Sufentanil-2-hydroxypropyl-beta-cyclodextrin inclusion complex for pain treatment: Physicochemical, cytotoxicity, and pharmacological evaluation

Author(s):Show less -

Volobuef, Cristiane ^[1] ; Moraes, Carolina M. ^[1] ; Nunes, Lazaro A. S. ^[1] ; Cereda, Cintia M. S. ^[1] ; Yokaichiya, Fabiano ^[2] ; Franco, Margareth K. K. D. ^[2] ; Braga, Angelica F. A. ^[3] ; De Paula, Eneida ^[1] ; Tofoli, Giovana Radomille ^[4] ; Fraceto, Leonardo F. ^{[1, 5]} ; De Araujo, Daniele R. ^{[1, 6]}

Affiliation

^[1] Univ Estadual Campinas, Dept Bioquim, Inst Biol, Sao Paulo - Brazil

^[2] Lab Nacl Luz Sincrotron, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Dept Anestesiol, Fac Ciencias Med, Sao Paulo - Brazil

^[4] Univ Sao Francisco, Unidade Gastroenterol & Farmacol Clin, Sao Paulo - Brazil

^[5] Univ Estadual Julio de Mesquita Filho UNESP, Dept Engn Ambiental, Sao Paulo - Brazil

^[6] Univ Fed ABC, Ctr Ciencias Nat & Humanas, UFABC, BR-09210170 Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Pharmaceutical Sciences; v. 101, n. 10, p. 3698-3707, OCT 2012.
• Web of Science Citations: 6

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-beta-cyclodextrin (HP-beta-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 (Ka) value of 515.2 +/- 1.2?M-1 between SUF and HP-beta-CD. Complexation with HP-beta-CD protected SUF from light exposure and increased its photostability. Release kinetics revealed a decrease in SUF release rate (Krel = 7.05 +/- 0.52 and 5.61 +/- 0.39?min-1/2 for SUFHP-beta-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-beta-CD (355.7 +/- 47.2?min) when injected at the same dose (1 mu g 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. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:36983707, 2012 (AU)

• FAPESP's process: 06/00121-9 - New formulations for the controlled release of local anesthetics in dentistry: from development to clinical tests
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/11475-1 - Development and pharmacological evaluation of drug-delivery systems containing tramadol in thermoreversible hydrogels for pain treatment
• Grantee: Daniele Ribeiro de Araujo
• Support Opportunities: Regular Research Grants