Rapid analysis of drug binding to β-cyclodextrin: part II substituents effect on physicochemical and co-conformational stability of drug/cyclodextrin complex

Abstract

In the pharmaceutical industry, the most common application of cyclodextrins (CyDs) is to enhance the solubility, stability, safety and bioavailability of drug molecules. Although, there have been many reports on the complexation of drugs with cyclodextrins, to date, CyDs interaction with drugs is not well understood. The purpose of this work is to show the successful applications of previous work employing a novel, versatile, compact, low-volume, routine apparatus, which consists of a pump, flask and a rotating cell holder for the simultaneous measurements of absorbance and circular dichroism (CD) that allows for the concurrent use of four different pathlengths for binding studies. To show the effect of substituents on drug/CyD binding, benzoic acid as an important precursor for the synthesis of many other organic substances and benzoic acid derivatives were used in this study. Also, an effective novel method for binding titration was employed. The pK_a, binding constants, stoichiometry and structural co-conformations of benzoic acid and derivatives/β-CyD complexes were elucidated and determined with accuracy. Substituents type and location show a significant effect on the extent of binding and physicochemical properties of the binding complex. The system proved efficiency, ability to be used routinely and the analysis time was reduced significantly to less than one fourth of the total analysis time used in conventional methods, with possible automation for high-throughput analysis.