Sufentanil-2-hydroxypropyl-β-cyclodextrin inclusion complex for pain treatment: physicochemical, cytotoxicity, and pharmacological evaluation.

Cristiane Volobuef, Carolina M Moraes, Lázaro A S Nunes, Cíntia M S Cereda, Fabiano Yokaichiya, Margareth K K D Franco, Angélica F A Braga, Eneida De Paula, Giovana Radomille Tófoli, Leonardo F Fraceto, Daniele R De Araujo

Index: J. Pharm. Sci. 101(10) , 3698-707, (2012)

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Abstract

Sufentanil (SUF) is a synthetic analgesic opioid widely used for the management of acute and chronic pain. This drug was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and the physicochemical characterization, in vitro/ex vivo toxicity assays, and pharmacological evaluation were performed. Differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR) analysis, and X-ray powder diffraction showed the formation and the morphology of the complex. Nuclear magnetic resonance afforded data regarding inclusion complex stoichiometry (1:1) with an association binding constant (K(a)) value of 515.2 ± 1.2 M(-1) between SUF and HP-β-CD. Complexation with HP-β-CD protected SUF from light exposure and increased its photostability. Release kinetics revealed a decrease in SUF release rate (K(rel) = 7.05 ± 0.52 and 5.61 ± 0.39 min(-1/2) for SUF-HP-β-CD and SUF, respectively) and reduced hemolytic or myotoxic effects after complexation. Time course of tail-flick test showed that the duration of analgesia induced by SUF (150.0 ± 34.6 min) was significantly increased (p < 0.001) after complexation with HP-β-CD (355.7 ± 47.2 min) when injected at the same dose (1 μg kg(-1)), prolonging the duration of analgesia after intramuscular administration and representing an alternative on the development of effective and safe drug-delivery system for opioid analgesics.Copyright © 2012 Wiley Periodicals, Inc.