title: The dermal delivery of lignocaine: influence of ion pairing.
abstract: The purpose of the present study was to determine the significance of ion pairing on the permeation of lignocaine. Results of diffusion studies through polydimethylsiloxane (PDMS) at different pH values 4. 0, 6.0, 7.0, 8.0 indicated that lignocaine hydrochloride (L-HCl) flux significantly increased with the amount of unionized base. In order to see if similar results could be obtained using human skin, permeation runs were performed with human skin at pH of 4.0, 5.5 and 7.0. These values were chosen to simulate an appropriate range of physiological conditions. Results of the experiments with human epidermis showed increasing L-HCl flux with increasing pH, confirming the trends seen with PDMS membranes. A linear relationship was found between the apparent partition coefficient and the steady state flux. Further experiments were conducted at donor pH 4.0 to minimise the contribution of the unionized species. Although an excess of different ions such as nitrate, mesylate and bromide increased the apparent partition coefficient, the steady state flux was not significantly increased. The steady state lignocaine flux was increased up to 2.45-fold using different counter ions. The highest flux was measured from lignocaine morpholinopropane sulfonate (L-mps). It is possible to enhance the flux of salts across lipophilic membranes by using an ion pair approach. The degree to which this is possible depends on the lipophilicity of the counter ion, the medium in which the ion pair forms, and the ionic strength.
authors.affiliation: Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria. claudia.valenta@univie.ac.at
authors.forename: C
authors.initials: C
authors.lastname: Valenta
authors.forename: U
authors.initials: U
authors.lastname: Siman
authors.forename: M
authors.initials: M
authors.lastname: Kratzel
authors.forename: J
authors.initials: J
authors.lastname: Hadgraft
mesh_terms: D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001565:Benzoates; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007477:Ions; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008567:Membranes, Artificial; D009566:Nitrates; D012869:Skin Absorption; D012995:Solubility; D013451:Sulfonic Acids
chemical_list: D000779:Anesthetics, Local; D001565:Benzoates; D007477:Ions; D008567:Membranes, Artificial; D009566:Nitrates; D013451:Sulfonic Acids; D008012:Lidocaine