Sulfadiazine/hydroxypropyl-β-cyclodextrin host–guest system: Characterization, phase-solubility and molecular modeling

A 1:1 inclusion complex of sulfadiazine with hydroxypropyl β-cyclodextrin was prepared, characterized and modeled by RM1 and PM6 semiempirical methods. Phase-solubility and characterization of the system were carried out by standard methods. In this work we prepared and characterized an inclusion complex of the dihydropteroate synthase inhibitor sulfadiazine (SDZ) in 2-hydroxypropyl-β-cyclodextrin (HPBCD). From the phase-solubility diagram we observed an increase in the water solubility of the drug, calculating a binding constant of 1879 M −1. The inclusion mode involves a NH 2-in orientation of the drug in the HPBCD cavity, according to the 2D NMR (ROESY) data and confirmed by molecular modeling using the semiempirical PM6 and RM1 methods.