title: Evaluation of chemical enhancers in the transdermal delivery of lidocaine.
abstract: The effect of various classes of chemical enhancers was investigated for the transdermal delivery of the anesthetic lidocaine across pig and human skin in vitro. The lipid disrupting agents (LDA) oleic acid, oleyl alcohol, butenediol, and decanoic acid by themselves or in combination with isopropyl myristate (IPM) showed no significant flux enhancement. However, the binary system of IPM/n-methyl pyrrolidone (IPM/NMP) improved drug transport. At 2% lidocaine dose, this synergistic enhancement peaked at 25:75 (v/v) IPM:NMP with a steady state flux of 57.6 +/- 8.4 microg cm(-2) h(-1) through human skin. This observed flux corresponds to a four-fold enhancement over a 100% NMP solution and over 25-fold increase over 100% IPM at the same drug concentration (p < 0.001). NMP was also found to co-transport through human skin with lidocaine free base and improve enhancement due to LDA. These findings allow a more rational approach for designing oil-based formulations for the transdermal delivery of lidocaine free base and similar drugs.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lee
authors.forename: Naina
authors.initials: N
authors.lastname: Ahmad
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
authors.forename: V
authors.initials: V
authors.lastname: Prasad Shastri
mesh_terms: D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004338:Drug Combinations; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D009226:Myristates / Q000008:administration & dosage / Q000494:pharmacology; D010592:Pharmaceutic Aids / Q000008:administration & dosage / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D004338:Drug Combinations; D009226:Myristates; D010592:Pharmaceutic Aids; D011760:Pyrrolidinones; C008205:isopropyl myristate; D008012:Lidocaine; C038678:N-methylpyrrolidone