The purpose of the present investigation was to evaluate 6-O-palmitoyl ascorbic acid (ASC16) and 6-O-lauril ascorbic acid (ASC12) for their capacity to promote permeation of Ibuprofen (IBU) through hairless mouse skin in vitro. The permeation of Arfen® (IBU 10% P/P, commercial product), IBU solution (0.85% P/P, pH 7.4, 66.7 mM phosphate buffer: Isopropyl alcohol; 80:20) and IBU (0.85% P/P) vehiculized in ASCn coagels (5% w/v) were measured and comparatively analyzed. Although IBU release from the formulation was faster in the case of Arfen® in comparison to ASCn coagel, the permeation of IBU was significantly increased when the drug was vehiculized in these systems, being ASC12 the most effective as enhancer. This result demonstrated the potential usefulness of the lamellar liquid crystalline system obtained from ASCn auto-aggregation for topical administration of drugs.