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

Abstract

Our findings indicate that lignocaine base in polar lipids acts as a slow-release preparation of local anaesthetic both in vitro and in vivo.

Local Anesthetics in Lipid-Depot Formulations—Neurotoxicity in Relation to Duration of Effect in a Rat Model

“…However, because depot formulations of local anesthetics are mainly designed to produce reversible nerve blocks for postoperative pain, the findings were troubling and raised the question of whether long duration of action with such formulations must be bought at the price of more or less severe neurotoxicity. This question prompted a second study on formulations that mainly contain bupivacaine as the active substance, in concentrations higher than in licensed preparations, as well as a test of the possible neurotoxicity of some earlier reported formu-lations 21,22 with otherwise promising pharmaceutical and pharmacologic characteristics.…”

“…Furthermore, four previously described formulations were studied: 4.2% and 7.0% of bupivacaine base in MCT, 22 20% lidocaine base in SPC/GD, and pure SPC/GD vehicle. 21 The MCT formulations were prepared by mixing the components in a glass vial and melting to a homogenous transparent liquid, at a maximum temperature of 90°C. They were then cooled in a water bath to 10°C.…”

“…21,22,28,29 The animals were briefly anesthetized with halothane, 2% to 3% in oxygen, by facemask. The sciatic nerve on one side was surgically exposed.…”

“…In the absence of nerve block, the rats withdrew the paw within 3 seconds. 21,22,28,29 Consequently, partial block was defined as a withdrawal latency of 4 to 10 seconds. The duration of sensory block is given as the time from injection of the test formulation to the last occurrence of full and partial block, respectively.…”

“…6,7,10,14,16,17,20,[23][24][25][26]31 Other recently presented depot formulations of local anesthetics are based on oily vehicles prepared from natural lipids. 21,22,28,29,33 The possibility that depot formulations of local anesthetics may be neurotoxic has not received adequate attention in the literature. Ample theoretical reason suggests that they might be.…”