Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

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Araujo, Daniele R. de ; Tsuneda, Simone S. ; Cereda, Cíntia M. S. ; Carvalho, Fernanda Del G. F. ; Preté, Paulo S. C. ; Fernandes, Sergio A. ; Yokaichiya, Fabiano ; Franco, Margareth K. K. D. ; Mazzaro, Irineu ; Fraceto, Leonardo F. ; et al

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmaceutical Sciences; v. 33, n. 1, p. 60-71, Jan. 2008.
• Área do conhecimento: Ciências da Saúde - Odontologia
• Assunto(s): Analgesia Sistemas de liberação de medicamentos Anestésicos locais Ciclodextrinas Ropivacaína

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. (AU)

• Processo FAPESP: 01/12476-2 - Formulações de liberação controlada com anestésicos locais amino-amidas cíclicos: preparação, caracterização e ensaios farmacológicos
• Beneficiário: Daniele Ribeiro de Araujo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 01/03746-6 - Desenvolvimento de formulações anestésicas de liberação controlada
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Regular