A Study on the Metastable Zone Width and Induction Time in the Polymorphic Crystallization System

Metastable zone width (MSZW) is the region between the solubility and supersolubility. MSZW is usually determined by the polythermal method when the solution is continuously cooled at a constant cooling rate. Approximately half of the MSZW is considered as the optimal operating condition in industrial applications. Solute molecules in the supersaturated solution can aggregate and form clusters. When the size of a cluster exceeds a critical size, it becomes thermodynamically stable and the subsequent growth leads to a new crystal. The induction period is defined as the time interval between the creation of the supersaturation and the formation of critical nuclei. Both MSZW and induction time are important characteristic properties of crystallization for each solute-solvent system. Both MSZW and induction time can vary significantly among different solute-solvent systems and is also affected by the hydrodynamic and operating conditions of the studied system. However, the related studies in the literature are very few. In this three-year proposal, the MSZW and induction time among different solvent systems will be studied both experimentally and theoretically. L-glutamic acid nucleates as two polymorphs- α form (prismatic) and β form (needlelike). As different polymorphs of the same substance can have different properties, such as solubility and bioactivity, L-glutamic acid is used as a model compound to study the effects of MSZW and induction time on the polymorph among different solvent systems. In the first year, a batch experimental set-up is designed to study the effects of temperature, supersaturation, stirring rate and different solvent on the MSZW of the two polymorphs. The resulting polymorphic powder composition is analyzed by X-ray diffraction (XRD) and Raman spectroscopy. We will develop a model based on progressive nucleation to interpret the MSZW by the polythermal method using the classical nucleation theory. The new model will relate the interfacial energy of the compound to the MSZW. The experimental MSZW data obtained is compared with the model. Besides, the experimental MSZW data in the literature is also compared to verify the model. In the second year, a batch experimental set-up is designed to study the effects of temperature, supersaturation, stirring rate and different solvent on the induction time of the two polymorphs. The resulting polymorphic powder composition is analyzed by XRD and Raman spectroscopy. The model developed in the first year is applied to relate MSZW with the induction time. The experimental induction time data obtained is compared with the model. Besides, the experimental induction time data in the literature is also compared to verify the model. In the third year, the effects of various impurities and ultrasound on the MSZW and induction time among different solvents are investigated. The resulting polymorphic powder composition is analyzed by XRD and Raman spectroscopy. The developed model is modified to interpret the effects of various impurities and ultrasound on the MSZW and induction time. The experimental MSZW and induction time data is compared with the model. Besides, the experimental MSZW and induction time data in the literature is also compared to verify the model.

Project ID:PB10501-2698
External Project ID:MOST103-2221-E182-067-MY3