In vitro percutaneous absorption enhancement of a lipophilic drug tamoxifen by terpenes.
Tamoxifen is a highly lipophilic drug that is widely used in breast malignancies and also as a prophylactic therapy in women at high risk for the development of this disease. Recently, the terpenes have been reported to show an enhancement effect on percutaneous drug absorption. The effect of terpenes (e.g. carvone, 1,8-cineole, menthol, and thymol) was studied on the in vitro percutaneous absorption of tamoxifen through porcine epidermis. The above terpenes (5% w/v) in combination with 50% ethanol significantly (P < 0.01) increased the permeability coefficient of tamoxifen in comparison to the control (50% ethanol). The solubility of tamoxifen was determined in the control and enhancer solutions to correct the permeability enhancement by way of fractional solubility adjustment. Binding of tamoxifen to powdered stratum corneum from control and enhancer solutions was also determined. Binding studies reveal that the enhancement in the permeability coefficient of tamoxifen by menthol and thymol is due at least in part, to improvement in the partitioning of the drug to the stratum corneum. In conclusion, terpenes in combination with ethanol can be used to enhance the percutaneous absorption of the highly lipophilic drug tamoxifen.
Gao
S
S
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.
Singh
J
J
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism* / Q000493:pharmacokinetics; D000081005:Cyclohexane Monoterpenes; D003511:Cyclohexanols; D004817:Epidermis / Q000378:metabolism; D000077591:Eucalyptol; D005260:Female; D066298:In Vitro Techniques; D008610:Menthol / Q000031:analogs & derivatives / Q000494:pharmacology; D039821:Monoterpenes; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013552:Swine; D013629:Tamoxifen / Q000378:metabolism* / Q000493:pharmacokinetics; D013729:Terpenes / Q000494:pharmacology*; D013943:Thymol / Q000494:pharmacology
D000890:Anti-Infective Agents; D018931:Antineoplastic Agents, Hormonal; D000081005:Cyclohexane Monoterpenes; D003511:Cyclohexanols; D039821:Monoterpenes; D013729:Terpenes; D013629:Tamoxifen; D008610:Menthol; D013943:Thymol; C006923:carvone; D000077591:Eucalyptol