Artículos de revistas
Poloxamer-based Binary Hydrogels For Delivering Tramadol Hydrochloride: Sol-gel Transition Studies, Dissolution-release Kinetics, In Vitro Toxicity, And Pharmacological Evaluation
Registro en:
Poloxamer-based Binary Hydrogels For Delivering Tramadol Hydrochloride: Sol-gel Transition Studies, Dissolution-release Kinetics, In Vitro Toxicity, And Pharmacological Evaluation. Dove Medical Press Ltd, v. 10, p. 2391-2401 2015.
1178-2013
WOS:000351616800001
10.2147/IJN.S72337
Autor
Mendonca dos Santos
Ana Claudia; Santos Akkari
Alessandra Cristina; Silva Ferreira
Iasmin Rosanne; Maruyama
Cintia Rodrigues; Pascoli
Monica; Guilherme
Viviane Aparecida; de Paula
Eneida; Fraceto
Leonardo Fernandes; de Lima
Renata; Melo
Patricia da Silva; de Araujo
Daniele Ribeiro
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407-PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug-micelle interaction studies showed the formation of PL 407-PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407-PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%-45% of the gel dissolved, reaching similar to 80%-90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower K-rel values were observed for PL 407 (20%, K-rel = 112.9 +/- 10.6 mu g . h(-1/2)) and its binary systems PL 407-PL 188 (25%-5% and 25%-10%, K-rel = 80.8 +/- 6.1 and 103.4 +/- 8.3 mu g.h(-1/2), respectively) in relation to TR solution (K-rel = 417.9 +/- 47.5 mu g.h(-1/2), P<0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes) and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects (>72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain. 10
2391 2401 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) FAPESP [2006/00121-9, 2010/11475-1, 2010/13088-5] CNPq [487619/2012-9, 300952/2010-4, 309612/2013-6]