title: Sulfamerazine: Understanding the Influence of Slip Planes in the Polymorphic Phase Transformation through X-Ray Crystallographic Studies and ab Initio Lattice Dynamics.
abstract: Understanding 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.
authors: School of Chemistry, National University of Ireland , Galway, Ireland.
authors: Anuradha R
authors: AR
authors: Pallipurath
authors: Department of Chemistry, University of Bath , Claverton Down, Bath BA2 7AY, United Kingdom.
authors: Jonathan M
authors: JM
authors: Skelton
authors: Beamline I19, Diamond Light Source , Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE, England.
authors: Mark R
authors: MR
authors: Warren
authors: School of Chemistry, National University of Ireland , Galway, Ireland.
authors: Naghmeh
authors: N
authors: Kamali
authors: School of Chemistry, National University of Ireland , Galway, Ireland.
authors: Patrick
authors: P
authors: McArdle
authors: School of Chemistry, National University of Ireland , Galway, Ireland.
authors: Andrea
authors: A
authors: Erxleben
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D013416:Sulfamerazine / Q000737:chemistry*; D017356:Synchrotrons; D013816:Thermodynamics
chemical_list: D013416:Sulfamerazine
keywords: Sulfamerazine; lattice dynamics; phase transitions; polymorphism; slip planes; synchrotron X-ray diffraction; thermal expansion