Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne.

Abstract

The main objective of the study was to prepare the microemulsions containing adapalene (MEs-Ap) to enhance epidermal penetration, dermal retention, and local bioavailability compared with the commercial preparation. The optimal formulations were selected by solubility experiments, pseudo-ternary phase diagram, and percutaneous permeation experiments and the physiochemical properties were also investigated. Then, the study of permeability, retention, safety, pharmacodynamics, and pharmacokinetics in the skin for MEs-Ap compared with the commercial preparation were researched. The optimized formulation was developed as follows: the ratio of AP, isopropyl myristate, polyoxyethylene hydrogenated castor oil, ethanol, and water was 0.01:1:1.25:3.75:4 (w/w). The globule size and average viscosity of the optimized MEs-Ap were 99.34nm and 1.7mPa·s, respectively, which was oil-in-water microemulsion without serious irritation or allergy for skin. The Js, Qn, and Qretention of MEs-Ap (0.81 ± 0.19μg/cm2/h, 24.73 ± 4.24μg/cm2, 2.08 ± 0.18μg/cm2) were apparently higher than Differin® (0.022 ± 0.009μg/cm2/h, 0.536 ± 0.103μg/cm2, and 0.523 ± 0.130μg/cm2) respectively. The local bioavailability study showed that the AUC0 → 36h of the MEs-Ap in the dermal (19.6 ± 1.22μg/cm2) was significantly improved comparing to Differin® (13.9 ± 1.73μg/cm2) (p < 0.01). The pharmacodynamics study showed that the therapeutic effect of MEs-Ap was better than that of Differin® in the acne model of rabbit auricle. These results suggested that the MEs-Ap could be considered as a having higher epidermal penetrability, dermal retention, local bioavailability, efficacy, and safety topical preparations for acne. Graphical abstract.