title: Dynamic in-situ eutectic formation for topical drug delivery.
abstract: OBJECTIVE
  The relationship between the solution-state chemistry of eutectic systems and their transmembrane transport characteristics is difficult to define as these mixtures are sensitive to delivery vehicle-induced penetration enhancement. Through in-situ formation of a molten eutectic mixture using highly evaporative sprays this study aimed to gain an understanding of solution-state thermodynamic and chemical properties of eutectic combinations pertinent to transmembrane transport in the absence of a delivery vehicle.
  
  
  METHODS
  In-situ molten lidocaine-prilocaine eutectics were formed using a hydroflouroalkane (HFA) propellant. Transport through silicone membranes and human skin in upright Franz diffusion cells was determined using in-house manufactured creams as controls.
  
  
  RESULTS
  The application of the two drugs in an HFA spray produced a molten oil even when the melting point of the drug mixture was above the experimental temperature at the membrane surface. In the absence of vehicle effects, molecule presentation to the membrane interface was most effective using a lidocaine-rich mixture of 0.7% w/w lidocaine:prilocaine - 1985.06 ± 128.87 µg/h/cm(2).
  
  
  CONCLUSIONS
  There appeared to be no link between melting point and transmembrane transport of lidocaine:prilocaine from a eutectic mixture. The rate of drug presentation to the membrane interface, which was highest in drug-rich, high-activity molten eutectic mixtures, was the driver for transmembrane transport in the absence of significant barrier interactions.
authors: Institute of Pharmaceutical Science, King's College London, London, UK.
authors: Sarah
authors: S
authors: Fiala
authors: Marc B
authors: MB
authors: Brown
authors: Stuart A
authors: SA
authors: Jones
mesh_terms: D000279:Administration, Cutaneous; D019162:Anesthetics, Combined / Q000378:metabolism*; D000779:Anesthetics, Local / Q000378:metabolism*; D001692:Biological Transport; D016503:Drug Delivery Systems; D006801:Humans; D008012:Lidocaine / Q000378:metabolism*; D000077442:Lidocaine, Prilocaine Drug Combination; D011318:Prilocaine / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
chemical_list: D019162:Anesthetics, Combined; D000779:Anesthetics, Local; D000077442:Lidocaine, Prilocaine Drug Combination; D011318:Prilocaine; D008012:Lidocaine