Permeation Enhancer in Microemulsions and Microemulsion-Based Gels: A Comparison of Diethylene Glycol Monoethyl Ether and Oleyl Alcohol.

Abstract

Microemulsions have been commonly used with various permeation enhancers to improve permeability through the skin. The purpose of this study was to compare the release and permeation ability of two commonly used permeation enhancers-diethylene glycol monoethyl ether (DGME) and oleyl alcohol-by the changes in oil composition, the addition of a gelling agent, and water content using ibuprofen as a model drug. Four microemulsions were formulated, selection was based on ternary phase diagrams, and physicochemical properties were evaluated. The release and permeation of the microemulsion formulations were performed in vitro by Franz cell studies on a regenerated cellulose membrane and a Strat-M^® membrane, respectively, and the amount of ibuprofen permeated and released was analyzed by high-performance liquid chromatography (HPLC). All four microemulsions were compatible with the skin pH, and the average pH ranged from 4.9 to 5.6. The average droplet size of the microemulsions ranged from 119.8 to 153.3 nm. Drug release was significantly the highest from the gel-based microemulsions (59% and 64%, p < 0.05). However, there was a fourfold difference in drug permeation from these gels-a significantly higher permeation from the microemulsion-gel containing oleic acid and oleyl alcohol compared to the DGME formulation. These results indicated that the microemulsion-gel with oleyl alcohol as the permeation enhancer could be a preferable formulation approach for the topical administration of ibuprofen. These results highlight the need for optimization of the microemulsion formulation to confirm the permeation-enhancing effects of chosen permeation enhancers despite being a well-known permeation enhancer.