Correlation of dielectric constant and solubilizing properties of tetramethyldicarboxamides

The dielectric constants of aqueous solutions of four tetramethyldicarboxamides (tetramethylpimelamide, tetramethylsuberamide, tetramethylazelamide, and tetramethylsebacamide) were measured at 25 degrees. The values obtained were utilized in assessing the solubility behavior patterns of glutethimide, a semipolar, water-insoluble drug in these amide-water systems. At equimolar concentrations of water-rich amide solutions, the solubilizing power paralleled the chain length of the amides. The higher homologs appeared to favor more extensive solvation, as shown by the lower dielectric constants of their resulting solutions. Deviation in solubilizing action between the odd-carbon amides and the even-carbon amides, however, was exhibited at higher amide concentrations. The two odd-carbon amides, tetramethylpimelamide and tetramethylazelamide, showed consistently greater solubilizing action. This phenomenon was attributed to the greater association tendencies of the odd-carbon amides with water, which effectively reduced self-associations of glutethimide.