• Daniele R de Araujo, Simone S Tsuneda, Cíntia M S Cereda, Fernanda Del G F Carvalho, Paulo S C Preté, Sergio A Fernandes, Fabiano Yokaichiya, Margareth K K D Franco, Irineu Mazzaro, Leonardo F Fraceto, Angélica de F A Braga, and Eneida de Paula.
• Department of Biochemistry, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
• Eur J Pharm Sci. 2008 Jan 1; 33 (1): 60-71.

AbstractRopivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used in surgical procedures, which presents physico-chemical and therapeutic properties similar to those of bupivacaine (BPV), but associated to less systemic toxicity. This study focuses on the development and pharmacological evaluation of a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) inclusion complex. Phase-solubility diagrams allowed the determination of the association constant between RVC and HP-beta-CD (9.46 M(-1)) and showed an increase on RVC solubility upon complexation. Release kinetics revealed a decrease on RVC release rate and reduced hemolytic effects after complexation (onset at 3.7 mM and 11.2mM for RVC and RVC HP-beta-CD, respectively) were observed. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray) showed the formation and the morphology of the complex. Nuclear magnetic resonance (NMR) and job-plot experiments afforded data regarding inclusion complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed that RVC HP-beta-CD was able to reduce the latency without increasing the duration of motor blockade, but prolonging the duration and intensity of the sensory blockade (p<0.001) induced by the LA in mice. These results identify the RVC HP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation.

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