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

J. BARBOSA; A. ZOPPI; M. QUEVEDO; P. DE MELO; A. DE MEDEIROS; A. GOMES DE OLIVEIRA; M. FERNANDES-PEDROSA; M. LONGHI; A. DA SILVA-JUNIOR; J. BARBOSA; A. ZOPPI; M. QUEVEDO; P. DE MELO; A. DE MEDEIROS; A. GOMES DE OLIVEIRA; M. FERNANDES-PEDROSA; M. LONGHI; A. DA SILVA-JUNIOR

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2014 vol. 15 p. 17077 - 17099

1422-0067

Methotrexate (MTX) is a chemotherapic and antipsoriatic with a low transdermal permeation, which limits its success in local treatment of psoriasis or skin tumors. MTX-loaded beta-cyclodextrin (-CD) freeze dried complexes in binary or ternary complexes adding triethanolamine (TEA) were obtained with aim to increase the non ionized drug fraction in solution. The interaction among components in solution was well studied using solubility diagrams, molecular modeling and nuclear resonance magnetic NMR studies, which demonstrated obtainment of stable soluble inclusion complexes AL type, with K1:1, in which the presence of TEA raised -CD effect. These experimental results were used to obtain binary and ternary freeze dried complexes, which were well characterized by electronic microscopy (SEM), drug loading analysis, infrared spectroscopy, thermal analysis (differential scanning calorimetry DSC, thermogravimetric analysis (TG)/ first derivative of TG analysis DTG and C,N,H elementary analysis), X-ray diffraction analysis (DRX) and dissolution studies. The solution studies demonstrated a strong interaction between MTX with -CD by real inclusion of drug into both binary and ternary complexes, which were supported by solid studies. The success of freeze dried complexes was finally confirmed by dissolution studies, which reveal a statiscally superior performance of binary and ternary complexes again pure drug. Moreover, TEA presence in ternary complexes may potentially act as permeation agent.