Study of structural features and thermodynamic parameters, determining the chromatographic behaviour of drug–cyclodextrin complexes

The chromatographic behaviour of host–guest inclusion complexes was studied, in order to predict the optimal conditions for their accurate analysis and overcome the significant analytical errors generated by the presence of cyclodextrins. Complexes of tolfenamic acid and ketoprofen with β-cyclodextrtin (βCD), 2-hydroxypropyl-βCD (HPβCD) and methyl-βCD (MeβCD) prepared in different molar ratios, were studied. Since the drug release from cyclodextrins’ complexes is a prerequisite for its accurate quantitation, several parameters affecting the dissociation during the analysis were evaluated. In an attempt to explain the drug release mechanism from cyclodextrins, during HPLC analysis, the possible correlation of the NMR structural findings with the binding constants and the thermodynamic quantities of complexation were examined, in relation to their chromatographic behaviour. Finally, the presence of the solvation spheres around the supramolecules, which affect the complex stability, is suggested to be crucial for our chromatographic findings. Particularly, entropy change in the system is considered the most critical factor, determining the time required for dissociation of drug–cyclodextrin complexes, during drug quantitation.