Formulation and evaluation of a testosterone transdermal spray.

Area of Science:

• Dermatology and Pharmaceutical Sciences
• Drug Delivery Systems
• Transdermal Drug Delivery

Background:

• Transdermal drug delivery offers a non-invasive route for systemic medication administration.
• Optimizing testosterone's skin permeability is crucial for developing effective transdermal formulations.
• Ethanol/propylene glycol/water mixtures are commonly explored for enhancing drug penetration.

Purpose of the Study:

• To develop and optimize a sprayable formulation for transdermal testosterone delivery.
• To assess and enhance testosterone's skin permeability using various solvent systems.
• To evaluate the stability and efficacy of spray and aerosol formulations for testosterone transport.

Main Methods:

• In vitro assessment of testosterone transport across hairless rat skin using ethanol/propylene glycol/water formulations.
• Modification of optimal formulations for mechanical spray and aerosol delivery systems.
• Analysis of drug flux, evaporation rates, and formulation stability (phase separation, crystallization).

Main Results:

• Highest testosterone transport (1.7 +/- 0.2 microg/cm(2).h) was achieved with a saturated solution in 1:1:1 ethanol/PG/water.
• Spray formulations, including 1:1 ethanol/PG, showed comparable or lower drug flux; aerosol formulations exhibited instability.
• Testosterone fluxes were significantly lower (5-10 fold) than required for effective transdermal therapy.

Conclusions:

• While some penetration enhancement was observed with ethanol/PG/water, achieving therapeutically relevant transdermal testosterone delivery via spray or aerosol remains a significant challenge.
• Formulation instability in aerosols and limited permeability in sprayable systems hinder effective testosterone transport.
• Further research is needed to overcome the low skin permeability and formulation stability issues for successful transdermal testosterone therapy.