Characterisation of organic solid forms and real-time in situ monitoring of their transformations using solid-state fluorescence

Abstract

We demonstrate the application of solid-state fluorescence spectroscopy for the real-time monitoring and characterisation of solid forms (e.g. polymorphs, solvates, cocrystals) of pharmaceutical molecules. This proof-of-principle study focuses on the pharmaceutical indomethacin which, although poorly fluorescent in solution, in the solid state yields highly fluorescent amorphous, polymorphic, solvate and cocrystal forms. We show that solid forms of indomethacin can be readily distinguished by their fluorescent properties and, by using a simple and readily available experimental set-up, we reveal that fluorescence spectroscopy can be used to quantify amorphous and crystalline forms in a mixture and to monitor the kinetics of their interconversion in situ and in real-time (30 seconds resolution or less).