Triethanolamine Stabilization of Methotrexate-B-Cyclodextrin Interactions in Ternary Complexes

JAHAMUNNA A. A. BARBOSA; ARIANA ZOPPI; ARIANA ZOPPI, MARIO A. QUEVEDO, MARCELA R. LONGHI; POLYANNE N. DE MELO; ARTHUR S. A. DE MEDEIROS; LETÍCIA STRECK; ALICE R. DE OLIVEIRA; MATHEUS F. FERNANDES-PEDROSA; MARCELA R. LONGHI; ARNÓBIO A. DA SILVA-JÚNIOR

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2014 vol. 15 p. 17077 - 17077

he interaction of methotrexate (MTX) with B-cyclodextrin (B-CD) in the presence of triethanolamine (TEA) was investigated with the aim to elucidate the mechanism whereby self-assembly cyclodextrin systems work in association with this third component.Solubility diagram studies showed synergic increment of the MTX solubility to be about thirty-fold. Experiments using 2D ROESY and molecular modeling studies revealed the inclusion of aromatic ring III of the drug into B-CD cavity, in which TEA contributes by intensifying MTX interaction with B-CD and stabilizes MTX:B-CD:TEA ternary complex by electrostatic interaction. The maintenance of these interactions in solid phase was also studied in ternary MTX:B-CD:TEA and comparisons were made with freeze dried binary MTX:B-CD and physical mixtures. FTIR studies evidenced that MTX B-CD interaction remained in solid ternary complexes, which was also supported by thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TG)/