Enhancement effect of p-menthane-3,8-diol on in vitro permeation of antipyrine and indomethacin through Yucatan micropig skin.
The enhancing effect of p-Menthane-3,8-diol (MDO) on skin permeation of antipyrine (ANP) and indomethacin (IM) through Yucatan micropig skin in vitro was compared with 1-menthol. p-Menthane-3,8-diol is a metabolite of 1-menthol and has little odor. It is easy to combine the vehicle because of lower lipophilicity than 1-menthol. All formulations contained 40% (v/v) ethanol. The permeation of ANP increased with MDO about three times that without enhancer by increasing ANP concentration in the skin. However, the MDO effect was about a quarter that of 1-menthol. The permeation of IM with MDO was about 15 times that with no enhancer and it was almost the same as that with 1-menthol. The lag time of permeation was not significantly changed by MDO, which was not so in the case of 1-menthol. Skin concentration of IM increased about 11 times and six times with MDO and 1-menthol, respectively. MDO and 1-menthol partitioned to the skin relatively high concentrations, 5.9 and 2.5 mg/ cm3, respectively. The solubility of IM in the skin was improved by MDO, and consequently, the permeation of IM was enhanced.
Fujii
Makiko
M
Department of Pharmaceutics and Biopharmacertics, Showa Pharmaceutical University, Machida, Tokyo, Japan. fujii@ac.shoyaku.ac.jp
Takeda
Yasuhiro
Y
Yoshida
Minako
M
Matsumoto
Mitsuo
M
Watanabe
Yoshiteru
Y
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000983:Antipyrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D000081005:Cyclohexane Monoterpenes; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008610:Menthol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010539:Permeability; D012869:Skin Absorption; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D000277:Adjuvants, Pharmaceutic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000081005:Cyclohexane Monoterpenes; D008610:Menthol; C005804:terpin; D000983:Antipyrine; D007213:Indomethacin