Structure determination, thermal stability and dissolution rate of δ-indomethacin

[Display omitted] •The unknown structure of the δ-indomethacin drug was solved by 3D electron diffraction.•The dissolution rate of the δ-polymorph is higher compared to other known polymorphs.•Solid-solid phase transformation from δ-polymorph to α-polymorph has been observed. The structure solution...

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Veröffentlicht in:International journal of pharmaceutics 2021-10, Vol.608, p.121067-121067, Article 121067
Hauptverfasser: Andrusenko, Iryna, Hamilton, Victoria, Lanza, Arianna E., Hall, Charlie L., Mugnaioli, Enrico, Potticary, Jason, Buanz, Asma, Gaisford, Simon, Piras, Anna M., Zambito, Ylenia, Hall, Simon R., Gemmi, Mauro
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Sprache:eng
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Zusammenfassung:[Display omitted] •The unknown structure of the δ-indomethacin drug was solved by 3D electron diffraction.•The dissolution rate of the δ-polymorph is higher compared to other known polymorphs.•Solid-solid phase transformation from δ-polymorph to α-polymorph has been observed. 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 better biopharmaceutical properties 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2021.121067