Some Physical Factors Affecting the Enhanced Blepharoptotic Activity of Orally Administered Reserpine-Cholanic Acid Coprecipitates

In order to elucidate the mechanism by which orally administered cholanic acid derivative-reserpine coprecipitates potentiate the pharmacological activity of reserpine in mice, a study of the surface tension and dissolution properties of the various systems was undertaken. Deoxycholic acid, cholic acid, lithocholic acid, and 3,12,24-trihydroxycholane were found to significantly lower surface tension. These same compounds, as coprecipitates, enhanced the ptotic activity of reserpine. A fifth compound, 5β-cholanic acid, showed only minor surface tension lowering properties. No indication of micelle formation was observed with these five compounds in the pH 6.4 buffer system used. In vitro dissolution studies of the coprecipitates of reserpine with these compounds in ethyl acetate at 37° were also undertaken. An increase in the dissolution rate of the coprecipitates over that for pure reserpine was noted, due most probably to a reduction in the particle size of reserpine during the formation of the coprecipitates. The rate of dissolution of reserpine from the coprecipitates in a 1:16 molar ratio showed a rank order correlation with in vivo potency.