Article Metrics


Online attention

Sulfamerazine: Understanding the Influence of Slip Planes in the Polymorphic Phase Transformation through X-Ray Crystallographic Studies and ab Initio Lattice Dynamics

DOI: 10.1021/acs.molpharmaceut.5b00504 DOI Help
PMID: 26317333 PMID Help

Authors: Anuradha R. Pallipurath (National University of Ireland) , Jonathan M. Skelton (University of Bath) , Mark R. Warren (Diamond Light Source) , Naghmeh Kamali (National University of Ireland) , Patrick Mcardle (National University of Ireland) , Andrea Erxleben (National University of Ireland)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Pharmaceutics , VOL 12 (10) , PAGES 3735 - 3748

State: Published (Approved)
Published: October 2015

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.

Journal Keywords: Sulfamerazine; polymorphism; thermal expansion; lattice dynamics; phase transitions; synchrotron X-ray diffraction; slip planes

Subject Areas: Chemistry

Instruments: I19-Small Molecule Single Crystal Diffraction

Added On: 06/01/2016 12:09

Discipline Tags:

Technical Tags: