title: Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether-β-cyclodextrin.
abstract: Sulfobutyl ether-β-cyclodextrin (SBEβCD) is utilized in preformulation and drug formulation as an excipient for solubilization of drugs with poor aqueous solubility. Approximately seven negative charges of SBEβCD play a role with respect to solubilization and complexation, but also have an influence on the ionic strength of the background electrolyte when the cyclodextrin is used in capillary electrophoresis. Mobility-shift affinity capillary methods for investigation of the complexation of taurocholate and taurochenodeoxycholate with the negatively charged cyclodextrin derivative applying constant power and ionic strength conditions as well as constant voltage and varying ionic strength were investigated. A new approach for the correction of background electrolyte ionic strength was developed. Mobility-shift affinity capillary electrophoresis experiments obtained at constant voltage and constant power settings were compared and found to provide binding parameters that were in good agreement upon correction. The complexation of taurochenodeoxycholate with SBEβCD was significantly stronger than the corresponding interaction involving taurocholate. The obtained stability constants for the bile salts were in the same range as those previously reported for the interaction with neutral β-cyclodextrins derivatives, i.e. the positions of the negative charges on SBEβCD and the bile salts within the complex did not lead to significant electrostatic repulsion.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. joe@farma.ku.dk
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.forename: René
authors.initials: R
authors.lastname: Holm
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D007700:Kinetics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D001647:Bile Acids and Salts; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin