New Polymorph of Indomethacin: Screening by Solid-State Guest Exchange and Characterization Using Fast Scanning Calorimetry

Solid-state guest exchange is used as an efficient method to prepare very metastable polymorphs of indomethacin, including the polymorph observed earlier only in a mixture with a polymeric solvent and a new crystalline form of this drug with a negligibly small amount of the included solvent (guest). The used preparation procedure gives less stable inclusion compounds of indomethacin, which require a milder desolvation treatment than inclusion compounds formed in binary host–guest systems, so the metastable forms with a low first melting point can be prepared. For the characterization of indomethacin polymorphs, fast scanning calorimetry was used, along with conventional characterization methods. This method merges multistep polymorphic transitions, making the first melting point much more pronounced, so the different polymorphs become better discriminated.