Zhao K, Singh J
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
J Control Release. 1998 Nov 13;55(2-3):253-60. doi: 10.1016/s0168-3659(98)00053-4.
The effect of chemical penetration enhancers (e.g., eugenol, d-limonene and menthone in combination with 50% ethanol) on the in vitro percutaneous absorption of tamoxifen through porcine epidermis has been investigated. The above enhancers significantly increased (p<0.05) the permeability coefficient of tamoxifen in comparison with the control (50% ethanol). Fourier transform infrared spectroscopy (FT-IR) was employed to investigate the biophysical changes in the stratum corneum (SC) lipids by the enhancer(s). FT-IR results showed that the treatment of the SC with enhancers did not produce a blue shift in the asymmetric and symmetric C-H stretching peak positions. However, all of the above enhancers showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with the untreated SC. A decrease in peak heights and areas is a measure of lipid extraction. Partitioning of tamoxifen to powdered SC from control and enhancer solutions was also determined. FT-IR and partitioning studies reveal that the enhancement in the permeability coefficient of tamoxifen by eugenol and d-limonene is due to lipid extraction and improvement in the partitioning of the drug to the SC. However, menthone enhanced the permeability of tamoxifen by increasing extraction of the SC lipids and not by improving the partitioning of the drug to the SC.
研究了化学渗透促进剂（如丁香酚、d-柠檬烯和薄荷酮与50%乙醇联用）对他莫昔芬经猪表皮体外透皮吸收的影响。与对照组（50%乙醇）相比，上述促进剂显著提高（p<0.05）了他莫昔芬的渗透系数。采用傅里叶变换红外光谱（FT-IR）研究促进剂对角质层（SC）脂质的生物物理变化。FT-IR结果表明，用促进剂处理SC后，不对称和对称C-H伸缩峰位置未产生蓝移。然而，与未处理的SC相比，上述所有促进剂的不对称和对称C-H伸缩吸收峰高度和面积均降低。峰高度和面积的降低是脂质提取的一种度量。还测定了他莫昔芬从对照溶液和促进剂溶液向粉末状SC的分配情况。FT-IR和分配研究表明，丁香酚和d-柠檬烯提高他莫昔芬渗透系数的原因是脂质提取以及药物向SC分配的改善。然而，薄荷酮通过增加SC脂质的提取而不是通过改善药物向SC的分配来提高他莫昔芬的渗透性。
