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 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).
Zhao
Hong
H
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
Choi
Min-Koo
MK
Kim
Jung Sun
JS
Yong
Chul-Soon
CS
Choi
Han-Gon
HG
Chung
Suk-Jae
SJ
Shim
Chang-Koo
CK
Kim
Dae-Duk
DD
D000279:Administration, Cutaneous; D000588:Amines / Q000008:administration & dosage*; D000818:Animals; D003671:DEET / Q000008:administration & dosage*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D007302:Insect Repellents / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects*; D013739:Testosterone / Q000097:blood*
D000588:Amines; D007302:Insect Repellents; D003671:DEET; D013739:Testosterone; C003935:dodecylamine