Zhao K, Singh J
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA.
J Pharm Sci. 2000 Jun;89(6):771-80. doi: 10.1002/(SICI)1520-6017(200006)89:6<771::AID-JPS9>3.0.CO;2-Y.
The effects of enhancers (5% terpenes; i.e., eugenol, limonene, and menthone) in combination with 50% propylene glycol in water (50% PG) on the in vitro percutaneous absorption of tamoxifen through the porcine epidermis, on biophysical changes in the stratum corneum (SC) lipids, on macroscopic barrier properties, and on binding of the drug to the SC were investigated. These enhancers in combination with 50% PG significantly increased (p<0.05) the permeability coefficient of tamoxifen in comparison with that of the control (50% PG in water). Fourier transform infrared spectroscopy (FT-IR) was employed to investigate the biophysical changes in the SC lipids. The FT-IR results showed that treatment of the SC with 5% terpenes/50% PG did not shift the asymmetric and symmetric C-H stretching absorbances peak positions to higher wavenumbers but resulted in a decrease in the peak heights and areas in comparison with the untreated SC. Treatment with menthone and limonene in combination with 50% PG significantly increased (p<0.05) the partition coefficient of tamoxifen in comparison with treatment with 50% PG alone. Also, exposure of the SC to 5% terpenes in combination with 50% PG significantly increased (p < 0.05) the in vitro transepidermal water loss (TEWL) in comparison with 50% PG alone. Thus, an enhancement by menthone, eugenol, and limonene in the permeability of the SC to tamoxifen is due to lipid extraction and macroscopic barrier perturbation. Moreover, the effective diffusion coefficient of tamoxifen through the epidermis was enhanced following the treatment with either 5% eugenol/50%PG or 5% limonene/50%PG compared with 50%PG alone.
研究了增强剂（5%萜烯，即丁香酚、柠檬烯和薄荷酮）与50%丙二醇水溶液（50%PG）组合对他莫昔芬经猪表皮的体外经皮吸收、角质层（SC）脂质的生物物理变化、宏观屏障特性以及药物与SC结合的影响。与对照组（50%丙二醇水溶液）相比，这些增强剂与50%PG组合显著提高（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SC脂质的生物物理变化。FT-IR结果表明，用5%萜烯/50%PG处理SC并未使不对称和对称C-H伸缩吸收峰位置向更高波数移动，但与未处理的SC相比，导致峰高和峰面积减小。与单独用50%PG处理相比，用薄荷酮和柠檬烯与50%PG组合处理显著提高（p<0.05）了他莫昔芬的分配系数。此外，与单独用50%PG相比，将SC暴露于5%萜烯与50%PG组合中显著提高（p<0.05）了体外经皮水分流失（TEWL）。因此，薄荷酮、丁香酚和柠檬烯对SC对他莫昔芬渗透性的增强作用是由于脂质提取和宏观屏障扰动。此外，与单独用50%PG相比，用5%丁香酚/50%PG或5%柠檬烯/50%PG处理后，他莫昔芬通过表皮的有效扩散系数得到增强。
