Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex
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Data
2008-01-01
Autores
de Araujo, Daniele R.
Tsuneda, Simone S.
Cereda, Cintia M. S.
Carualho, Fernanda Del G. F.
Prete, Paulo S. C.
Fernandes, Sergio A.
Yokaichiya, Fabiano
Franco, Margareth K. K. D.
Mazzaro, Irineu
Fraceto, Leonardo F. [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Elsevier B.V.
Resumo
Ropivacaine (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-P-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 11.2 mM for RVC and RVCHP-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 RVCHP-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 RVCHP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation. (c) 2007 Elsevier B.V All rights reserved.
Descrição
Palavras-chave
local anesthetic, ropivacaine, cyclodextrin, analgesia, drug-delivery
Como citar
European Journal of Pharmaceutical Sciences. Amsterdam: Elsevier B.V., v. 33, n. 1, p. 60-71, 2008.