In vitro evaluations of transdermal levonorgestrel

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Dermatology

Background:

• Transdermal drug delivery offers a non-invasive route for systemic administration.
• Contraceptive agents like levonorgestrel require effective delivery systems for sustained release.
• Penetration enhancers are crucial for improving drug permeation through the skin barrier.

Purpose of the Study:

• To develop and evaluate transdermal delivery systems for co-delivering levonorgestrel and ethyl acetate.
• To assess the delivery performance across various animal skin models (hairless guinea pig, hairless mouse, rat).
• To investigate the influence of membrane composition and drug formulation on delivery kinetics.

Main Methods:

• Fabrication of transdermal devices using ethylene vinyl acetate (EVAc) copolymers and blends with poly(methacrylates).
• Formulation of reservoir phase with levonorgestrel-saturated ethyl acetate gelled with hydroxypropyl cellulose.
• Evaluation of drug and enhancer delivery rates using in vitro permeation studies across different animal skins.

Main Results:

• All tested devices demonstrated co-delivery of levonorgestrel and ethyl acetate at comparable rates across all skin types.
• Levonorgestrel flux closely followed ethyl acetate flux until enhancer depletion.
• Sustained levonorgestrel delivery was observed even after the depletion of ethyl acetate from the devices.

Conclusions:

• Transdermal systems effectively co-deliver levonorgestrel and ethyl acetate, showing consistent performance across different skin models.
• The release kinetics are primarily governed by the penetration enhancer's flux, ensuring sustained drug delivery.
• These findings support the potential of such systems for effective transdermal contraceptive delivery.