LAUSR

ABSTRACT As crystalline indomethacin is heated and subsequently cooled, it transforms into glassy indomethacin. While the original crystals are off‐white in color, the glass becomes blackish‐brown via a yellow intermediate stage. TLC of the components of the glass revealed three bands. The yellow component, which is generated either under hypoxic conditions or in the dark, was elucidated by NMR spectroscopy to be a decarboxylated fragment produced by thermal degradation. The colorless component is proposed to be formed by the opening of the indole ring of indomethacin; the structure of this degradation product was identified by EI‐MS to be the same as the oxidative‐cleavage product formed upon UV‐irradiation, as previously reported. Another band was a blackish‐brown pigment whose mobility placed it close to the TLC baseline. This oxidative‐cleavage product and the blackish‐brown pigment are not generated under hypoxic conditions. However, the extent of indomethacin decarboxylation under hypoxic conditions was found to be dependent on the heating temperature and time. Consequently, we prepared amorphous indomethacin through control of the heating temperature and time; heating at 160°C for 30min or less under hypoxic conditions is optimum for obtaining pure amorphous indomethacin.