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.
Department of Pharmaceutics and Biopharmacertics, Showa Pharmaceutical University, Machida, Tokyo, Japan. fujii@ac.shoyaku.ac.jp
Makiko
M
Fujii
Yasuhiro
Y
Takeda
Minako
M
Yoshida
Mitsuo
M
Matsumoto
Yoshiteru
Y
Watanabe
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