The determination of the amphiphilic properties of a prodrug (DDMS) of phenytoin in aqueous media

Abstract

During a previous study it was established that a change in the intrinsic solubility of phenytoin in the presence of its prodrug (DDMS), and a change in the rate of hydrolysis of the prodrug in the presence of higher concentrations thereof, could account for increases in precipitation times of aqueous prodrug solutions. The 50% reduction in the rate of hydrolysis observed at higher prodrug concentrations and the 45-fold increase in the solubility of phenytoin at therapeutic levels of the prodrug were both attributed to the observed increase in precipitation times. In an effort to explain the observed changes in solubility and kinetics a series of experiments were performed to determine the extent of the formation of amphiphilic structures in aqueous media. The presence of associative species in aqueous prodrug solutions was established by tensiometry, conductivity and dynamic light scattering experiments. Electron microscopy showed spherical shapes with sizes which compared favourably with the sizes found with the laser and Kratel particle counter techniques.