The interaction of 32 drugs of diverse chemical structure with cross-linked insoluble polyvinylpyrrolidone (crospovidone) was studied. By using a polymer to drug ratio of 10:1, the sorbed amount for 20 compounds was found to be less than 5%. After a 10-fold decrease of the polymer concentration, the sorbed amount of eight other compounds fell to or below the 5% level. Only tannic acid and hexylresorcinol exhibited a significantly stronger sorption tendency. The interaction appeared to be controlled by phenolic groups in the active ingredient. The binding can be quantified by an interaction constant Ks, whose definition is based on a bulk phase model of interaction via independent binding sites. The exceptionally strong binding of hexylresorcinol, however, apparently was caused by cooperative interacting of the hexyl groups in the bound state. Desorption studies revealed that the binding was fully reversible in all cases. Therefore, the presence of cross-linked polyvinylpyrrolidone as a disintegrant in pharmaceutical preparations is not expected to interfere with GI drug absorption.