Mechanism of polymorphism for pharmaceutical crystallization

• Main Author: Ching, Chi Bun
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Research Report
• Language: English
• Published: 2010
• Subjects: DRNTU::Science::Medicine::Pharmacy::Pharmaceutical technology
• Online Access: http://hdl.handle.net/10356/42259
• Institution: Nanyang Technological University

The objectives of this work are to investigate the mechanism and progression of polymorphic transformation and crystallization, study the effect of additives, solvents, and experimental conditions, and develop effective polymorph controlling strategy for pharmaceutical manufacture. The nucleation and transformation of two polymorphs of glycine (α- and γ-forms) have been investigated. The influence of additive, solvent and process parameters such as saturated temperature, seed size and stirring speed on the transformation behavior from metastable form to stable form were examined. The different polymorphs were unambiguously examined by using Powder XRD, Raman microscope, FTIR, TGA and DSC. The polymorphic transition temperature was determined by both DSC and solubility measurements. The in-situ Raman spectroscopy was used to monitor the polymorphic transformation process and the solid-phase polymorphic composition was quantitatively calculated using multivariate analysis. The polymorphic transformation in solvent was also in-situ inspected using microscope with heating/cooling stage. The integration of the different off-line and in-situ measurement and controlling techniques will be valuable in studying the crystallization and transformation mechanism of polymorphic systems and developing a robust crystallization process to obtain the desired polymorphic crystal products.