New insights into eutectic cream skin penetration enhancement

Area of Science:

• Pharmacology
• Physical Chemistry
• Dermatology

Background:

• The mechanism by which EMLA (eutectic mixture of local anesthetics) enhances lidocaine and prilocaine penetration into human skin remains unclear.
• Understanding drug aggregation and its role in percutaneous delivery is crucial for optimizing topical anesthetic formulations.

Purpose of the Study:

• To investigate the role of drug aggregation modification in EMLA's enhanced percutaneous delivery of lidocaine and prilocaine.
• To characterize the aggregation behavior of lidocaine and prilocaine, individually and in combination, in aqueous solutions.

Main Methods:

• Light scattering analysis was employed to determine the critical aggregation concentration (CAC) and mean aggregate size of lidocaine and prilocaine.
• The effect of the surfactant polyoxyethylene hydrogenated castor oil, present in EMLA, on drug aggregation was evaluated.

Main Results:

• Lidocaine exhibited a CAC of 572 μM and a mean aggregate size of 58.8 nm.
• Prilocaine showed a CAC of 1177 μM and a mean aggregate size of 105.7 ± 24.8 nm.
• In a 1:1 eutectic ratio, lidocaine-prilocaine aggregation reduced significantly (CAC 165.8 μM, aggregate size 43.82 nm), further decreasing to <20 nm with the addition of the EMLA surfactant.

Conclusions:

• The surfactant in EMLA cream plays a key role in modifying lidocaine-prilocaine interactions and reducing aggregate size.
• This surfactant-induced modification of drug aggregation facilitates a six-fold increase in drug penetration through human epidermal tissue compared to oil formulations.