Interaction of povidone with aromatic compounds I: Evaluation of complex formation by factorial analysis.

In a study of complex formation between macromolecules and small ligands such as drugs, it appeared that the association constants must be calculated with more care (i.e., after a thorough investigation of the influencing parameters such as buffer composition, ionic strength, and temperature) to allow meaningful interpretations of the phenomena. For this purpose, factorial analysis seems to be the method of choice; it offers the advantage of evaluating the influence of several variables and their interactions at the same time with a minimum of experiments. The method was applied to the association of povidone with two ligands, salicylic acid and benzoic acid. Parameters such as buffer composition and ionic strength, which affect binding, could be distinguished. Especially at pH 7.00, a great positive influence of buffer ions (phosphate buffer) and a relative positive interaction between temperature and ionic strength were noted. Knowledge of the influences of these parameters allowed comparison of the effects of the functional groups attached to the ligand molecules, as well as their degree of dissociation, on adsorption to permit more meaningful interpretation of thermodynamic constants.