Solubility Measurement Using Differential Scanning Calorimetry

The measurement of solubility in microsamples employing a differential scanning calorimeter (DSC) has been evaluated for several aqueous and nonaqueous systems: substance A in acetonitrile, (RS)-mandelic acid, (S)-mandelic acid, adipic acid, diphenhydramine HCl, α-glycine, and terephthalic acid in water, (RS)-mandelic acid and β-succinic acid in ethanol and methanol, and adipic acid in ethanol. This technique requires samples in the range of milligrams and can be used at high temperatures and pressures. Results show that the solubility data of most compounds studied using this technique are within 5% of solubility data obtained from the literature. Factors that influence solubility measurement by DSC were examined along with methods to minimize associated errors.