Bupivacaine containing dry emulsion can prolong epidural anesthetic effects in rabbits.
To assess the prolongation of epidural bupivacaine by a novel lipid formulation, a physically stabilized bupivacaine containing dry emulsion was prepared by spray-drying. Bupivacaine release from the oil-in-water emulsion was studied using an in vitro two-phase stirred model, then the pharmacodynamic effects and the pharmacokinetics of bupivacaine from the spray-dried emulsion were evaluated and compared to a bupivacaine hydrochloride solution, following a two-period cross-over epidural administration in rabbits. The in vitro release characteristics suggested an extended release of bupivacaine from the emulsion compared to the solution. From the in vivo study, C(max) obtained with the emulsion (containing 5 mg bupivacaine) was not statistically different than from the solution (containing 2 mg bupivacaine) while T(max) was increased, suggesting a diminution of bupivacaine systemic absorption. The onset time of epidural anesthesia was similar for both formulations of bupivacaine used, while a significant blockade prolongation (360%) was observed with the emulsion compared to the solution, suggesting a controlled release of bupivacaine. Dry emulsions could be promising dosage forms to optimize the disposition of epidurally administered LAs.
Dollo
G
G
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex, France. gilles.dollo@univ-rennes1.fr
Le Corre
P
P
Chevanne
F
F
Le Verge
R
R
D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004655:Emulsions; D066298:In Vitro Techniques; D009043:Motor Activity; D010316:Particle Size; D011817:Rabbits; D013997:Time Factors
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D004655:Emulsions; D002045:Bupivacaine