Differentiation of solvatomorphs of active pharmaceutical ingredients (API) by solid-state vibrational circular dichroism (VCD)

[Display omitted] •Dutasteride as a model for demonstrating the utility of solid-state VCD for solvatomorphs study.•VCD is a complementary technique for identifying and differentiating several forms of API.•Solid-state VCD is a powerful tool to distinguish solvatomorphs.•Computational study of clusters of solvatomorphs can replicate features of the VCD spectrum. Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs – the model active pharmaceutical ingredient (API). Several crystalline DS hydrochloride hydrates solvated with methanol, ethanol, acetonitrile, acetone, and acetic acid were prepared. In contrast to almost identical IR spectra, the VCD ones were very sensitive to changes in the sample composition. We marked significant differences in the shape of VCD spectra of studied DS solvatomorphs, DS hydrates, and DS polymorphic forms. Our findings, supported by DFT calculations, show that VCD spectroscopy has the pronounced ability to distinguish their crystal arrangements. We believe that this contribution will extend the use of VCD in the pharmaceutical industry for developing and designing new chiral drug products for the identification, description, and in-depth probing of several pharmaceutical solvatomorphs in the future.