Development, optimization and ex-vivo evaluation of a transdermal formulation containing trazodone

Area of Science:

• Pharmaceutical Sciences
• Dermatology
• Drug Delivery Systems

Background:

• Trazodone, a triazolpyridine derivative, is orally administered for depression.
• Transdermal delivery may mitigate side effects and improve adherence.
• Current research explores optimizing transdermal systems for trazodone.

Purpose of the Study:

• Evaluate pH and permeation enhancers on trazodone skin permeability ex-vivo.
• Develop and optimize a transdermal drug delivery system for trazodone hydrochloride.
• Assess the influence of vehicle pH, fatty acids, and patch formulation on drug permeation.

Main Methods:

• Ex-vivo permeation studies using porcine skin.
• Investigation of pH effects on trazodone solubility and partitioning.
• Formulation and testing of transdermal patches with varying drug loading and enhancers.
• Analysis of transdermal flux and enhancement factors.

Main Results:

• Vehicle pH complexly influences trazodone permeation.
• Fatty acids (oleic, lauric) significantly enhance permeation (approx. 100-fold enhancement factor).
• Optimal fatty acid concentration for permeation enhancement is 2-3%.
• Drug loading in patches is more critical than adhesive matrix components for permeation.
• Lauric acid enhancement in solution did not translate to patches.

Conclusions:

• Transdermal trazodone delivery is feasible, with fatty acids showing significant permeation enhancement.
• Patch formulation requires careful consideration of drug loading.
• While not clinically relevant for depression, transdermal trazodone may be suitable for insomnia and anxiety disorders at lower doses.