Inclusion of lignocaine base into a polar lipid formulation - in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat

Background: Slow-release formulations of local anaesthetics may produce ner ve blocks of long duration. The present study aimed at investigating the in vitro and in vivo properties of a polar lipid formulation for slow release of lignocaine and the effects on nerve block duration by inclusion of dexa methasone into the system. Methods: In vitro release of lignocaine from the lipid formulation was stud ied in a US Pharmacopoeia rotating apparatus. Sciatic nerve blocks were ind uced in rats by 0.1 mi of test formulations containing lignocaine HCl 20 mg .ml(-1) in aqueous solution, lignocaine base 20, 100 or 200 mg.ml(-1) in li pid formulation or the last formulation with dexamethasone 0.05, 0.5 or 5 m g.ml(-1). The durations of sensory and motor block and the arterial blood c oncentrations of lignocaine were investigated. Results: In vitro there was a sustained release of lignocaine from the lipi d formulation, with 50% release at around 48 h. In vivo lignocaine base 20 mg.ml(-1) in lipid formulation produced sciatic nerve blocks of significant ly shorter duration than lignocaine HCl 20 mg.ml(-1) in aqueous solution, w hile lignocaine base 100 and 200 mg.ml(-1) in lipid formulation produced bl ocks lasting two and three times longer, respectively, than the lignocaine HCl solution. Addition of dexamethasone did not affect the duration of nerv e block. Following administration of lignocaine base 200 mg.ml(-1) in lipid formulation, as compared to lignocaine HCl 20 mg.ml(-1) in aqueous solutio n, the maximal blood concentration of lignocaine was only three times highe r in spite of the ten-fold difference in dose, and the mean terminal half-l ife was three times longer, reflecting the slow release from the formulatio n. Conclusions: Our findings indicate that lignocaine base in polar lipids act s as a slow-release preparation of local anaesthetic both in vitro and in v ivo.