Zhao Hong, Choi Min-Koo, Kim Jung Sun, Yong Chul-Soon, Choi Han-Gon, Chung Suk-Jae, Shim Chang-Koo, Kim Dae-Duk
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
Drug Deliv. 2009 Jul;16(5):249-53. doi: 10.1080/10717540902896586.
The synergic in vitro skin permeation enhancing-effect of N,N-diethyl-m-toluamide (DEET) and dodecylamine was investigated in order to develop a novel non-scrotal matrix-type transdermal delivery system of testosterone (TS). When DEET was loaded in DuroTak 87-2510 together with 2% TS and 3% dodecylamine, the in vitro rat skin permeation rate of TS synergistically increased as DEET concentration increased up to 0.5%. No further increase in permeation was observed thereafter and a plateau was observed up to 3.8% DEET. Moreover, compared to 0.5% DEET concentration, the addition of 3.8% of DEET in combination with 3% dodecylamine and 6% TS further increased the permeation rate of TS, and the maximum permeation rate of 11.21 microg/cm(2)/h was achieved. The in vitro skin permeation rates of TS from a transdermal delivery system of DuroTak 87-2510 containing 6% TS, 3% dodecyamine, and 3.8% DEET were in the following order: hairless mouse skin > rat skin > human cadaver skin. Assuming that a system with a surface area of 60 cm(2) is applied, the human cadaver skin permeation rate of 5.74 microg/cm(2)/h achieved in this study can be interpreted as being equivalent to delivering approximately 8. 27 mg of TS per day. Considering that the commercially available product (Testoderm TTS) for non-scrotal skin of the same surface area is designed to administer 5 mg of TS per day, the new formulation could maintain therapeutic plasma concentration of TS at a smaller surface area of 40 cm(2).
为开发一种新型的非阴囊基质型睾酮(TS)透皮给药系统,研究了N,N - 二乙基间甲苯胺(避蚊胺,DEET)和十二胺的体外协同皮肤渗透增强作用。当将DEET与2%的TS和3%的十二胺一起载入DuroTak 87 - 2510中时,随着DEET浓度增加至0.5%,TS的体外大鼠皮肤渗透速率协同增加。此后未观察到渗透进一步增加,直至3.8%的DEET时观察到一个平台期。此外,与0.5%的DEET浓度相比,添加3.8%的DEET与3%的十二胺和6%的TS组合进一步提高了TS的渗透速率,并实现了11.21μg/cm²/h的最大渗透速率。含有6%的TS、3%的十二胺和3.8%的DEET的DuroTak 87 - 2510透皮给药系统中TS的体外皮肤渗透速率顺序如下:无毛小鼠皮肤>大鼠皮肤>人尸体皮肤。假设应用表面积为60cm²的系统,本研究中实现的人尸体皮肤渗透速率5.74μg/cm²/h可解释为每天输送约8.27mg的TS。考虑到相同表面积的非阴囊皮肤的市售产品(Testoderm TTS)设计为每天给药5mg的TS,新配方可在40cm²的较小表面积下维持TS的治疗血浆浓度。