title: Synergistic enhancement of testosterone transdermal delivery.
abstract: In this study, the effects of occlusion, octisalate (OS), and propylene glycol (PG) on the in vitro skin permeability of testosterone (TES) have been investigated. TES (either alone or with OS 5% w/v) was applied as a finite dose to full-thickness neonatal porcine skin mounted in flow-through diffusion cells and the amount of TES appearing in the receptor solution (20% v/v ethanol) was determined over 24 h. The skin was occluded with a microscope glass cover slip and to determine the effect of PG, 400 microl of PG/water mixtures (of varying PG concentration) was applied. In addition, the effect of Solugel (a proprietary hydrogel containing PG 25% w/w) and Tegaderm (a semipermeable film dressing) on the permeation of TES was assessed. Occlusion had no effect on the permeation of TES, however, OS increased the flux of TES 2.9-fold. The concentration of PG which produced optimal TES flux was 20% v/v, and this concentration resulted in a 1.9-fold increase in TES permeation. By combining OS, PG, and occlusion, TES permeation was increased 8.7-fold, which was a synergistic enhancement. In addition, Solugel and Tegaderm, when applied to the skin, produced a similar enhancement in TES permeation to that produced by PG 25% w/w and occlusion.
authors.affiliation: Department of Pharmaceutics, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Nicolazzo
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Morgan
authors.forename: Barry L
authors.initials: BL
authors.lastname: Reed
authors.forename: Barrie C
authors.initials: BC
authors.lastname: Finnin
mesh_terms: D000279:Administration, Cutaneous; D000465:Algorithms; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D005079:Excipients; D066298:In Vitro Techniques; D011409:Propylene Glycols / Q000737:chemistry; D012869:Skin Absorption; D012995:Solubility; D013552:Swine; D013739:Testosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D005079:Excipients; D011409:Propylene Glycols; D013739:Testosterone