Chromatographic study of interactions between polyvinylpyrrolidone and drugs.

A chromatographic technique for the study of possible interactions of drugs with soluble or insoluble polymer additives is proposed. Crospovidone was used as a stationary phase. The method allowed the rapid determination of interaction constants in the range of greater than 1 M-1 as relevant for applications in practice. The interaction of 39 drugs and model compounds of diverse chemical structure with povidone and crospovidone was studied. The results closely agreed with data obtained from conventional equilibrium dialysis and sorption studies. The complexation reaction was found to be dominated by hydrogen binding. A close correspondence between the strength of interaction and the nature, number, and position of hydrogen-donating functional groups in the active ingredient was observed. The binding tendency was enhanced when the functional groups were connected with aromatic residues. The carboxyl group was more effective than the hydroxide or amino groups. The binding can be quantified by the binding constants, Kp and Ks, respectively, describing the interaction with polyvinylpyrrolidone via independent binding sites. At pH 1, with the exception of tannic acid, all investigated drugs exhibited Kp and/or Ks values well below an upper limit of 10 M-1. Hence, with additive-drug ratios commonly used in pharmaceutical preparations, the bound amount of drug after oral administration can hardly exceed 3%. In view of this already low degree of potential binding and considering its reversible character and its decreasing tendency with increasing pH during GI passage, the presence of polyvinylpyrrolidone in pharmaceutical preparations is not expected to interfere with GI drug absorption.