Homogeneous nucleation induction time measurement and prediction of solubility and the relative stability of polymorphs

The purpose of this work is to investigate the nucleation behavior of glycine through measurements of nucleation induction time and to evaluate methods for the prediction of solubility of organic compounds as well as to determine if the computational methods employed can determine the stability of enantiotropic polymorphs and their transition temperature.;An electrodynamic levitation trap (ELT) was used to suspend a small charged droplet (25-50mum) without a container using an electric filed. This novel technique enables the measurement of the homogeneous nucleation induction time at high levels of supersaturation at almost identical conditions. The induction time data measured were fitted to Turnbull's model and an empirical model related to two-step nucleation. The nucleation rates of glycine from aqueous solution were calculated using these models. The results obtained showed that glycine does not fit the classical model of Turnbull and is fit well by the empirical model. While ammonium sulfate (an ionic material) is previous work was shown to fit Turnbull's model.;A Conductor-like screening model for real solvents (COSMO-RS), which is based on quantum chemical calculations and a statistical thermodynamic method, was used to calculate solubility and to determine the stability of polymorphs of drug compounds. The solubility results indicate that the COSMO-RS method is not superior to conventional group contribution methods. In addition, solubility calculations using molecules of interest did not correctly predict the solubility relationship between enantiotropic polymorphs. However, calculations using the unit cell of the compound showed some possibility of using this method for prediction of the relative stability of polymorphs.