Host-guest interactions between benznidazole and beta-cyclodextrin in multicomponent complex systems involving hydrophilic polymers and triethanolamine in aqueous solution

P. DE MELO; E. BARBOSA; C. GARNERO; M. LONGHI; M. FERNANDES-PEDROSA; A. DA SILVA-JUNIOR

JOURNAL OF MOLECULAR LIQUIDS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2013 vol. 186 p. 147 - 156

0167-7322

Association of hydrophilic compounds with cyclodextrins to increase drug solubility has been extensively studied in aqueous solution. However, the mechanism of interaction among these components remains unclear. In this study, the effect of seven different hydrophilic polymers (HPs) and triethanolamine (TEA) isolated or associated with beta-cyclodextrin (-CD) in the aqueous solubility of benznidazole (BNZ) was investigated using a multicomponent complex approach. The UV spectrophotometric method used for quantitative analysis of BNZ was validated in -CD, TEA and HPs presence. Solubility diagrams in different pH values confirmed linear soluble BNZ--CD inclusion complexes, with 1:1 stoichiometry (AL type). Addition of HPs contributed to stability of BNZ--CD complexes. This improvement was thermodynamically favorable, probably due to entropy reduction caused by presence of HPs. The higher TEA concentration (40% w/v) investigated promoted a solubility increment of almost five-times. The TEA association with -CD leads to formation of inclusion complexes with limited solubility (B type). Phase solubility study of BNZ in isolated TEA solutions suggested a cosolvency involvement. This affirmation was supported by molecular modeling studies and confirmed by NMR studies.