The effects of pressure-sensitive adhesives and solubilizers on the skin permeation of testosterone from a matrix-type transdermal delivery system.
Matrix-type transdermal delivery systems of testosterone (TS) were formulated with three different pressure-sensitive adhesives (PSA). The effects of PSA, skin permeation enhancers, and solubilizers on the rat skin permeation rate of TS were systematically investigated. Without a solubilizer, the skin permeation rate of TS reached its maximum value when only 2% of TS was loaded in the matrix and the crystal formation in the matrix was very rapid and severe. Two surfactants differing in their hydrophile-lipophile balance (HLB) number were, therefore, considered. Span 80, which was of the lower HLB number, was more effective than Tween 80 in increasing the solubility, and thereby increasing the permeation rate of TS. Moreover, the concentrations of both the solubilizer and the skin permeation enhancer affected the skin permeation rate. Thus, the highest skin permeation rate (4.14 micrograms/cm2/hr) was achieved when 2% TS was loaded in DuroTak 87-2516 together with 10% Span 80 and 3% dodecylamine, the permeation enhancer. In vivo study showed that the application of an experimental patch on rat abdominal skin resulted in a prompt and significantly higher plasma concentration of TS than that of a commercial product (Testoderm) designed to apply on the scrotal skin. The area under the curve (AUC) increased linearly as the loading dose of TS increased up to 6%. Thus, based on these results, a non-scrotal matrix-type transdermal delivery system of TS could be developed.
Zhao
Hong
H
College of Pharmacy, Pusan National University, Pusan 609-735, South Korea.
Park
Dong-Woo
DW
Kim
Soo-Kyun
SK
Lee
Chi-Ho
CH
Kim
Dae-Duk
DD
D000269:Adhesives / Q000737:chemistry* / Q000494:pharmacology; D000279:Administration, Cutaneous; D000588:Amines / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006601:Hexoses / Q000494:pharmacology; D008297:Male; D011136:Polysorbates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects*; D013501:Surface-Active Agents / Q000494:pharmacology; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
D000269:Adhesives; D000588:Amines; D006601:Hexoses; D011136:Polysorbates; D013501:Surface-Active Agents; C018665:sorbitan monooleate; D013739:Testosterone; C003935:dodecylamine