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

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dc.check.date10000-01-01
dc.check.embargoformatHard bound copy in Library onlyen
dc.check.entireThesisEntire Thesis Restricted
dc.check.infoIndefiniteen
dc.check.opt-outYesen
dc.check.reasonReleasing this thesis would cause substantial prejudice to the commercial interests of the sponsor of the postgraduate researchen
dc.contributor.advisorFitzpatrick, John J.en
dc.contributor.authorAllegaert, Sven
dc.contributor.funderEuropean Commissionen
dc.date.accessioned2016-09-16T08:53:42Z
dc.date.issued2016
dc.date.submitted2016
dc.description.abstractCrystallization 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.sponsorshipEuropean Commission (Marie Curie Fellowship)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAllegaert, 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.identifier.urihttps://hdl.handle.net/10468/3092
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2016, Sven Allegaert.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectLacosamideen
dc.subjectCrystallizationen
dc.subjectCrystal shapeen
dc.subjectSolventen
dc.subjectAdditiveen
dc.subjectDeuterationen
dc.thesis.opt-outtrue
dc.titleStudy of the relation between the shape of lacosamide crystals and the composition of crystallization mediumen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePHD (Engineering)en
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