Solubilities and solid state properties of the sodium salts of drugs

The solubilities in water of a number of sodium salts of weakly acidic drugs were determined. The compounds examined included barbiturates, sulfonamides, and hydantoins. When the logarithm of the aqueous solubilities of the salts were plotted against their melting points, an inverse relationship was observed; however, a good correlation was not immediately apparent. Further studies were conducted on the solid phases of the drugs after equilibration with water, using calorimetric, spectrophotometric, and gravimetric methods. In many cases, hydrate formation was evident and, for some compounds, the stoichiometric amount of water in the crystal was different before and after equilibration with water. Multivariate analysis of the data indicated that the logarithms of the molar solubilities were inversely related to both the melting points and the stoichiometric amounts of water in the crystal hydrates, but were unrelated to the polarity of the corresponding acid forms of the drugs. Therefore, for the sodium salts of these drugs, the solubility is primarily controlled by the properties of the solid phase which exists in equilibrium with the solution phase.