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Stoichiometric control of co-crystal formation by solvent free continuous co-crystallization (SFCC).
Kulkarni, Chaitrali S. Wood, Clive Kelly, Adrian L. Blagden, Nicholas
Kulkarni, Chaitrali S.
Wood, Clive
Kelly, Adrian L.
Blagden, Nicholas
Publication Date
2015
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© 2016 ACS. Reproduced in accordance with the publisher's self-archiving policy. This document is the author's version of a Submitted Work that was accepted for publication in Crystal Growth & Design. Copyright © American Chemical Society after peer review. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.5b00806
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openAccess
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2015-10-29
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Abstract
Reproducible control of stoichiometry and difficulties in large scale production have been identified as two of the major challenges to commercial uptake of pharmaceutical co-crystals. The aim of this research was to extend the application of SFCC to control stoichiometry in caffeine: maleic acid co-crystals. Both 1:1 and 2:1 caffeine: maleic acid co-crystals were produced by control of the feedstock composition and process conditions. It was also observed that formation of 2:1 stoichiometry co-crystals involved formation of a 1:1 co-crystal which was subsequently transformed to 2:1 co-crystals. The investigation of stoichiometric transformation revealed that although 1:1 co-crystals could be converted into 2:1 form with addition of excess caffeine, the reverse was not possible in the presence of excess maleic acid. However, conversion from 2:1 into 1:1 was only achieved by melt seeding with the phase pure 1:1 co-crystals. This investigation demonstrates that stoichiometric control can be achieved by SFCC by control of parameters such as extrusion temperature.
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Accepted manuscript
Citation
Kulkarni C, Wood C, Kelly AL et al (2015) Stoichiometric control of co-crystal formation by solvent free continuous co-crystallization (SFCC). Crystal Growth & Design. 15(12): 5648–5651.
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Article