TY - JOUR
T1 - Testosterone skin permeation enhancement by menthol through formation of eutectic with drug and interaction with skin lipids
AU - Kaplun-Frischoff, Yael
AU - Touitou, Elka
PY - 1997/12
Y1 - 1997/12
N2 - The aim of this investigation was to elucidate the mechanism of skin permeation enhancement of the lipophilic drug testosterone, by menthol. Menthol was found to form eutectic mixtures with testosterone, cholesteryl oleate, and ceramides. DSC measurements showed that menthol drastically lowers the T(m) of testosterone, from 153.7 to.39.9 °C. The decrease in T(m) resulted in an increase in the solubility of testosterone in an aqueous ethanol vehicle by 2.8-fold, which caused a corresponding 2.8-fold increase in the flux of testosterone. A further increase in skin flux, to eight times the base line, could be attributed to the effect of menthol on the skin barrier properties. This assumption is supported by DSC results showing that menthol decreases the T(m), of cholesteryl oleate and ceramides and modifies the thermogram profile of isolated stratum corneum. The results of this investigation indicate that menthol affects skin permeation by a dual mechanism: by forming a eutectic with the penetrating compound, thereby increasing its solubility, and by altering the barrier properties of the stratum corneum. Moreover, this study indicates that both types of interactions must be taken into consideration when using chemical enhancers and that decreasing the melting temperature of the permeant through formation of a eutectic could be one approach for increasing solubility and permeation rates.
AB - The aim of this investigation was to elucidate the mechanism of skin permeation enhancement of the lipophilic drug testosterone, by menthol. Menthol was found to form eutectic mixtures with testosterone, cholesteryl oleate, and ceramides. DSC measurements showed that menthol drastically lowers the T(m) of testosterone, from 153.7 to.39.9 °C. The decrease in T(m) resulted in an increase in the solubility of testosterone in an aqueous ethanol vehicle by 2.8-fold, which caused a corresponding 2.8-fold increase in the flux of testosterone. A further increase in skin flux, to eight times the base line, could be attributed to the effect of menthol on the skin barrier properties. This assumption is supported by DSC results showing that menthol decreases the T(m), of cholesteryl oleate and ceramides and modifies the thermogram profile of isolated stratum corneum. The results of this investigation indicate that menthol affects skin permeation by a dual mechanism: by forming a eutectic with the penetrating compound, thereby increasing its solubility, and by altering the barrier properties of the stratum corneum. Moreover, this study indicates that both types of interactions must be taken into consideration when using chemical enhancers and that decreasing the melting temperature of the permeant through formation of a eutectic could be one approach for increasing solubility and permeation rates.
UR - http://www.scopus.com/inward/record.url?scp=0031445928&partnerID=8YFLogxK
U2 - 10.1021/js9701465
DO - 10.1021/js9701465
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C2 - 9423153
AN - SCOPUS:0031445928
SN - 0022-3549
VL - 86
SP - 1394
EP - 1399
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 12
ER -