Estimation of the transition temperature for an enantiotropic polymorphic system from the transformation kinetics monitored using Raman spectroscopy.

Polymorphism is a frequently encountered phenomenon in organic materials and is particularly important for pharmaceuticals. For enantiotropically related polymorphs, one important property of the polymorphic pair is the thermodynamic transition temperature. The transition temperature is sometimes difficult to determine experimentally due to the rapid transformation between the two polymorphic forms in solution. Due to its relatively rapid spectral acquisition rate, as well as the possibility of in-line monitoring, Raman spectroscopy is ideally suited to monitoring the kinetics of transformation between different solid-state forms. In this study, it was demonstrated that the transition temperature could be estimated from polymorphic transformation profiles obtained from real-time in situ Raman data. Using this method, the estimated transition temperature for flufenamic acid was in good agreement with the previously published value. These results suggest that Raman spectroscopy may be a useful method to determine transition temperatures in systems not amenable to other methods.