Improvement of water solubility of sulfamethizole through its complexation with ß- and hydroxypropyl-ß-cyclodextrin - Characterization of the interaction in solution and in solid state

Abstract

The aim of this study was to increase the solubility of sulfamethizole in water by complexing it with b-cyclodextrin (BCD) and hydroxypropyl-b-cyclodextrin (HPBCD). The interaction of sulfamethizole with the cyclodextrins was evaluated by the solubility, H NMR spectrometry and molecular modelling. The stability constants calculated from the phase solubility method increase in order HPBCD,BCD. From the NMR studies could be concluded that the sulfamethizole:cyclodextrin mole ratio was 1:1 (mol/mol) in the BCD complex and 2:3 (mol/mol) in the HPBCD complex. In both cases the sulfamethizole moiety included in the cyclodextrin was the thiadiazole group. MM2 calculations, either in vacuum or in the presence of a solvent, support this structure. Solid inclusion complexes of sulfamethizole with BCD and HPBCD were obtained by freeze drying 1:1 (mol/mol) solutions in aqueous ammonium hydroxide. Host–guest interactions were studied in the solid state by powder X-ray diffractometry and differential scanning calorimetry. The dissolution rates of sulfamethizole increased by the complexation with BCD or HPBCD