title: New insights into eutectic cream skin penetration enhancement.
abstract: The manner in which the eutectic cream EMLA enhances the percutaneous penetration of lidocaine and prilocaine into human skin is still not fully understood. The purpose of this study was to investigate if the modification of drug aggregation played a role in the way EMLA facilitates delivery. Light scattering analysis of lidocaine alone in water gave a critical aggregation concentration (CAC) of 572 μM and a mean aggregate size of 58.8 nm. The analysis of prilocaine in identical conditions gave a CAC of 1177 μM and a mean aggregate size of 105.7 ± 24.8 nm. When the two drugs were mixed at their eutectic 1:1 ratio in water the CAC reduced to 165.8 μM and the aggregate size was 43.82 nm. This lidocaine-prilocaine interaction in water was further modified upon addition of polyoxyethylene hydrogenated castor oil, the surfactant in the EMLA aqueous phase, to produce aggregates of <20 nm. The physical characterisation data suggested that it was the EMLA cream's surfactant that modified the drug molecular interactions in the aqueous continuous phase and caused a 6 fold higher drug penetration through human epidermal tissue compared to the oil formulations tested in this study.
authors.affiliation: Insitute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Fiala
authors.affiliation: Insitute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Marie
authors.initials: M
authors.lastname: Roman
authors.affiliation: Insitute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Inacio
authors.affiliation: Insitute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Sumaia
authors.initials: S
authors.lastname: Mashal
authors.affiliation: School of Pharmacy, University of Hertfordshire, College Lane, Hatfield, Herts, AL10 9AB, United Kingdom; MedPharm Ltd., Unit 3/Chancellor Court, 50 Occam Road, Surrey Research Park, Guilford GU2 7YN, United Kingdom.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Brown
authors.affiliation: Insitute of Pharmaceutical Science, School of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom. Electronic address: stuart.jones@kcl.ac.uk.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Jones
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002368:Castor Oil / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077442:Lidocaine, Prilocaine Drug Combination; D011318:Prilocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D063465:Skin Cream; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000779:Anesthetics, Local; D000077442:Lidocaine, Prilocaine Drug Combination; D013501:Surface-Active Agents; D011318:Prilocaine; C023040:polyethoxylated castor oil; D002368:Castor Oil; D008012:Lidocaine
keywords: EMLA(®); Eutectic; Lidocaine; Penetration enhancement; Prilocaine; Skin