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

• Published in: International journal of pharmaceutics 1998-06, Vol.168 (1), p.85-95
• Main Authors: Karami, Kiomars, Beronius, Per
• Format: Article
• Language: English
• Subjects: Anesthetics. Neuromuscular blocking agents; Biological and medical sciences; Enhancer; General pharmacology; Ion pairs; Ionic conductivity; Iontophoresis; Lidocaine hydrochloride; Medical sciences; Molar conductivity; Neuropharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propylene glycol
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00090-8

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); p K a=6.60, and the limiting molar conductivity, λ 0(LidH +)=0.2675 cm 2/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.