In-Situ studies of crystallization processes and other aspects of polymorphism

The work presented in this thesis represents the study of the polymorphism exhibited by several molecular, organic solid-state systems. In-situ techniques are used to explore aspects of the polymorphism and crystallization behaviour displayed by these systems. The crystal structures of new polymorphs and other solid phases are determined directly from powder X-ray diffraction data. Chapter 1 provides background information on the phenomenon of polymorphism and the importance of its study. In addition, the range of in-situ techniques that have been used to study crystallization and solid-state systems is described. Chapter 2 gives details on the experimental techniques used in the work presented in this thesis. These include powder X-ray diffraction (including the methodology behind structure determination from powder X-ray diffraction data), solid-state nuclear magnetic resonance (NMR) spectroscopy, X-ray photoelectron spectroscopy, thermal analysis techniques and dynamic vapour sorption. Chapter 3 explores the polymorphism of m-aminobenzoic acid, resulting in the discovery and characterization of three new polymorphs. The crystallization of m-aminobenzoic acid from solution is studied via in-situ solid-state NMR spectroscopy and this in-situ technique is expanded to allow the evolution of both the solid and liquid phases during the crystallization process to be studied. Chapter 4 investigates the crystallization behaviour of triphenylphosphine oxide and methyldiphenylphosphine oxide from solution using in-situ solid-state NMR spectroscopy. Evidence is found for transient, unknown solid phases formed during the crystallization process. Chapter 5 reports new insights into the crystallization behaviour of polymorph II of the drug rac-ibuprofen. Differential scanning calorimetry and in-situ powder X-ray diffraction experiments demonstrate that previous assumptions about the crystallization behaviour of this polymorph were incorrect. Finally, Chapter 6 explores the crystalline phases of the amino acid L-phenylalanine. A new polymorph and two hydrate phases are discovered and their hydration/dehydration behaviour