Rubino J T
School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
J Pharm Sci. 1989 Jun;78(6):485-9. doi: 10.1002/jps.2600780614.
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.
测定了多种弱酸性药物钠盐在水中的溶解度。所检测的化合物包括巴比妥酸盐、磺胺类药物和乙内酰脲类。当将这些盐的水溶性对数与其熔点作图时，观察到一种反比关系；然而，良好的相关性并非立竿见影。使用量热法、分光光度法和重量法，对药物与水达到平衡后的固相进行了进一步研究。在许多情况下，水合物的形成很明显，并且对于某些化合物，与水达到平衡前后，晶体中化学计量的水量有所不同。对数据的多变量分析表明，摩尔溶解度的对数与熔点和晶体水合物中化学计量的水量均呈反比关系，但与药物相应酸形式的极性无关。因此，对于这些药物的钠盐，溶解度主要由与溶液相处于平衡状态的固相性质控制。
