Pharmaceutical cocrystals : a contribution to fundamental studies addressing solubility, dissolution, formation and characterisation

Abstract

This thesis has focused on the study of pharmaceutical cocrystals. The investigations have addressed the solubility, dissolution and stability of cocrystals as well as the evaluation of selected production techniques, in order to contribute to an overall understanding of these solid state forms. Extensive evaluation of known cocrystals such as the benzamideidibenzyl sulfoxide cocrystal and three sulfadimidine:aromatic carboxylic acid (benzoic acid, salicylic acid, 4-aminosalicylic acid) cocrystals as well as newly synthesised cocrystals are presented in this work. Nicotinic acid and pyrazine-2-carboxylic acid have been introduced as potential new cocrystal formers with sulfadimidine. Several techniques such as X-ray diffraction, thermal analyses, infra-red spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis, high performance liquid chromatography, dynamic vapour sorption analysis and appropriate statistical tests have been used for analysing the properties of cocrystal studied and interpreting the results.