Evidence for a high-density amorphous form in indomethacin from Raman scattering investigations

Abstract

Pressure-induced transformation of $\gamma$-IMC [1-($p$-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid] is analyzed from Raman scattering investigations in the low-frequency range of $10–250{\mathrm{cm}}^{-1}$ and the high frequency region between 1550 and $1750{\mathrm{cm}}^{-1}$, where $\mathrm{C}\mathrm{O}$ stretching vibrations are usually observed. At room temperature, by pressurization from atmospheric pressure up to $4\mathrm{GPa}$, $\gamma$-IMC undergoes a collapse transformation into a high-pressure crystalline form, induced by large rearrangement in the hydrogen-bonded network associated with molecular conformational changes. The Raman spectrum of the high-pressure crystal is similar to that of the $\alpha$ form, which is denser than the $\gamma$ form and metastable with respect to $\gamma$-IMC at atmospheric pressure. Upon further compression a solid-state amorphization is observed via the breakdown of hydrogen bonds. The Raman line shape of the high-pressure amorphous form is different from that of the vitreous state (or thermal glass obtained by quenching the liquid), suggesting the existence of a high-density amorphous state. By release of pressure, this high-density amorphous state transforms into the thermal glass. This transformation can be interpreted as a transformation between a high-density amorphous to a low-density amorphous state, which could be associated with a polyamorphic transformation.