LAUSR

PURPOSE Penetration enhancers are necessary to overcome a formidable barrier function of the stratum corneum in the development of topical formulations. Recently, non-lamella liquid crystal (NLLC)-forming lipids such as glycerol monooleate and phytantriol (PHY) are gaining increasing attention as a novel skin permeation enhancer. In the present study, fluorescein sodium (FL-Na) was used as a model hydrophilic drug, and acryl-base pressure-sensitive adhesive (PSA) tape containing NLLC forming lipids, mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE) or PHY, was prepared to enhance drug permeation through the skin. METHODS A PSA patch containing FL-Na was prepared by mixing FL-Na entrapped in NLLC and acrylic polymer. FL permeation through excised hairless rat skin, and also human skin, was investigated. Changes in lipid structure, folding/unfolding state of keratin in the stratum corneum, and penetration of MGE into the stratum corneum were investigated using confocal Raman microscopy. RESULTS Enhanced FL permeation was observed by the application of a PSA patch containing MGE and PHY. Especially, dramatically enhancement effect was confirmed by 15% of MGE contained formulation. Penetration of MGE provided diminished orthorhombic crystal structure and a peak shift of the aliphatic CH3 vibration of keratin chains toward lower wavenumbers. CONCLUSION The present results suggested that the formulation development by adding MGE may be useful for improving the skin permeation of mal-permeable drugs such as hydrophilic drugs.