title: Rapid human skin permeation and topical anaesthetic activity of a new amethocaine microemulsion.
abstract: We developed a fast-acting, topical, 4% (w/w) amethocaine microemulsion and tested its in vitro permeation in isolated human skin. Comparison with a commercial amethocaine gel (Ametop((R)) ) was performed using Franz diffusion cells. Permeability coefficient (k(p)), flux (J) and percentage permeation after 10 h of microemulsion application were, in all cases, 1.5 times higher than those of the gel. The values obtained for the P(1) parameter [1], 1.06.10(-2) cm (microemulsion) and 0.724.10(-2) cm (gel) indicate that the microemulsion excipients favour amethocaine deposition in the skin, increasing the permeability coefficient, amount of drug retained in the skin, and the flux achieved. Analgesic activity was also examined in rats made hyperalgesic or allodynic after carrageenan-induced inflammation. The rats were distributed into four groups (n = 5-9 per group), each group receiving topically either amethocaine microemulsion, amethocaine gel (Ametop), amethocaine subcutaneous infiltration or nothing (controls). In edematous paws, anti-hyperalgesic activity appeared at 4.2 and 13.8 min after application of amethocaine microemulsion and gel, respectively. These effects are lower than after 0.5% w/w amethocaine infiltration. Amethocaine microemulsion was the only topical formulation with an anti-allodynic effect, although this effect was less than with amethocaine infiltration. These results suggest that microemulsion could be a valuable formula for improving amethocaine permeation and thus bringing rapid pain relief.
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Unitat de Biofarmàcia i Farmacocinètica, Universitat de Barcelona, Spain. eescribano@ub.edu
authors.forename: E
authors.initials: E
authors.lastname: Escribano
authors.forename: M
authors.initials: M
authors.lastname: Obach
authors.forename: M I
authors.initials: MI
authors.lastname: Arévalo
authors.forename: A C
authors.initials: AC
authors.lastname: Calpena
authors.forename: J
authors.initials: J
authors.lastname: Domenech
authors.forename: J
authors.initials: J
authors.lastname: Queralt
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D002351:Carrageenan; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004655:Emulsions; D005260:Female; D005782:Gels; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D051381:Rats; D012867:Skin / Q000187:drug effects*; D012869:Skin Absorption; D012881:Skin Temperature / Q000187:drug effects; D013748:Tetracaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014110:Touch
chemical_list: D000779:Anesthetics, Local; D004655:Emulsions; D005782:Gels; D013748:Tetracaine; D002351:Carrageenan