RESUMO
2-Hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (1), an antibacterial agent, was shown to form inclusion complexes with HP-beta-CD in aqueous solution. In the present work the kinetics of 1 degradation in aqueous buffer solution was investigated as a function of pH (2.34-3.95), HP-beta-CD concentration (0%-28% (w/v)) and temperature (60-90 degrees C). A second-order derivative spectroscopic methodology was developed for the kinetic investigations. The degradation showed to follow pseudo-first-order kinetics. Also, an specific acid catalysis was found and the introduction of up to 28% (w/v) HP-beta-CD to the reaction medium did not change this kinetic behaviour. The obtained results indicated that HP-beta-CD stabilises 1 against degradation in aqueous solutions.
Assuntos
Ciclodextrinas/química , Naftoquinonas/química , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Soluções Tampão , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Reprodutibilidade dos Testes , Soluções , Espectrofotometria Ultravioleta , TemperaturaRESUMO
The complexation of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I) with a highly soluble cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was studied in aqueous media by solubility methods. I is an antibacterial and trypanocidal agent that is undergoing preclinical testing. Unfortunately, I exhibits low water solubility, and it is therefore difficult to prepare the solutions for biological tests. I inclusion took place with 1:1 stoichiometry. The stability constants of the I complexes calculated from the slope and the intercept of the phase solubility diagrams are larger in the less ionized form, whereas greater overall solubility is obtained in basic media.