title: Observation of oscillatory behavior during the dissolution of a pharmaceutical compound and evidence for the existence of an inverse Ostwald rule.
abstract: Oscillatory kinetic behavior is reported for the first time in a solid-state phase transformation of an organic compound, specifically, in the dissolution of Form V crystals of etoricoxib in neat toluene. The dissolution involves kinetics of bistability due to the generation of a second polymorph, Form I, during the process. While an attempt is made to reconcile the periodic behavior with the oscillatory rate coefficient predicted by time-dependent Marcus theory, more successful simulations of the data are obtained using superimposed, elementary dispersive kinetic models for both dissolution and nucleation-and-growth. Contrastingly, the dissolution of Form V in toluene containing a suspected small quantity of methanol/base contaminant shows that the phase transformation of Form V to the less-stable Form I crystals is rate-limiting and that the process is well described by a single, elementary dispersive kinetic model (i.e., no oscillations are observed). The latter observation lends support to the bistability hypothesis and provides evidence for the existence of a 'corollary' to Ostwald's rule of stages.
authors.affiliation: Merck & Co., Inc., P.O. Box 2000, RY818-B205, 126 East Lincoln Avenue, Rahway, New Jersey 07065, USA. peter_skrdla@merck.com
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Skrdla
mesh_terms: D003460:Crystallization; D000077613:Etoricoxib; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry*; D013997:Time Factors; D014050:Toluene / Q000737:chemistry
chemical_list: D011725:Pyridines; D013450:Sulfones; D014050:Toluene; D000077613:Etoricoxib