pH-Solubility Profile of Papaverine Hydrochloride and Its Relationship to the Dissolution Rate of Sustained-Release Pellets

Abstract

The pH-solubility profile of papaverine hydrochloride (I) was determined using the phase-solubility technique and equilibrium solubilities in buffers. The release of I from sustained-release pellets consisting of a shellac-based matrix was determined by the USP basket technique and was found to exhibit zero-order kinetics. Release rates at various pH values of the permeating solvent were compared with the pH-solubility profile and were directly proportional to the solubility below, but not above, the apparent pHmax (3.9). This lack of proportionality was also shown by the intrinsic dissolution rates. The effect was attributed to the self-buffering action of I and the metastability of the papaverine salt-base system in the vicinity of pHmax. It is postulated that the outer layer of polymer and filler on the surface of the pellets forms a barrier which determines the rate of release. The inner matrix serves as a drug reservoir in which the internal pH may not be the same as the bulk pH.