Crystallization Behavior and Relaxation Dynamics of Supercooled S-Ketoprofen and the Racemic Mixture along an Isochrone

Abstract

In this paper, we study crystallization behavior and molecular dynamics in the supercooled liquid state of the pharmaceutically important compound ketoprofen at various thermodynamic conditions. Dielectric relaxation for a racemic mixture was investigated in a wide range of temperatures and pressures (up to 350 MPa), whereas crystallization kinetics for racemic and single enantiomers was studied along a (T, p) curve characterized by the same structural relaxation time, τα ≅ 10–6 s, a so-called isochrone. The aim was to investigate the effect of pressure on the crystallization tendencies of pure enantiomers and their 50–50 equimolar mixture in the metastable supercooled liquid state. Crystallization kinetic studies revealed that at the same isochronal conditions the behavior of the S-enantiomer and R,S-racemic mixture of ketoprofen is entirely different. This was examined in the context of previous results and in view of the possibility of inducing changes in the enantiomeric composition or enantiomers separation from a racemic mixture as the effect of high pressure.