Development of a Small-Scale Automated Solubility Measurement Apparatus

A semiautomated device for solubility measurements in solution volumes as low as 1 mL was developed for pharmaceutical applications. The device operates nonisothermally, and can measure multiple samples simultaneously. Solubilities of model compounds such as paracetamol, mannitol, adipic acid, and glycine were measured and showed a maximum deviation of 5 wt % compared to literature data. Extrapolation of solubility data in the form of activity coefficients was found in good agreement with the literature value over a wide range of temperatures for paracetamol in 2-propanol and adipic acid in ethanol, while some deviation was observed for mannitol in water. The use of the solubility-measuring device to perform solvent screening on multiple solvents for early-stage pharmaceutical compounds was also examined. Results indicate that the slope of the solubility curve with temperature can be estimated with limited data for multiple solvents.