Formulation and evaluation of a testosterone transdermal spray.
The long-term goal is to develop a spray formulation for transdermal testosterone delivery, and to optimize the drug's skin permeability. Testosterone transport from a series of ethanol/propylene glycol (PG)/water formulations was assessed in vitro across hairless rat skin, and the optimal composition determined. The formulation was then modified for delivery from a mechanical spray, and from an aerosol containing a high percentage of propellant. Drug transport was greatest from a saturated solution in 1:1:1 ethanol/PG/water (1.7 +/- 0.2 microg/cm(2) . h); five spray formulations were then tested, but only 1:1 ethanol/PG achieved a comparable flux. Increasing the % ethanol in the mixture increased evaporation rate but did not alter testosterone delivery. Formulation as an aerosol produced primarily unstable vehicles (phase separation, crystallization). Only 3:1 ethanol/PG remained stable, but no significant improvement in drug transport was observed (testosterone precipitated rapidly at the skin surface). The 1:1:1 ethanol/PG/water saturated solution suggested that some penetration enhancement was possible. Eliminating water to improve sprayability identified 1:1 ethanol/PG as a vehicle, which might allow transient supersaturation (and improved delivery). However, this effect was not improved by using a pressurized aerosol due to instability. Finally, testosterone fluxes were 5 to 10-fold lower than those required for useful transdermal therapy.
Leichtnam
Marie-Laure
ML
School of Pharmaceutical Sciences, University of Geneva, quai E. Ansermet, Switzerland.
Rolland
Hervé
H
Wüthrich
Patrick
P
Guy
Richard H
RH
D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*
D013739:Testosterone