Scientific article
English

Formulation and Evaluation of a Testosterone Transdermal Spray

Published inJournal of Pharmaceutical Sciences, vol. 95, no. 8, p. 1693-1702
Publication date2006-08
Abstract

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 µg/cm2 · 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.

Keywords
  • Aerosols
  • Transdermal drug delivery
  • Skin
  • Formulation
  • Passive diffusion
  • Transport
Citation (ISO format)
LEICHTNAM, Marie-Laure et al. Formulation and Evaluation of a Testosterone Transdermal Spray. In: Journal of Pharmaceutical Sciences, 2006, vol. 95, n° 8, p. 1693–1702. doi: 10.1002/jps.20641
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Article (Published version)
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Identifiers
Journal ISSN0022-3549
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