Synergistic enhancement of testosterone transdermal delivery.
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.
Nicolazzo
Joseph A
JA
Department of Pharmaceutics, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Morgan
Timothy M
TM
Reed
Barry L
BL
Finnin
Barrie C
BC
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*
D005079:Excipients; D011409:Propylene Glycols; D013739:Testosterone