Multicomponent crystals of Nitrofurazone

• Main Author: Sharara, Kudzaishe Nigel
• Other Authors: Báthori, Nikoletta B., Prof
• Language: en
• Published: Cape Peninsula University of Technology 2019
• Subjects: Nitrofurans; Crystallography; Pharmaceutical chemistry; Hydrogen bonding
• Online Access: http://hdl.handle.net/20.500.11838/2780

Thesis (Master of Applied Science in Chemistry)--Cape Peninsula University of Technology, 2018. === Physicochemical property enhancement of drugs is one of the focus areas of the pharmaceutical industry. This research demonstrates how crystal engineering methods offer a practical way to make systematic solid state modifications of active pharmaceutical ingredients. Nitrofurazone ((5-nitro-2-furaldehydesemicarbazone), NFZ) was selected for multicomponent crystal formation, in order to improve its aqueous solubility without modification of its molecular structure. NFZ has both hydrogen bond donor and hydrogen bond acceptor groups on its semicarbazone chain; therefore, it seemed to be a suitable target to use synthon engineering principles to form a series of multicomponent crystals. Also, the torsional flexibility of the NFZ molecule suggested great adaptability of the molecule and thus good potential for forming a variety of crystalline solids with the selected co-formers. Surprisingly, 95% of the time the co-crystallisation experiments failed and the ,  or polymorph of NFZ were obtained. The polymorph of NFZ was known since 1994. Parallel to this work, room temperature crystal structures of the and -polymorphs were reported by an independent research group. Although the crystal structures presented in this thesis were collected at 173 K, they are essentially the same as the already published ones with the obvious difference between the atomic thermal ellipsoids. Multicomponent crystals of NFZ were formed only when the API was exposed to perchloric acid (HClO4), phosphoric acid (H3PO4) and propionic acid (PA). These crystallisations resulted in the formation of 4NFZ•[H3O+][ClO4-], NFZ•H3PO4 and NFZ•PA crystals, respectively. The crystal structures were analysed with single crystal X-ray diffraction and the bulk properties of the material were analysed using powder X-ray diffraction, thermo-analytical methods and Fourier transform infrared spectroscopy. The most significant observation of the project was the extreme difficulty of the multicomponent crystal formation of NFZ, even though the API has great hydrogen bonding capabilities associated with torsional flexibility. To understand this behaviour, the solid state behaviour of the semicarbazone moiety was analysed with the aid of data retrieved from the Cambridge Structural Database. The torsional flexibility of the semicarbazone moiety was also investigated and the most common conformers were identified; and these results were supported by the findings of computational methods.