title: Probing phase transitions in simvastatin with terahertz time-domain spectroscopy.
abstract: Simvastatin is known to exist in at least three polymorphic forms. The nature of polymorphism in simvastatin is ambiguous, as the crystal structures of the polymorphs do not show any significant change in crystal packing or molecular conformation. We utilize terahertz time-domain spectroscopy to characterize each of the polymorphs and probe the phase transitions in the range of 0.2-3.0 THz and for temperatures ranging from 90 to 390 K. In form III, vibrational modes are observed at 1.0, 1.25, and 1.7 THz. For form I, we find that the spectrum is dominated by a baseline corresponding to libration-vibration motions coupled to the dielectric relaxations, which is characteristic of a disordered hydrogen bonding material but with additional broad vibrational modes at 0.8 and 1.4 THz. In addition, the baseline shifts with temperature similar to that observed in disordered materials. This background absorption exhibits pronounced changes around the phase transition temperatures at 232 and 272 K. The results are in agreement with molecular dynamics simulations, which indicate that changes in the rotational freedom of the ester tail in the molecule govern the polymorphism in simvastatin.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge , Pembroke Street, Cambridge CB2 3RA, United Kingdom.
authors.forename: Nicholas Y
authors.initials: NY
authors.lastname: Tan
authors.forename: J Axel
authors.initials: JA
authors.lastname: Zeitler
mesh_terms: D001702:Biopharmaceutics; D006801:Humans; D006860:Hydrogen Bonding; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009038:Motion; D044367:Phase Transition; D019821:Simvastatin / Q000737:chemistry*; D013696:Temperature; D055068:Terahertz Spectroscopy; D014732:Vibration
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: disordered crystal; phase transition; simvastatin; spectroscopy; terahertz