Percutaneous absorption-enhancing activity of urea derivatives

Area of Science:

• Dermatology
• Pharmaceutics
• Drug Delivery

Background:

• Percutaneous absorption of drugs is crucial for topical and transdermal therapies.
• Enhancing drug penetration through the stratum corneum remains a significant challenge in formulation development.

Purpose of the Study:

• To investigate the impact of urea and urea derivatives on the percutaneous absorption of salicylic acid and sodium salicylate.
• To evaluate the potential of these compounds as penetration enhancers in petrolatum-based ointments.

Main Methods:

• Rabbit skin was used to assess percutaneous absorption of salicylic acid and sodium salicylate from petrolatum ointments.
• Varying concentrations of urea and different urea derivatives were incorporated into the ointment base.
• Skin irritation tests were conducted to assess the safety of the enhancers.

Main Results:

• Urea and urea derivatives significantly increased the percutaneous absorption of both salicylic acid and sodium salicylate.
• The enhancement effect was dose-dependent, increasing with higher concentrations of the additives.
• Urea derivatives with longer and more numerous alkyl substituents exhibited stronger absorption-enhancing activities.
• The mechanism is attributed to the interaction of urea compounds with stratum corneum lipids and proteins, causing tissue swelling and reduced barrier function.

Conclusions:

• Urea and its derivatives are effective enhancers of percutaneous drug absorption.
• The efficacy of urea derivatives as enhancers correlates with their alkyl substituent characteristics.
• These compounds demonstrate a favorable safety profile, being non-irritating to the skin.
• Urea derivatives show significant potential for development as novel percutaneous absorption enhancers in pharmaceutical formulations.