Identification of penetration enhancers for testosterone transdermal delivery from spray formulations.
The goal of this study was to identify a suitable penetration enhancer-containing formulation for the transdermal delivery of testosterone from a spray. The first step involved in vitro measurement of drug flux from a 1:1 ethanol/water saturated solution across hairless rat skin, which had been pre-treated with a series of penetration enhancers. Isopropyl myristate (IPM) was found to be the most efficient excipient, increasing testosterone transport by more than a factor of 5. The enhancing ability of IPM was also apparent when the drug was formulated in 3:1 ethanol/propylene glycol, a more compatible vehicle for use in a spray. IPM was then incorporated into this formulation directly (as opposed to being used to pre-treat the skin) over a range of concentrations from 10-25% v/v, and testosterone transport was evaluated when delivered from either a solution, or from a mechanical spray, or from an aerosol (which also contained 50% v/v propellant). At the highest level of enhancer, the flux was improved 2.5-fold from both the spray and the aerosol, relative to a control. However, these formulations were far from optimally conceived, in that the amount of drug which eventually contacted the skin represented only approximately 10% of the pulverized quantity from the spray, and approximately 40% of that from the aerosol. Repeated application, especially from the aerosol, improved matters somewhat, but further work is clearly required before the concept can be developed for practical application.
Leichtnam
Marie-Laure
ML
School of Pharmaceutical Sciences, University of Geneva, 30 quai E. Ansermet, CH-1211 Geneva 4, Switzerland.
Rolland
Hervé
H
Wüthrich
Patrick
P
Guy
Richard H
RH