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

Pressure-induced transformation of γ-IMC [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid] is analyzed from Raman scattering investigations in the low-frequency range of 10--2500.3em0excm^-1 and the high frequency region between 1550 and 17500.3em0excm^-1, where CO stretching vibrations are usually observed. At room temperature, by pressurization from atmospheric pressure up to 40.3em0exGPa, γ-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 α form, which is denser than the γ form and metastable with respect to γ-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.