Goto S, Uchida T, Lee C K, Yasutake T, Zhang J B
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
J Pharm Sci. 1993 Sep;82(9):959-63. doi: 10.1002/jps.2600820918.
The effects of glycerides, short-chain alcohols, and their binary vehicles as donor components on the permeation of ketoprofen (KP) across the excised hairless mouse skin were evaluated with the modified LOVEDAY-type diffusion cell. Among single vehicles, Panasate 800 as tricaprylin appeared to be the most favorable lipophilic vehicle, with no toxicity and with a short lag time (0.9 h), and methanol (MeOH) or ethanol (EtOH) as hydrophilic single vehicles showed the highest KP permeation flux (244.1 and 134.1 micrograms/cm2/h, respectively). Furthermore, KP permeation was enhanced remarkably by the combination of EtOH and Panasate 800 compared with each single vehicle as reflected in the decreased lag time and increased flux. The greatest enhancement was observed in the EtOH/Panasate 800 (40/60) binary vehicle (permeation ratio at 24 h, 40.0%; steady-state flux, 314.0 micrograms/cm2/h; lag time, 3.7 h). Further investigations involving stripping studies and KP accumulation within the skin were performed to explain the mechanism of enhancement caused by the above binary vehicle. It was suggested that the mutual enhancement effect of EtOH/Panasate 800 (40/60) binary vehicle is due to decreasing the barrier ability of the stratum corneum by EtOH and the viable skin by Panasate 800.
采用改良的LOVEDAY型扩散池，评估甘油酯、短链醇及其二元载体作为供体成分对酮洛芬（KP）透过离体无毛小鼠皮肤的影响。在单一载体中，作为三辛酸甘油酯的Panasate 800似乎是最适宜的亲脂性载体，无毒且滞后时间短（0.9小时），而作为亲水性单一载体的甲醇（MeOH）或乙醇（EtOH）显示出最高的KP渗透通量（分别为244.1和134.1微克/平方厘米/小时）。此外，与每种单一载体相比，EtOH和Panasate 800的组合显著增强了KP的渗透，这体现在滞后时间缩短和通量增加上。在EtOH/Panasate 800（40/60）二元载体中观察到最大程度的增强（24小时的渗透比为40.0%；稳态通量为314.0微克/平方厘米/小时；滞后时间为3.7小时）。进行了涉及皮肤剥离研究和皮肤内KP蓄积的进一步研究，以解释上述二元载体引起增强作用的机制。结果表明，EtOH/Panasate 800（40/60）二元载体的相互增强作用是由于EtOH降低了角质层的屏障能力，而Panasate 800降低了活性皮肤的屏障能力。
