Suitability of Synthetic Copolymer Membranes as a Human Skin Alternative for In Vitro Skin Permeation Testing

Ryotaro Miki1, Soichiro Kimura1, Hideo Ueda1, Takeshi Shimamura1, Sachihiko Numajiri1, Toshinobu Seki1, Kazuhiko Juni1, Hiromi Kitano3 and Yasunori Morimoto1, 2

1Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan
2Research Institute of TTS Technology, Saitama, Japan
3Department of Applied Chemistry, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan

AATEX 15(1):14-27, 2010

Polydimethyl siloxane (PDMS) membrane has been widely used to evaluate the permeation of drugs, instead of human or animal skin, in screening for drug candidates for new transdermal drug delivery systems. However, PDMS membrane is not suitable for predicting the permeation of hydrophilic drugs, although human skin is permeable to hydrophilic drugs like mannitol. Thus, we aimed to prepare novel copolymer membranes which could be used for prediction of the skin permeability of hydrophilic drugs.
We synthesized the copolymers by a radical polymerization technique using methyl methacrylate, glycidyl methacrylate and macro-azoinitiator with a polyoxyethylene chain for mimicking drug permeation behavior through human skin. Gel permeation chromatography, 1H-NMR, X-ray diffraction and thermal analysis were conducted to characterize the synthesized copolymers. Results suggested that artificial membranes changed the balance of hydrophilic and lipophilic properties depending on the copolymer composition. In vitro permeation studies of 9 model compounds having different lipophilicities were performed using the artificial membranes and excised human skin. The results suggest that the synthetic copolymer membranes can be useful as an alternative to predict human skin permeability of not only lipophilic drugs but also hydrophilic drugs during the development of transdermal drug delivery systems.

key words: skin permeability, skin alternative, transdermal drug delivery system, copolymer membrane, artificial skin


(AATEX: Altern. Animal Test. EXperiment.: Alternatives to Animal Testing and EXperimentation)