Interaction pathways of specific co-solvents with hydroxypropyl-β-cyclodextrin inclusion complexes with benznidazole in liquid and solid phase

DE MELO, POLYANNE N.; BARBOSA, EUZÉBIO G.; GARNERO, CLAUDIA; DE CALAND, LILIA B.; FERNANDES-PEDROSA, MATHEUS F.; LONGHI, MARCELA R.; DA SILVA-JÚNIOR, ARNÓBIO ANTÔNIO

JOURNAL OF MOLECULAR LIQUIDS

ELSEVIER SCIENCE BV

Año: 2016 vol. 223 p. 350 - 350

0167-7322

he main purpose of the study was to assess the mechanism whereby the co-solvents triethanolamine (TEA) and 1-methyl-2-pyrrolidone (NMP) interacted with hydroxypropyl-beta-cyclodextrin (HP-β-CD) in ternary associations for improving the solubility and dissolution rate of the insoluble ingredient benznidazole (BNZ). In liquid phase, the solubility diagrams and Job´s plot results were further explored by in silico molecular modeling and experimental 1H NMR spectroscopy studies. The structure of the inclusion complexes in the binary and ternary association were established. The competition of NMP with the drug for the HP-β-CD cavity was evidenced, while TEA stabilized the drug-CD interactions, forming ternary complexes. FTIR analysis confirmed distinct intermolecular interactions among the compounds in the different solid dispersions prepared by physical mixture (PM) and spray drying (SD). The co-solvents improved the drug dissolution performance from PM ternary associations due