Formulation Optimization of Estradiol Microemulsion Using Response Surface Methodology

The aim of the current study was to find an optimal estradiol-loaded microemulsion with higher permeation rate and shortened lag time (LT) for transdermal application by using a response surface methodology (RSM) and constrained mixture design. Isopropyl myristate (X₁), distilled water (X₂), and ethanol (X₃) were selected as independent variables, whereas the viscosity of microemulsion and permeation parameters including the cumulative amount at 24 h (Q_24h) and LT of estradiol-loaded microemulsion through skin were set as dependent variables. The result showedthat the three independent variables had a remarkable effect (p < 0.05) on the dependent variables. Moreover, the predicted and observed values of these three dependent variables of the optimal microemulsion formulations, which were produced by the RSM optimization technique, were close, demonstrating that RSM was a useful technique for optimizing pharmaceutical formulations. However, the experimental estradiol-loaded microemulsion with higher permeation rate was expected to provide effective therapeutic concentration in a workable administration area. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4383–4389, 2011