Anderson B D, Conradi R A
J Pharm Sci. 1985 Aug;74(8):815-20. doi: 10.1002/jps.2600740803.
A number of metal and amine salts of the nonsteroidal anti-inflammatory drug 2-(2-fluoro-4-biphenylyl)propionic acid (flurbiprofen) (1) were synthesized, and the water solubilities of these materials were investigated. The solubility of flurbiprofen versus pH is in excellent agreement with the theoretical profile which assumes an intrinsic solubility of 5.0 X 10(-5) M for the free acid and a pKa of 4.22. The solubility determination of 1:1 amine salts of slightly soluble carboxylic acids is complicated by possible precipitation of the free acid when the salt is dissolved in water. The lower than expected apparent salt solubility seen when this phenomenon occurs is referred to as the "stoichiometric solubility." A theoretical treatment delineating three distinct regions in the phase solubility diagram for the tromethamine salt of flurbiprofen illustrates the care which must be taken in characterizing the system for salt solubility determinations. A multiple linear regression analysis was carried out to determine the relationship between the log Ksp of six amine salts and their melting points and cation hydrophilicities. While a strong dependence of Ksp on melting point was found, there was not a significant correlation between Ksp and amine cation hydrophilicity.
合成了非甾体抗炎药2-(2-氟-4-联苯基)丙酸（氟比洛芬）(1)的多种金属盐和胺盐，并研究了这些物质的水溶性。氟比洛芬的溶解度与pH值的关系与理论曲线非常吻合，该理论曲线假定游离酸的固有溶解度为5.0×10⁻⁵ M，pKa为4.22。当微溶性羧酸的1:1胺盐溶解于水时，游离酸可能沉淀，这使得其溶解度测定变得复杂。当出现这种现象时，观察到的表观盐溶解度低于预期，这被称为“化学计量溶解度”。对氟比洛芬的 tromethamine 盐在相溶解度图中三个不同区域的理论处理表明，在表征盐溶解度测定系统时必须谨慎。进行了多元线性回归分析，以确定六种胺盐的log Ksp与其熔点和阳离子亲水性之间的关系。虽然发现Ksp强烈依赖于熔点，但Ksp与胺阳离子亲水性之间没有显著相关性。
