TY - JOUR

T1 - Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether-ß-cyclodextrin

AU - Østergaard, Jesper

AU - Jensen, Henrik

AU - Holm, Rene

N1 - © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2012

Y1 - 2012

N2 - Sulfobutyl ether-ß-cyclodextrin (SBEßCD) is utilized in preformulation and drug formulation as an excipient for solubilization of drugs with poor aqueous solubility. Approximately seven negative charges of SBEßCD 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 SBEßCD 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 ß-cyclodextrins derivatives, i.e. the positions of the negative charges on SBEßCD and the bile salts within the complex did not lead to significant electrostatic repulsion.

AB - Sulfobutyl ether-ß-cyclodextrin (SBEßCD) is utilized in preformulation and drug formulation as an excipient for solubilization of drugs with poor aqueous solubility. Approximately seven negative charges of SBEßCD 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 SBEßCD 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 ß-cyclodextrins derivatives, i.e. the positions of the negative charges on SBEßCD and the bile salts within the complex did not lead to significant electrostatic repulsion.

U2 - 10.1002/jssc.201200502

DO - 10.1002/jssc.201200502

M3 - Journal article

C2 - 22997107

VL - 35

SP - 2764

EP - 2772

JO - HRC & CC, Journal of High Resolution Chromatography and Chromatography Communications

JF - HRC & CC, Journal of High Resolution Chromatography and Chromatography Communications

SN - 1615-9306

IS - 20

ER -