MULTIPLE COMPLEX-FORMATION OF UNSTABLE COMPOUNDS WITH CYCLODEXTRINS -EFFICIENT DETERMINATION AND EVALUATION OF THE BINDING CONSTANT WITH IMPROVED KINETIC-STUDIES

Equations were derived that allow the determination of cyclodextrin-co mpound complex primary and secondary binding constants by using kineti c analysis (by monitoring the degradation rate constant of the compoun d in the presence of cyclodextrins). The degradation rate constant is dependent on the concentration of cyclodextrins in the solution of the compound and also on the stoichiometry of the cyclodextrin-compound c omplex. It was found that riboflavin (a photosensitive compound) forms a 1:2 inclusion complex with alpha-cyclodextrin and a 1:1 complex wit h gamma-cyclodextrin. Indomethacin (sensitive to hydrolysis) also form s a 1:1 complex with beta-cyclodextrin. Both compounds are unstable an d can be stabilized through complexation with cyclodextrins. The bindi ng constants were also calculated fluorimetrically for riboflavin and by H-1 NMR spectrometry for indomethacin in order to compare the value s from the different methods. The fact that the same compound (ribofla vin) can exhibit different binding behaviors with different cyclodextr ins could result in new descriptive studies for each particular case.