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 th e mobilities of the different]rinds of ionic species appearing in this system was investigated at 25.0 degrees C by precision conductometry. The molar conductivity was determined at several concentration betwee n 0.4 and 10 mM and the data analysed using the conductance equation o f Fuoss-Hsia and Fernandez-Prini (FHFP equation). For concentrations o f up to approximate to 1.2 mM no higher aggregates that LidH(+) were f ound. Using a two-parameter analysis of the equilibrium, LidH(+) doubl e left right arrow Lid + H+, we obtained the acid dissociation constan t, K-a(LidH(+)) = 2.5 . 10(-7) (molar scale); pK(a) = 6.60, and the li miting molar conductivity, lambda(o)(LidH(+)) = 0.2675 cm(2)/Omega per mel. For concentrations above 1.2 mM there is strong evidence of form ation of ion-pairs, LidH(+) Cl-. The ion-pair association constant was estimated to K(p)approximate to 40 indicating that about 15% of the e lectrolyte is in the form of LidH(+)Cl(-) at the highest concentration (10 mM) investigated. (C) 1998 Elsevier Science B.V. All rights reser ved.