Zhao K, Singh J
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.
J Control Release. 1999 Dec 6;62(3):359-66. doi: 10.1016/s0168-3659(99)00171-6.
The purpose of this study was to investigate the mechanism(s) of percutaneous absorption enhancement of propranolol hydrochloride (PHCL) across porcine epidermis by terpenes (e.g. menthone and limonene) in combination with ethanol. The in vitro percutaneous absorption experiments were performed using Franz diffusion cells. The solubility of PHCL in control and enhancer solutions was determined through high-performance liquid chromatography. Partitioning of PHCL to powdered SC from control or enhancer solutions was also determined in order to investigate the binding of PHCL to the SC from the SC/enhancer system. Fourier transform infrared spectroscopy (FT-IR) was employed to study the biophysical changes in stratum corneum (SC) lipids. The in vitro macroscopic barrier properties were investigated by measuring transepidermal water loss (TEWL) using Tewameter. Five percent menthone or limonene in combination with ethanol (EtOH) (menthone/EtOH or limonene/EtOH) significantly increased (P<0.05) the flux of PHCL through porcine epidermis in comparison to the control (EtOH). The partitioning of PHCL to the SC from the SC/enhancer system was also significantly greater than the SC/control system. The above enhancers showed a decrease in the peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with the untreated SC, indicating the SC lipids extraction. Menthone/EtOH and limonene/EtOH enhanced (P<0.05) the in vitro TEWL through the epidermis in comparison to the control. Thus, an enhancement in the flux of PHCL by menthone/EtOH and limonene/EtOH is due to SC lipid extraction, macroscopic barrier perturbation, and improvement in the partitioning of the drug to the SC.
本研究的目的是探究萜类化合物（如薄荷酮和柠檬烯）与乙醇联合使用时，盐酸普萘洛尔（PHCL）经皮吸收增强的机制。使用Franz扩散池进行体外经皮吸收实验。通过高效液相色谱法测定PHCL在对照溶液和增强剂溶液中的溶解度。还测定了PHCL从对照溶液或增强剂溶液到角质层粉末的分配情况，以研究PHCL从角质层/增强剂系统与角质层的结合。采用傅里叶变换红外光谱（FT-IR）研究角质层（SC）脂质的生物物理变化。使用透皮水分流失仪（Tewameter）测量经表皮水分流失（TEWL），以研究体外宏观屏障特性。与对照组（乙醇）相比，5%的薄荷酮或柠檬烯与乙醇（薄荷酮/乙醇或柠檬烯/乙醇）联合使用显著增加（P<0.05）了PHCL通过猪表皮的通量。PHCL从角质层/增强剂系统到角质层粉末的分配也显著大于角质层/对照系统。与未处理的角质层相比，上述增强剂显示不对称和对称C-H伸缩吸收峰的高度和面积均降低，表明角质层脂质被提取。与对照组相比，薄荷酮/乙醇和柠檬烯/乙醇增强了（P<0.05）体外经表皮水分流失。因此，薄荷酮/乙醇和柠檬烯/乙醇对PHCL通量的增强作用是由于角质层脂质提取、宏观屏障扰动以及药物向角质层分配的改善。
