Skin Penetration-Enhancing Effect and Its Mechanism of Lactic Acid -Ethanol-Isopropyl Miristate System

Abstract

Permeation of ketotifen fumarate (KF), a model drug, through hairless rat full-thickness and stripped skins and two synthetic membranes (silicone membrane and polypropylene microporousm embrane) from lactic acid-ethanol-isopropyl myristate (IPM) system (LEI) and its related solvent systems was measured and compared to elucidate skin penetration-enhancing effect and its mechanism of the LEI system. Lactic acid and ethanol in the LEI system had an effect to increase permeability coefficient of KF through full-thickness skin. Those compounds increased KF flux through stripped skin, while they did not change permeability coefficient, which suggested that enhancing effect by LEI system may be realted to an increase of KF concentration in skin, especially in viable epdermis and dermis. Further experiments to measure skin permeation of two components in the LEI system, ethanol and lactic acid, and KF permeation experments using two synthetic membranes, models for lipid and pore pathway of stratum corneum, indicated that ethanol increased skin permeation of KF by increasing the drug concentration in skin and lactic acid increased KF solubility in skin containing ethanol, and that ethanol had an effect both on the pore and lipid pathway and lactic acid on pore pathway.