Solubilization by cosolvents III: diazepam and benzocaine in binary solvents

The solubilities of diazepam and benzocaine in various cosolvent-water mixtures have been measured and the ability of the log-linear solubility equation, log (S(m)/S_w) = σf, to predict the experimental solubilities examined. In general, the logarithmic increase in solubility (expressed as the ratio of the solubility in the solvent mixture, S(m), and water, S_w) with increasing volume fraction of cosolvent, f, was observed. Positive or negative deviation from the predicted linear behavior was observed for both solutes in all of the solvent systems studied. The magnitude of the slopes, σ of the log (S(m)/S_w) vs. f plots agreed with the order of the polarities of the cosolvents. These results are compared with those of a similar study involving the drug phenytoin. The slopes of the log (S(m)/S_w) vs. f plots were approximately in the same rank order for each cosolvent-water mixture. It was also observed that the patterns of curvature in the log (S(m)/S_w) vs. f plots for a given cosolvent-water system are similar for all three drugs. This suggests that the source of deviation of the observed solubility from the predicted solubility may primarily be due to interactions between the cosolvent and water.