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This thesis investigates a range of experimental and computational approaches for the discovery of solid forms. Furthermore, we gain, as readers, a better understanding of the key factors underpinning solid-structure and diversity. A major part of this thesis highlights experimental work carried out on two structurally very similar compounds. Another important section involves looking at the influence of small changes in structure and substituents on solid-structure and diversity using computational tools including crystal structure prediction, PIXEL calculations, Xpac, Mercury and statistical modeling tools. In addition, the author presents a fast validated method for solid-state form screening using Raman microscopy on multi-well plates to explore the experimental crystallization space. This thesis illustrates an inexpensive, practical and accurate way to predict the crystallizability of organic compounds based on molecular structure alone, and additionally highlights the molecular factors that inhibit or promote crystallization.
List of contents
Introduction.- Aims and Objectives.- Materials and Methods.- Development and Validation of High_Throughput Crystallization and Analysis (HTCAA) Methodology for Physical Form Screening.- Predicting Crystallizability of Organic Molecules using Statistical Modelling Techniques.- Exploring Crystal Structure Landscape of Olanzapine.- Exploring the Physical Form Landscape of Clozapine, Amoxapine and Loxapine.- Conclusions and Further Work.
Summary
This thesis investigates a range of experimental and computational approaches for the discovery of solid forms. Furthermore, we gain, as readers, a better understanding of the key factors underpinning solid-structure and diversity. A major part of this thesis highlights experimental work carried out on two structurally very similar compounds. Another important section involves looking at the influence of small changes in structure and substituents on solid-structure and diversity using computational tools including crystal structure prediction, PIXEL calculations, Xpac, Mercury and statistical modeling tools. In addition, the author presents a fast validated method for solid-state form screening using Raman microscopy on multi-well plates to explore the experimental crystallization space. This thesis illustrates an inexpensive, practical and accurate way to predict the crystallizability of organic compounds based on molecular structure alone, and additionally highlights the molecular factors that inhibit or promote crystallization.
