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Indomethacin.pdf (950.04 kB)

Structure Determination, Thermal Stability and Dissolution Rate of δ Indomethacin

submitted on 03.06.2021, 08:08 and posted on 04.06.2021, 06:18 by Iryna Andrusenko, Victoria Hamilton, Arianna E. Lanza, Charlie L. Hall, Enrico Mugnaioli, Jason Potticary, Asma Buanz, Simon Gaisford, Anna Piras, Ylenia Zambito, Simon R. Hall, Mauro Gemmi

The structure solution of the δ-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied α- and γ-polymorphs, indicating an increased bioavailability for medicinal applications. The structure was solved in non-centrosymmetric space group P21 and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for δ-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid-solid transition from δ-polymorph to α-polymorph that can be driven by similarities in molecular conformation.


Engineering and Physical Sciences Research Council UK (Grants EP/L016648/1 and EP/L015544/1)

Regione Toscana he FELIX project (POR CREO FERS 2014 2020)

European Union’s Horizon 2020 Research and Innovation programme MagnaPharm project (Grant Agreement Number 73689)


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Istituto Italiano di Tecnologia



ORCID For Submitting Author


Declaration of Conflict of Interest

no conflict of interest

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