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dc.contributor.authorPallipurath, Anuradha R.
dc.contributor.authorSkelton, Jonathan M.
dc.contributor.authorWarren, Mark R.
dc.contributor.authorKamali, Naghmeh
dc.contributor.authorMcArdle, Patrick
dc.contributor.authorErxleben, Andrea
dc.identifier.citationPallipurath, Anuradha R., Skelton, Jonathan M., Warren, Mark R., Kamali, Naghmeh, McArdle, Patrick, & Erxleben, Andrea. (2015). Sulfamerazine: Understanding the Influence of Slip Planes in the Polymorphic Phase Transformation through X-Ray Crystallographic Studies and ab Initio Lattice Dynamics. Molecular Pharmaceutics, 12(10), 3735-3748. doi: 10.1021/acs.molpharmaceut.5b00504en_IE
dc.description.abstractUnderstanding the polymorphism exhibited by organic active-pharmaceutical ingredients (APIs), in particular the relationships between crystal structure and the thermodynamics of polymorph stability, is vital for the production of more stable drugs and better therapeutics, and for the economics of the pharmaceutical industry in general. In this article, we report a detailed study of the structure property relationships among the polymorphs of the model API, Sulfamerazine. Detailed experimental characterization using synchrotron radiation is complemented by computational modeling of the lattice dynamics and mechanical properties, in order to study the origin of differences in millability and to investigate the thermodynamics of the phase equilibria. Good agreement is observed between the simulated phonon spectra and mid-infrared and Raman spectra. The presence of slip planes, which are found to give rise to low-frequency lattice vibrations, explains the higher millability of Form I compared to Form II. Energy/volume curves for the three polymorphs, together with the temperature dependence of the thermodynamic free energy computed from the phonon frequencies, explains why Form II converts to Form I at high temperature, whereas Form III is a rare polymorph that is difficult to isolate. The combined experimental and theoretical approach employed here should be generally applicable to the study of other systems that exhibit polymorphism.en_IE
dc.description.sponsorshipA.R.P. would like to thank the Synthesis and Solid State Pharmaceutical Center (SSPC) and Science Foundation Ireland SFI (Grant No. [07/SRC/B1158]) for funding the current work, and also Dr. Jennifer Connolly (Department of Physiology, National University of Ireland) for help with acquiring the Raman spectra. J.M.S. gratefully acknowledges financial support from an EPSRC Programme Grant (Grant No. EP/K004956/1). We also thank the ICHEC, which maintains Fionn, the Irish HPC system, for making our computational study possible through time allocated through the project code ngche019c.en_IE
dc.publisherAmerican Chemical Societyen_IE
dc.relation.ispartofMolecular Pharmaceuticsen
dc.subjectGeneralized gradient approximationen_IE
dc.subjectAugmented wave methoden_IE
dc.subjectIn-vitro releaseen_IE
dc.subjectRaman spectroscopyen_IE
dc.subjectCrystal structureen_IE
dc.subjectLocal densityen_IE
dc.subjectAll electronen_IE
dc.subjectThermal expansionen_IE
dc.subjectLattice dynamicsen_IE
dc.subjectPhase transitionsen_IE
dc.subjectSynchrotron X-ray diffractionen_IE
dc.subjectSlip planesen_IE
dc.titleSulfamerazine: Understanding the influence of slip planes in the polymorphic phase transformation through X-ray crystallographic studies and ab initio lattice dynamicsen_IE
dc.local.contactAndrea Erxleben, School Of Chemistry, Room 150, Arts/Science Building, Nui Galway. 2483 Email:

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