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.

Displacement of Drugs From Cyclodextrin Complexes by Bile Salts: A Suggestion of an Intestinal Drug-Solubilizing Capacity From an In Vitro Model

“…However, substitution not only increases the solubility, but also affects the ability of the cyclodextrin to form inclusion complexes. [12][13][14][15][16] The absorption of a cyclodextrin-complexed drug upon oral administration is a relatively complicated process, as outlined in Figure 1. The so-called "free fraction hypothesis" 1 dictates that only the free form of the drug, which is in equilibrium with the complexed species, is available for absorption.…”

“…[31][32][33] The equilibrium between cyclodextrins and bile salts and the micellization of bile salts have previously been investigated. [12][13][14][15][16][34][35][36] However, all experiments except one 35 have investigated one of these two reactions in isolation, thus not truly reflecting the physiological conditions. It is therefore unknown whether the dynamics in simultaneous presence of the two equilibria can be predicted by simple additivity from the parameter values known from the two individual equilibria.…”

“…These experiments were rationalized in terms of previous isothermal titration calorimetry (ITC) data on the two isolated reactions. That is the equilibrium between cyclodextrins and bile salts [12][13][14][15][16][34][35][36] and the stability of bile salts micelle. [37][38][39] On the basis of this knowledge, a model for the equilibrium system shown in Figure 1 was derived as a function of the drug amount absorbed.…”

Simultaneous quantification of the major bile acids in Artificial Calculus bovis by high-performance liquid chromatography with precolumn derivatization and its application in quality control

“…According to the correlative references, BAs are mainly quantified directly using LC–UV [, ], LC coupled with an evaporative light scattering detection (ELSD) , LC–MS , and CE . In addition, BAs can be determined using TLC scanning .…”

Affinity capillary electrophoresis to evaluate the complex formation between poliovirus and nanobodies

“…Several publications can be found describing the complex formation between small molecules (e.g. ). For large macromolecules, having an M r of 200.000 and more, affinity studies with CE are not abundantly described.…”