Divalent cation binding specificities and microsphere formation of pyran copolymer and related polycarboxylates

Pyran copolymer is a polyanionic drug with a broad spectrum of biologic activities. The present study focuses on the physicochemical interactions of pyran with divalent cations. Potentiometric titration curves of pyran are typical of the general polyelectrolyte behavior of high charge density polycarboxylates and show no apparent conformational transitions. The interaction of pyran with divalent cations follows an order of affinity for site binding, Mn 2+ > Ca 2+ > Mg 2+, that is common also to four other polycarboxylates tested. The titration data indicate the formation of a soluble chelate complex, for which pyran, of the five polymers, shows the greatest propensity. Specific conditions in terms of pH and degree of neutralization are found under which complex formation is preceded by the precipitation of microspheres. However, only pyran and polyitaconic acid precipitate under conditions which are closest to physiologic. The experimental results suggest a mechanism for microsphere formation that is consistent with a hypothesized mechanism of pharmacologie action of pyran-divalent cation complexes.