Synthesis and structure determination of new pharmaceutical cocrystals

[摘要] Pharmaceutical cocrystals have an important and influential role in the pharmaceutical industry through the formation of substitutional crystalline material to obtain the optimum physical properties of an active pharmaceutical ingredient (API) without changing its chemical properties. Pyrazinamide is anti-bacterial drug which is used to treat tuberculosis that infects the lung tissues. In this thesis, the ability of pyrazinamide to form co-crystals with different di-carboxylic acids through the formation of strong hydrogen bonds to form motifs is investigated. Pyrazinamide cocrystals were synthesised through different methods using a variety of different solvents and different starting stoichiometric ratios. New cocrystals were formed between pyrazinamide and glutaric acid (1:1), pyrazinamide and adipic acid (4:1), pyrazinamide and pimelic acid (1:1), and pyrazinamide and sebacic acid (2:1). In all cases, X-ray powder diffraction and NMR were used to characterise the new material formed with the crystal structures of these materials determined through single crystal X-ray diffraction. The crystal structure of a polymorph of azelaic acid was also determined through single crystal X-ray diffraction analysis following attempted synthesis of a pyrazinamide:azelaic acid cocrystal. Other new products were characterised through X-ray powder diffraction, although further structural analysis was not carried out. These include adducts based on pyrazinamide:oxalic acid, pyrazinamide:malonic acid, pyrazinamide:maleic acid, pyrazinamide:isonicotinamide, nicotinamide:isonicotinamide and isonicotinamide:fumaric acid. Attempts to prepare adducts between pyrazinamide with histidine and nicotinamide only resulted in a mixture, as did the combination of L-dopamaine with succinic acid.

[发布机构] University:University of Birmingham;Department:School of Chemistry

[关键词] Q Science;QD Chemistry