General trends in the desolvation behavior of calcium salts and the characterization of mesomorphous calcium salts

The general objective of this project is to characterize, investigate and understand the physical and chemical properties of liquid crystals obtained from hydrated calcium salts upon dehydration. This work will also test the hypothesis that mesomorphous calcium salts are liquid crystals with intermediate physical and chemical properties between the corresponding crystalline and amorphous phases. The work described in this thesis is divided into two major parts. The first section details the general trends in the dehydration behavior of calcium salts of pharmaceutical carboxylic acids. Several calcium salts were synthesized and their crystal structures were solved. The crystal packing, the flexibility of the studied molecules and water channels in the crystal structures were identified as major factors in determining whether or not the calcium salt will become a liquid crystal upon dehydration. Besides, the solubilities of crystalline and liquid crystalline calcium ketoprofen, fenoprofen calcium and calcium salicylate were measured and the solubilities of the liquid crystalline phases were higher in all three cases. Variable temperature solid-state NMR was also used to investigate the mobility of amorphous and liquid crystalline calcium ketoprofen. In the second part the Pair Distribution Function (PDF) method, used to analyze three model liquid crystalline compounds, was described and validated. This method enabled us to study the molecular structure of the partially disordered model compounds