Determination of binding affinity for chenodeoxycholate in equilibrium with sulfobutylether-β-cyclodextrin

J Pharm Sci. 2012 Aug;101(8):2883-90. doi: 10.1002/jps.23231. Epub 2012 Jun 6.

Abstract

A kinetic dialysis technique together with a radiolabeled chenodeoxycholate (CDC) was used to determine the existence of a relationship between the monomer concentration of CDC and the total CDC concentration in different CDC solutions containing 1 or 5 mM sulfobutylether (SBE)-β-cyclodextrin. On the basis of the nature of the relationship and a binding model with binding constants of K₁ and K₂, the binding affinity for the solutions was quantified at the best curve fitting using a least-squares technique. The very high binding affinity of K₁ and the very low (i.e., negligible) binding affinity of K₂ indicate the formation of 1:1 inclusion complexes. In addition, the values of K₁ and K₂ were reasonably interpreted. Similar analysis showed that the formation of 1:2 inclusion complexes and the self-association of the SBE-β-cyclodextrin molecules in the solutions are unlikely. The present study provides a basis for investigating the self-association, quantifying the binding affinity, and interpreting the quantified values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chenodeoxycholic Acid / chemistry*
  • Dimerization
  • Kinetics
  • Least-Squares Analysis
  • Models, Chemical
  • Pharmaceutical Vehicles / chemistry*
  • beta-Cyclodextrins / chemistry*

Substances

  • Pharmaceutical Vehicles
  • beta-Cyclodextrins
  • Chenodeoxycholic Acid
  • SBE4-beta-cyclodextrin