Determining the relative physical stability of anhydrous and hydrous crystal forms of GW2016

Abstract

The slurry equilibration method used to determine the relative physical stability of polymorphs is extended to a crystal system of an anhydrate and hydrate. The method involves preparation of organic/aqueous slurries of known water activity containing mixtures of the anhydrate and hydrate forms. The slurries equilibrate to the lowest free energy form, from which the relative physical stability is determined as a function of relative humidity. The method is particularly valuable when one or more of the crystal forms is kinetically stable, since solvent-mediated transformation accelerates the conversion process. Results are provided for GW2016 anhydrate and monohydrate crystal forms, for which it was determined that interconversion occurs between 7 and 15% relative humidity.