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 nerve 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 dexamethasone into the system. Methods: In vitro release of lignocaine from the lipid formulation was studied in a US Pharmacopoeia rotating apparatus. Sciatic nerve blocks were induced 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 lipid formulation or the last formulation with dexamethasone 0.05, 0.5 or 5 mg.ml(-1). The durations of sensory and motor block and the arterial blood concentrations of lignocaine were investigated. Results: In vitro there was a sustained release of lignocaine from the lipid formulation, with 50% release at around 48 h. In vivo lignocaine base 20 mg.ml(-1) in lipid formulation produced sciatic nerve blocks of significantly shorter duration than lignocaine HCl 20 mg.ml(-1) in aqueous solution, while lignocaine base 100 and 200 mg.ml(-1) in lipid formulation produced blocks lasting two and three times longer, respectively, than the lignocaine HCl solution. Addition of dexamethasone did not affect the duration of nerve block. Following administration of lignocaine base 200 mg.ml(-1) in lipid formulation, as compared to lignocaine HCl 20 mg.ml(-1) in aqueous solution, the maximal blood concentration of lignocaine was only three times higher in spite of the ten-fold difference in dose, and the mean terminal half-life was three times longer, reflecting the slow release from the formulation. Conclusions: Our findings indicate that lignocaine base in polar lipids acts as a slow-release preparation of local anaesthetic both in vitro and in vivo.