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An insight into the role of additives in controlling polymorphic outcome: a CO2-antisolvent crystallization process of carbamazepine

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Show simple item record Padrela, Luis Zeglinski, Jacek Ryan, Kevin M. 2017-12-15T12:14:14Z 2017
dc.description peer-reviewed en_US
dc.description.abstract Controlling pharmaceutical polymorphism in crystallization processes represents a major challenge in pharmaceutical science and engineering. For instance, CO2-antisolvent crystallization typically favors the formation of metastable forms of carbamazepine (CBZ), a highly polymorphic drug, with impurities of other forms. This work demonstrates for the first time that a supercritical CO2- antisolvent crystallization process in combination with certain molecular additives allows control of the polymorphic outcome of carbamazepine. We show herein that in the presence of sodium stearate and Eudragit L-100, needle-shaped crystals of CBZ form II are obtained, while blocky-shaped crystals of CBZ form III are obtained in the presence of Kollidon VA64, sodium dodecyl sulfate, ethyl cellulose and maltitol. This selectivity for pure forms in this supercritical set up contrasts to the results when the same set of additives where used in a solvent evaporation method that yielded mixtures of form I, II and III. The type of additive used in the CO2-antisolvent crystallization process impacted both the product crystals polymorphic form and size. A detailed molecular-level analysis along with DFT calculations allowed us to give a mechanistic insight into the role of sodium stearate and Eudragit L-100 in facilitating nucleation of the metastable form II. en_US
dc.language.iso eng en_US
dc.publisher American Chemical Society en_US
dc.relation.ispartofseries Crystal Growth and Design;17 (9), pp. 4544-4553
dc.rights © 2017 ACS This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal Title, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see en_US
dc.subject crystallization en_US
dc.subject carbamazepine en_US
dc.title An insight into the role of additives in controlling polymorphic outcome: a CO2-antisolvent crystallization process of carbamazepine en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1021/acs.cgd.7b00163
dc.contributor.sponsor SFI en_US
dc.contributor.sponsor ICHEC en_US
dc.relation.projectid 12/RC/2275 en_US
dc.relation.projectid 15/US-C2C/I3133 en_US 2018-07-10
dc.embargo.terms 2018-07-10 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2724358

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