Dissolution Rates of High Energy Polyvinylpyrrolidone (PVP)-Sulfathiazole Coprecipitates

Abstract

The apparent solubility and rate of solution of sulfathiazole from compressed tablets containing polyvinylpyrrolidone (PVP) were found to be greatly increased if sulfathiazole was previously coprecipitated with PVP. The increase noted was found to be function of the chain length of the PVP used as coprecipitate and the sulfathiazole to PVP weight ratio of the coprecipitate powder mixture used to compress the tablet. The 10,000-mol. wt. PVP yielded the most rapid sulfathiazole dissolution rate. The sulfathiazole rate of solution was (a) independent of the PVP weight fraction in the coprecipitated mixture at low PVP weight fractions; (b) increased with increasing PVP weight fraction at intermediate PVP weight fractions; and (c) decreased with increasing PVP weight fractions at high PVP weight fractions. A model was presented which utilized a controlling sulfathiazole external layer at lower PVP weight fractions and a controlling PVP external layer at higher PVP weight fractions. Several techniques were developed and used to elucidate the mechanisms involved and include (a) dissolution rate studies of mechanical mixes as well as coprecipitated mixtures of a number of sulfathiazole to PVP ratios; (b) X-ray diffraction studies of powders and tablets both before and after dissolution; (c) solubility determination of the various forms of sulfathiazole as a function of the PVP weight fraction in the coprecipitate and as a function of the PVP concentration in solution; (d) simultaneous release rates of PVP and sulfathiazole to determine regions of congruency and noncongruency; and (e) rates of solution using PVP solutions as a solvent. The data not only agreed very well with the model, but permitted a detailed characterization of all systems at all times during the dissolution process.