Formulation optimization, ex vivo and in vivo characterization

The purpose of the present study was to develop and optimize the microemulsion based transdermal therapeutic system for lacidipine (LCDP), a poorly water soluble and low bioavailable drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of isopropyl myristate, Tween 80 and Labrasol. The microemulsion was optimized using a three-factor, three-level Box-Behnken design, the independent variables selected were isopropyl myristate, surfactant mixture (Tween 80 and Labrasol) and water; dependent variables (responses) were cumulative amount permeated across rat abdominal skin in 24 h (Q(24): Y-1), flux (Y-2), and lag time (Y-3). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y-1, Y-2 and Y-3. The statistical validity of the polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with 10 confirmatory runs indicated high degree of prognostic ability of response surface methodology. The gel of optimized formulation (ME-OPT) showed a flux of 43.7 mu g cm(-2) h(-1), which could meet the target flux (112.16 mu g cm(-2) h(-1)). The bioavailability studies in rabbits showed that about 3.5 times statistically significant (p<0.05) improvement in bioavailability, after transdermal administration of microemulsion gel compared to oral suspension. The ex vivo-in vivo correlation was found to have biphasic pattern and followed type A correlation. Microemulsion based transdermal therapeutic system of LCDP was developed and optimized using Box-Behnken statistical design and could provide an effective treatment in the management of hypertension. (C) 2010 Elsevier B.V. All rights reserved.