title: Improvement of water solubility of sulfamethizole through its complexation with beta- and hydroxypropyl-beta-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 beta-cyclodextrin (BCD) and hydroxypropyl-beta-cyclodextrin (HPBCD). The interaction of sulfamethizole with the cyclodextrins was evaluated by the solubility, 1H 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.
authors.affiliation: Departamento de Farmacia e Tecnoloxía Farmacéutica, Fac. de Farmacia, Univ. de Santiago de Compostela, Campus Sur, E-15782 Santiago de Compostela, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Pose-Vilarnovo
authors.forename: I
authors.initials: I
authors.lastname: Perdomo-López
authors.forename: M
authors.initials: M
authors.lastname: Echezarreta-López
authors.forename: P
authors.initials: P
authors.lastname: Schroth-Pardo
authors.forename: E
authors.initials: E
authors.lastname: Estrada
authors.forename: J J
authors.initials: JJ
authors.lastname: Torres-Labandeira
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients; D005612:Freeze Drying; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D012995:Solubility; D012996:Solutions; D013419:Sulfamethizole / Q000737:chemistry*; D014867:Water; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D013419:Sulfamethizole; C031215:betadex