Study of the relation between the shape of lacosamide crystals and the composition of crystallization medium

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dc.contributor.advisor Fitzpatrick, John J. en Allegaert, Sven 2016-09-16T08:53:42Z 2016 2016
dc.identifier.citation Allegaert, S. 2016. Study of the relation between the shape of lacosamide crystals and the composition of crystallization medium. PhD Thesis, University College Cork. en
dc.description.abstract Crystallization is the critical process used by pharmaceutical industries to achieve the desired size, size distribution, shape and polymorphism of a product material. Control of these properties presents a major challenge since they influence considerably downstream processing factors. Experimental work aimed at finding ways to control the crystal shape of Lacosamide, an active pharmaceutical ingredient developed by UCB Pharma, during crystallization was carried out. It was found that the crystal lattice displayed a very strong unidirectional double hydrogen bonding, which was at the origin of the needle shape of the Lacosamide crystals. Two main strategies were followed to hinder the hydrogen bonding and compete with the addition of a Lacosamide molecule along the crystal length axis: changing the crystallization medium or weakening the hydrogen bonding. Various solvents were tested to check whether the solvent used to crystallize Lacosamide had an influence on the final crystal shape. Solvent molecules seemed to slow down the growth in the length axis by hindering the unidirectional hydrogen bonding of Lacosamide crystals, but not enough to promote the crystal growth in the width axis. Additives were also tested. Certain additives have shown to compete in a more efficient way than solvent molecules with the hydrogen bonding of Lacosamide. The additive effect has also shown to be compatible with the solvent effect. In parallel, hydrogen atoms in Lacosamide were changed into deuterium atoms in order to weaken the hydrogen bonds strength. Weakening the hydrogen bonds of Lacosamide allowed to let the crystal grow in the width axis. Deuteration was found to be combinable with solvent effect while being in competition with the additive effect. The Lacosamide molecule was eventually deemed an absolute needle by the terms of Lovette and Doherty. The results of this dissertation are aimed at contributing to this classification. en
dc.description.sponsorship European Commission (Marie Curie Fellowship) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2016, Sven Allegaert. en
dc.rights.uri en
dc.subject Lacosamide en
dc.subject Crystallization en
dc.subject Crystal shape en
dc.subject Solvent en
dc.subject Additive en
dc.subject Deuteration en
dc.title Study of the relation between the shape of lacosamide crystals and the composition of crystallization medium en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PHD (Engineering) en
dc.internal.availability Full text not available en Indefinite en 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder European Commission en
dc.description.status Not peer reviewed en Process & Chemical Engineering en
dc.check.reason Releasing this thesis would cause substantial prejudice to the commercial interests of the sponsor of the postgraduate research en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat Hard bound copy in Library only en
dc.internal.conferring Summer 2016 en

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© 2016, Sven Allegaert. Except where otherwise noted, this item's license is described as © 2016, Sven Allegaert.
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