Determination of End-points for Polymorph Conversions of Crystalline Organic Compounds Using On-line Near-infrared Spectroscopy

Abstract

Trovafloxacin mesylate exists in two anhydrous polymorphic forms, I and II. The fundamental band vibration spectra information does not readily differentiate between the two forms, although the crystal lattice of each form has a distinct X-ray powder diffraction pattern. Subtle spectral differences between the two polymorphs can be detected in the NIR spectral region and the interconversion of the two forms can be monitored in hot solvent crystal slurries using NIR spectroscopy and an on-line fibre optic probe. A generally applicable method has been developed to monitor the conversion of form I into form II as a crystal slurry. The free energy profile in principal component space has been modelled as the process proceeds to give a computer graphic of the change which readily shows when the conversion is complete.