Discovery of a new stable polymorph of 4-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)quinazolinium methanesulfonate using near-infrared spectroscopy to monitor form change kinetics

Abstract

Polymorphism is an important property of crystalline organic molecules, particularly when used to develop medicines. Discovery of all the polymorphs in a series is often difficult. This paper highlights the use of near-infrared spectroscopy to monitor the kinetics of form changes of polymorphs and solvates (hydrates). In the case of mesylate salt 5, this led to the discovery of a new preferred form. Identification and confirmation of unique polymorph crystal states are determined using X-ray powder diffraction patterns. This complements and confirms the kinetic change observed in the near-infrared. The technique is generally applicable to the study of two-phase solid–liquid crystal slurries under isothermal conditions.