Triethanolamine stabilization of methotrexate-β-cyclodextrin interactions in ternary complexes

BARBOSA J.A.A; ZOPPI, A.; QUEVEDO, M.A.; DE MELO, P.N.; DE MEDEIROS; STRECK, L.; OLIVEIRA, A.R.; FERNANDES-PEDROSA, M.; LONGHI, M.R.; DA SILVA-JÚNIOR, A.

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

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

he interaction of methotrexate (MTX) with beta-cyclodextrin (β-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 β-CD cavity, in which TEA contributes by intensifying MTX interaction with β-CD and stabilizes MTX:β-CD:TEA ternary complex by electrostatic interaction. The maintenance of these interactions in solid phase was also studied in ternary MTX:β-CD:TEA and comparisons were made with freeze dried binary MTX:β-CD and physical mixtures. FTIR studies evidenced that MTX?β-CD interaction remained in solid ternary complexes, which was also supported by thermal (differential scanning calorimetry (D