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Physical properties and crystallization of theophylline co-crystals
KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology, Transport Phenomena. (Transport Phenomena)
2010 (English)Licentiate thesis, monograph (Other academic)
Abstract [en]

This work focuses on the physical properties and crystallization of theophyline co-crystals. Co-crystals of theophylline with oxalic acid, glutaric acid and maleic acid have been investigated.

The DSC curves of these co-crystals show that their first endothermic peaks are all lower than the melting temperature of theophylline. The decomposition temperature of theophylline – oxalic acid co-crystal is at about 230 °C, determined by DSC together with TGA. After decomposition, the remaining theophylline melts at about 279 °C, which is higher than the known melting temperature of theophylline, suggesting a structure difference, ie. a new polymorph may have been formed. The formation of hydrogen bonds in theophylline – oxalic acid co-crystal was investigated by FTIR. Changes of FTIR peaks around 3120 cm-1 reflects the hydrogen bond of basic N of theophylline and hydroxyl H of oxalic acid. The solubility of theophylline – oxalic acid co-crystal and theophylline – glutaric acid co-crystal was determined in 4:1 chlroform – methanol and in pure chloroform respectively. At equilibrium with the solid theophylline – oxalic acid co-crystal, the theophylline concentration is only 60 % of the corresponding value for the pure solid theophylline. At equilibrium with the solid theophylline – glutaric acid co-crystal, the theophylline concentration is at least 5 times higher than the corresponding value for the pure solid theophylline. Two phases of theophylline were found during the solubility determination. In the chloroform – methanol mixture (4:1 in volume ratio) the solubility of the stable polymorph of theophylline is found to be about 14 % lower than that of the metastable phase. Various aspects of the phase diagram of theophylline – oxalic acid co-crystal was explored.

Theophylline – oxalic acid co-crystal has been successfully prepared via primary nucleation from a stoichiometric solution mixture of the two components in chloroform – methanol mixture. By slurry conversion crystallization, the co-crystal can be prepared in several solvents, and yield and productivity can be significantly increased. Theophylline – glutaric acid can be successfully prepared via both co-grinding of the two components and slow evaporation with seeding.

Place, publisher, year, edition, pages
Stockholm: KTH , 2010. , vi, 47 p.
Trita-CHE-Report, ISSN 1654-1081 ; 2010:26
Keyword [en]
Theophylline, oxalic acid, glutaric acid, maleic acid, co-crystal, decomposition temperature, melting temperature, solubility, crystallization
National Category
Chemical Process Engineering
URN: urn:nbn:se:kth:diva-13255ISBN: 978-91-7415-689-8OAI: diva2:322893
2010-06-15, D41, Lindstedtsvägen 17, KTH, Stockholm, 16:24 (English)
QC20100608Available from: 2010-06-09 Created: 2010-06-08 Last updated: 2010-06-09Bibliographically approved

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