Optimised crystal morphologies for active pharmaceutical ingredients and related studies

dc.check.date10000-01-01
dc.check.embargoformatE-thesis on CORA onlyen
dc.check.entireThesisEntire Thesis Restricted
dc.check.infoIndefiniteen
dc.check.opt-outYesen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorMoynihan, Humphrey A.en
dc.contributor.authorHorgan, Danielle E.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderClarochem Ireland Ltd.en
dc.date.accessioned2015-11-18T12:15:50Z
dc.date.issued2015
dc.date.submitted2015
dc.description.abstractThe majority of active pharmaceutical ingredients (APIs) are crystalline solids in their pure forms. Crystalline solids have definable morphologies, i.e. shape and size. Crystal morphology is determined by both the internal structure of the crystals and external factors during growth from solution. The morphology of a crystal batch can affect key processes during manufacturing. Companies generally accept whatever morphology the manufacturing process provides and deal with any subsequent problems by costly trouble‒shooting. Rational design of optimised morphologies for crystalline pharmaceutical solids would be a very significant technical and commercial advance. Chapter one introduces the concept of crystal nucleation and growth. The phenomenon of polymorphism alongside the causes and impact is discussed. A summary of the scope of instrumentation used in the investigation of crystal polymorphism and morphology, including crystal size distribution (CSD), is also included. Chapter two examines the research carried out during an exploration of the optimum crystallisation parameters of phenacetin. Following a morphological study, the impact this induces on particle density and flow properties is examined. The impact of impurities on the crystallisation properties of phenacetin is investigated. Significantly, the location of impurities within individual crystals is also studied. The third chapter describes an industrial collaboration looking at the resolution and polymorphic study of trometamol and lysine salts of ketoprofen and 2‒phenylpropionic acid (2‒PPA). Chapter four incorporates a solid state study on three separate compounds: 2‒chloro‒4‒nitroaniline, 4‒hydroxy‒N‒phenylbenzenesulfonamide and N‒acetyl‒D‒glucosamine‒6‒O‒sulfate. 2‒Chloro‒4‒nitroaniline and 4‒hydroxy‒N‒phenylbenzenesulfonamide both produced interesting, extreme morphologies which warranted further investigation as part of a collaborative study. Following a summarisation of results in chapter five, chapter six contains the full experimental details, incorporating spectral and other analytical data for all compounds synthesised during the course of the research.en
dc.description.sponsorshipIrish Research Council (Enterprise Partnership Scheme (EPS))en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHorgan, D. E. 2015. Optimised crystal morphologies for active pharmaceutical ingredients and related studies. PhD Thesis, University College Cork.en
dc.identifier.urihttps://hdl.handle.net/10468/2072
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2015, Danielle E. Horgan.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectOrganic chemistryen
dc.subjectCrystallisationen
dc.subjectCrystal engineeringen
dc.thesis.opt-outtrue
dc.titleOptimised crystal morphologies for active pharmaceutical ingredients and related studiesen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
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