title: Quercetin/beta-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture.
abstract: The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess amount of quercetin) on the complexation of quercetin with beta-cyclodextrin using a 2(3) factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37 degrees C/24 h/6 mM of quercetin. The stoichiometric ratio (1:1) and the apparent stability constant (Ks = 230 M(-1)) of the quercetin/beta-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production of a 1:1 quercetin/beta-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited to 4.6-fold in the presence of 15 mM of beta-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture of quercetin with beta-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold, similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio of 1:1, i.e., 6 mM of quercetin and 6 mM of beta-cyclodextrin).
authors.affiliation: Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Greice S
authors.initials: GS
authors.lastname: Borghetti
authors.forename: Ivana S
authors.initials: IS
authors.lastname: Lula
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Sinisterra
authors.forename: Valquiria L
authors.initials: VL
authors.lastname: Bassani
mesh_terms: D002152:Calorimetry, Differential Scanning; D003890:Desiccation; D004355:Drug Stability; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D011794:Quercetin / Q000737:chemistry*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D011794:Quercetin