Characterization of crystalline polymorphs and their quantitation has become an integral part of the pre-clinical drug development process. Raman spectroscopy is a powerful technique for the rapid identification of phases of pharmaceuticals. In the present work we demonstrate the use of low wavenumber Raman vibrational spectroscopy (including phonon measurement) for discrimination among polymorphs. A total of 10 polymorphic pharmaceuticals were employed to conduct a critical assessment. Raman scattering in the low frequency region (10–400 cm−1), which includes crystal lattice vibrations, has been analyzed and the results indicate lattice phonon Raman scattering can be used for rapid discrimination of polymorphic phases with additional discriminating power compared to conventional collection strategies. Moreover structural insight and conformational changes can be detected with this approach.

Polymer-induced heteronucleation (PIHn), a powerful crystalline polymorph discovery method, has revealed two novel polymorphs of the low solubility bioenhancer piperine. Both of these forms exhibit enhanced solubility when compared to the commercial polymorph, thereby potentially improving the efficacy of piperine as a bioenhancer. Structural comparison of the three forms reveals that π-π interactions are only present in the two newly discovered forms. Combined with the stability data this reveals that despite the extended conjugation present in the moleculesuch interactions are not preferred in thesolid state.