epsilon-Aminocaproic acid esters as transdermal penetration enhancing agents

Area of Science:

• Pharmaceutical Sciences
• Dermal Drug Delivery
• Medicinal Chemistry

Background:

• Theophylline is a widely used bronchodilator with poor skin permeability.
• Enhancing transdermal drug delivery is crucial for effective topical and systemic therapies.
• Azone is a known penetration enhancer, but its efficacy and safety profile can be improved.

Purpose of the Study:

• To synthesize and evaluate novel epsilon-aminocaproic acid esters as potential penetration enhancers for theophylline.
• To compare the efficacy of these novel esters with Azone in enhancing theophylline transport across human cadaver skin.
• To assess the in vitro safety profile of the synthesized compounds.

Main Methods:

• Synthesis of five 1-alkyl epsilon-aminocaproic acid esters, focusing on 1-octyl- (OCEAC) and 1-dodecyl- (DDEAC).
• In vitro evaluation of OCEAC and DDEAC as penetration enhancers for theophylline across excised human cadaver skin.
• Comparison of drug flux and enhancement factors against controls and Azone in various vehicles (olive oil, water, water-propylene glycol).
• Assessment of acute toxicity (LD50) in mice and dermal irritation in rabbits.

Main Results:

• OCEAC and DDEAC demonstrated significant enhancement of theophylline transport, with flux increases ranging from 17 to 45 times compared to controls.
• Both esters showed markedly higher enhancement factors than Azone under tested conditions.
• OCEAC and DDEAC exhibited favorable toxicity profiles, with LD50 values comparable to or better than Azone.
• No acute dermal irritation was observed in rabbits at a 5% concentration.

Conclusions:

• 1-octyl- and 1-dodecyl-epsilon-aminocaproic acid esters are effective and safe penetration enhancers for theophylline.
• These novel esters represent promising alternatives to Azone for improving transdermal drug delivery.
• Further research into their application in pharmaceutical formulations is warranted.