Development of a transdermal patch of methadone: in vitro evaluation across hairless mouse and human cadaver skin.
A 3-day monolithic polyacrylate adhesive dispersion type delivery system containing methadone was fabricated and in vitro permeation through hairless mouse and human cadaver skins was conducted. The effect of skin permeation enhancers was also investigated. Skin permeation rate across human cadaver skin was found to be lower than that of hairless mouse. Skin permeation profiles across both types of skins showed a membrane permeation controlled cumulative amount permeated (Q) versus time (t) relationship. Skin permeation rate was found to be dependent on both adhesive film thickness and loading dose of the drug in the matrix. Effective skin permeation rate across the hairless mouse skin was obtained from a patch with 1.5 mm thickness and 15% w/w loading dose. n-Decylmethyl sulfoxide and Azone were found to produce an effective skin permeation rate of methadone through human cadaver skin at a 5% w/w concentration. These initial studies demonstrated the feasibility of methadone administration through intact skin from a transdermal patch.
Ghosh
T K
TK
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Howard University, Washington, DC 20059, USA.
Bagherian
A
A
D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives; D005079:Excipients; D006801:Humans; D066298:In Vitro Techniques; D008691:Methadone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D009294:Narcotics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012869:Skin Absorption
D001381:Azepines; D005079:Excipients; D009294:Narcotics; C035229:laurocapram; C054274:1-decyl methyl sulfoxide; D008691:Methadone; D004121:Dimethyl Sulfoxide