Biol. Pharm. Bull., 22(4),407-411, April 1999

Enhancement of Propylene Glycol Distribution in the Skin by High Purity cis-Unsaturated Fatty Acids with Different Alkyl Chain Lengths Having Different Double Bond Position

Kenji TAGUCHI,^{*, a} Shoji FUKUSHIMA,^a Yumiko YAMAOKA,^a Yoshikazu TAKEUCHI,^a and Masao SUZUKI^b

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University,^a Arise 518, Igawadani-cho, Nishi-ku, Kobe 651-2180, Japan, and Oleochemical Research Laboratory, NOF Corporation,^b 1-56, Oohama-cho, Amagasaki-shi, 660-0095, Japan.

Enhancement of skin distribution of propylene glycol (PG) in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths was studied in the rat using Fourier transform/attenuated total reflection (FT-IR/ATR) analysis. Two fatty acids with the double bond at the D9 position, palmitoleic acid (w7, D9) and oleic acid (w9, D9), enhanced PG flux into the dermis and increased the dermal steady state level of PG. In contrast, myristoleic acid (w5, D9) was extremely weak in its action. A positional effect of the w chain was observed. The rate of skin structural alteration increased in proportion to wchain length. The application of three fatty acids with the double bond at the w9 position, oleic acid (w9, D9) , gondoic acid (w9, D11), erucic acid (w9, D13) enhanced PG distribution in the skin. While, nervonic acid ( w9, D15) did not increase PG distribution in the skin. The relationship of the D/ w ratio to parameters characterizing the action of enhancers (PG_{peak area max}, T _{max alteration}, and the slope) suggest that skin distribution increases as the position of the double bond is shifted toward the hydrophilic end. It is therefore likely that the ratio of the D/ wchain length of the cis-unsaturated fatty acid determines the efficacy of these compounds as skin penetration enhancers. An adequate molecular volume may be required for cis-unsaturated fatty acids to act as enhancers.

Key words high purity cis-unsaturated fatty acid; alkyl chain length; skin penetration enhancer; Fourier transform/attenuated total reflection spectroscop.