Elliot I. Stupak

Biopharmaceutical and physicochemicai studies on reserpine-polyvinylpyrrolidone coprecipitates

The effect of varying the composition of drug- polyvinylpyrrolidone coprecipitates on the oral absorption characteristics of reserpine was assessed in the rat by urinary excretion studies. Both the rate and extent of absorption of reserpine from either a 1∶2,1∶5,or 1∶10 (w/w)ratio reserpinepolyvinylpyrrolidone coprecipitate were increased two- to threefold. This finding indicates that at coprecipitate ratios of 0.5or less, the enhanced absorption of reserpine is apparently independent of polyvinylpyrrolidone content. The in vitrodissolution rates of these test systems at 37°Ccorrelated very well with the in vivoabsorption data, suggesting dissolution rate- limited absorption, The results of physicochemical studies suggest that on coprecipitation of reserpine with polyvinylpyrrolidone a highly energetic form of the drug, most probably amorphous in nature, is formed. The solubility characteristics of this high- energy crystal form, as compared to those of the most thermodynamically stable form of the drug, appear to be responsible for the marked enhancement noted in both the dissolution and the absorption of reserpine from polyvinylpyrrolidone coprecipitates.