BACKGROUND AND OBJECTIVES: In order to prolong the action and reduce systemic toxicity, formulations of local anesthetic (LA) complexed with cyclodextrins (CD) have been developed. This study determined the physical-chemical characterization and evaluated the effects of inclusion complexes of racemic bupivacaine (S50-R50) and 50% enantiomeric excess (S75-R25) bupivacaine with hydroxypropil-beta-cyclodextrin (HP-beta-CD) in rats, and comparing them with the solutions currently used in the clinical practice. METHODS: Inclusion complexation of S75-R25 with HP-beta-CD (equimolar ratio 1:1) was characterized by phase-solubility studies varying the concentrations of HP-beta-CD and the temperature. Affinity constants (K) for HP-beta-CD and the thermodynamic parameters for complexation were determined. Motor and sensitive anesthesias were evaluated through the subarachnoid administration of the formulations in the concentration of 0.5%. RESULTS: Inclusion complexation was observed through the increase in aqueous solubility of LA in different temperatures and concentrations of HP-beta-CD. The in vivo tests demonstrated that S50-R50HP-beta-CD and S75-R25HP-beta-CD reduced latency (p < 0.001) without changing the recovery time of the motor block, time for maximal effect, and total effect of the drugs. Besides, both formulations increased the intensity (1.5 times, p < 0.001) and prolonged the duration of analgesia compared to the free drugs. CONCLUSIONS: The complexes S50-R50HP-beta-CD and S75-R25HP-beta-CD potentiated the differential nervous block, and can be used to reduce the frequency of administration or the dose of the LA to induce the same effect. The formulation containing enantiomeric excess (S75-R25) bupivacaine showed to be interesting in the development of safer formulations, and useful for the treatment of acute pain in the postoperative period.
ANESTHETICS, Local; ANIMALS
