Transdermal agomelatine microemulsion gel: pyramidal screening, statistical optimization and in vivo bioavailability

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Dermatology

Background:

• Agomelatine exhibits poor oral bioavailability (<5%) due to extensive first-pass metabolism.
• Transdermal drug delivery offers an alternative route to bypass hepatic metabolism.
• Microemulsions are promising vehicles for enhancing drug solubility and skin permeation.

Purpose of the Study:

• To formulate and optimize a transdermal microemulsion gel of agomelatine.
• To enhance the transdermal bioavailability of agomelatine.
• To investigate the potential of microemulsion gel for improved antidepressant delivery.

Main Methods:

• Pyramidal screening and Design-Expert software for formulation optimization.
• Utilized Capryol 90 (oil), Cremophor RH40/Transcutol HP (surfactant/cosurfactant), and water.
• Evaluated globule size, clarity, permeation (Q1, Q24), and enhancement ratio (ER) across rat skin.

Main Results:

• Optimized microemulsion gel contained 5% oil, 45% SMIX, and 50% water.
• Achieved a significant enhancement ratio (ER) of 37.30 compared to hydrogel.
• Demonstrated significantly higher Cmax, AUC0-24h, and AUC0-∞ than reference formulations.

Conclusions:

• The optimized microemulsion gel formulation successfully enhanced agomelatine permeation and bioavailability.
• Transdermal delivery via microemulsion gel is a viable strategy to overcome agomelatine's oral bioavailability limitations.
• This approach holds potential for improved antidepressant therapy with better systemic exposure.