Synergic enhancing-effect of DEET and dodecylamine on the skin permeation of testosterone from a matrix-type transdermal delivery system

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 μg/cm²/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 cm² is applied, the human cadaver skin permeation rate of 5.74 μg/cm²/h achieved in this study can be interpreted as being equivalent to delivering ～ 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 cm².