On iontophoretic delivery enhancement: Ionization and mobility of lidocaine hydrochloride in propylene glycol

The structure of lidocaine hydrochloride (LidHCl) in propylene glycol (PG), a solvent known to enhance transdermal delivery of drugs, and the mobilities of the different kinds of ionic species appearing in this system was investigated at 25.0°C by precision conductometry. The molar conductivity was determined at several concentration between 0.4 and 10 mM and the data analysed using the conductance equation of Fuoss-Hsia and Fernandez-Prini (FHFP equation). For concentrations of up to ≈1.2 mM no higher aggregates that LidH⁺ were found. Using a two-parameter analysis of the equilibrium, LidH⁺⇔Lid+H⁺, we obtained the acid dissociation constant, K_a(LidH⁺)=2.5·10⁻⁷ (molar scale); pK_a=6.60, and the limiting molar conductivity, λ₀(LidH⁺)=0.2675 cm²/Ω per mol. For concentrations above 1.2 mM there is strong evidence of formation of ion-pairs, LidH⁺Cl⁻. The ion-pair association constant was estimated to K_p≈40 indicating that about 15% of the electrolyte is in the form of LidH⁺Cl⁻ at the highest concentration (10 mM) investigated.