Budesonide-hydroxypropyl-beta-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels

• Autor(a) principal: Santos Akkari, Alessandra Cristina
• Data de Publicação: 2016
• Outros Autores: Ramos Campos, Estefania Vangelie [UNESP], Keppler, Artur Franz, Fraceto, Leonardo Fernandes [UNESP], Paula, Eneida de, Tofoli, Giovana Radomille, Araujo, Daniele Ribeiro de
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.colsurfb.2015.11.048; http://hdl.handle.net/11449/165036
• topic: Budesonide; Cyclodextrin; Poloxamer; Micelle; Hydrogel; Ulcerative colitis; Polyrotaxane

Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-beta-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-beta-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc = 8662.8 M-1), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-beta-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-beta-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (T-m) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-beta-CD or BUD:HP-beta-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-beta-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-beta-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis. (C) 2015 Elsevier B.V. All rights reserved.