Abstract

The solubilities of the sodium salts of some sulfonamides, barbiturates and hydantoins have been determined in mixtures of propylene glycol and water. In many cases, the solubilities of the salts in the mixed solvents were lower than those in water, however, several compounds exhibited enhanced solubilities in the mixed solvents. This unexpected increase in solubility was not related to the lipophilicity of the acidic forms of the drugs and occurred in at least one member of each group of compounds. Analysis of the solid phase which had been equilibrated with each solvent indicated the formation of crystal hydrates for most of the solutes, and in at least one instance, mixed solvates. These compounds could be categorized on the basis of their desolvation temperatures. Those compounds with low temperatures of desolvation had increased solubilities in propylene glycol-water mixtures while compounds with high desolvation temperatures had decreased solubilities in the mixed solvents. These data indicate that crystal hydrate formation plays a significant role in determining if a cosolvent can be used to enhance the solubilities of certain sodium salts.

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