Inclusion of lignocaine base into a polar lipid formulation - in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat
H. Dyhre et al., Inclusion of lignocaine base into a polar lipid formulation - in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat, ACT ANAE SC, 45(5), 2001, pp. 583-589
Citations number
17
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
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.