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

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

JOURNAL OF MOLECULAR LIQUIDS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; 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 forimproving 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 compoundsin 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 to