Towards an understanding of mechanically activated solid state phase transformations in small molecular organic crystals

The objective of this project was to investigate mechanically activated solid state phase transformations in pharmaceutically relevant small molecular organic crystalline materials. The central hypothesis tested here is that elements of the crystallographic structure of certain molecular crystalline materials predispose them to mechanical activation. The work described herein is divided into two main sections. In the first, crystal-crystal transformations are investigated using chlorpropamide as a model compound. Its A and C polymorphs, known to undergo a compaction facilitated phase interconversion, were studied to find a structural and phenomenological explanation for its unique transition behavior. For both materials, the extent of transformation as a result of compression was found to increase with applied pressure up to a maximum, which corresponded directly with the point of maximum densification. Physical experimentation also showed that the application of shear stresses is essential for the facilitation of both chlorpropamide transitions. A comparison of the crystal structures indicated significant similarities between the two; though sufficient to allow a shear-based diffusionless phase transformation. The second section of this work details the adaptation and development of a model for the prediction of mechanical disordering potential based on the physical and mechanical properties of a small molecular organic material, and considers the changes in free energy needed to incorporate a critical number of dislocations in a crystal lattice. The model was tested on seven model compounds using a cryogenic mill, six of which behaved as predicted by the model