Synthesis and in vitro skin permeation study of lidocaine organic salits

Abstract

Organic quarternary ammonium salts of lidocaine were designed and synthesized in this research study. The synthesized compounds were regarded as prodrugs of lidocaine and were expected to enhance skin permeability by ion-pair mechanism. Four organic salts were lidocaine adipate, lidocaine maleate, lidocaine malonate and lidocaine tosylate. In vitro permeation study through pig skin and determination of partition coefficients were carried out. First derivative UV spectrophotometry was employed to quantitate the permeated amount. The skin permeabilities were calculated as cumulative amount (Q) and flux (J). The skin permeation of lidocaine adipate and lidocaine malonate after 12 hours of application were significantly higher than lidocaine hydrochloride but was not significantly different from lidocaine (α < 0.05). The increase in permeation of organic salts from lidocaine hydrochloride and the different profile of permeation from lidocaine may be the result of prodrug structure contributing ion-pair transportation besides normal route of transportation.