MEASUREMENT OF MOLECULAR ASSOCIATION IN DRUG-CYCLODEXTRIN INCLUSION COMPLEXES WITH IMPROVED H-1-NMR STUDIES

The molecular association of haloperidol with hydroxypropyl-B-cyclodex trin, expressed by the binding constant of the inclusion complex forme d, was calculated from the changes on the H-1 NMR spectra of the drug in the presence of the cyclodextrin. The stoichiometry of the complex was calculated by use of the continuous variation method (Job plot), a nd found to be 1:1. The binding constant for the 1:1 complex was calcu lated using improved non-linear models, which were solved by non-linea r least-squares regression analysis, applying an iteration procedure.T hree improved mathematical models for more accurate calculation of bin ding constants are proposed. The models are free from any assumptions and from practical or theoretical shortcomings.