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

Abstract

Pressure-induced transformation of ␥-IMC ͓1-͑p-chlorobenzoyl͒-5-methoxy-2-methylindole-3-acetic acid͔ is analyzed from Raman scattering investigations in the low-frequency range of 10-250 cm −1 and the high frequency region between 1550 and 1750 cm −1 , where C v O stretching vibrations are usually observed. At room temperature, by pressurization from atmospheric pressure up to 4 GPa, ␥-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 ␣ form, which is denser than the ␥ form and metastable with respect to ␥-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 liquid͒, 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.

Low-frequency vibrational properties of crystalline and glassy indomethacin probed by terahertz time-domain spectroscopy and low-frequency Raman scattering

“…Up to now, these spectra were also separately obtained in Refs. [3][4][5]. In this study, a direct comparison between the IR and low frequency Raman spectra of the c-IMC is done.…”

“…IMC easily undergoes a liquid-glass transition at the glass transition temperature, T g = 315 K upon cooling from the melt. It then exhibits physical properties similar to typical structural glasses [1][2][3][4][5].…”

“…Also, these kinds of measurements have been used for the crystalline and glassy IMC [1][2][3][4][5][7][8][9]. In particular, several spectroscopic studies of crystalline and glassy (amorphous) IMCs have already been reported [3][4][5][7][8][9].…”

Physical vapor deposition as a route to hidden amorphous states

“…1). There has been a recent report of pressure-induced polyamorphism in IMC based on shifts of peaks in the Raman spectra (46). Preliminary Raman experiments on samples vapor-deposited at T substrate ϭ 265 K and 0.2 nm/s show no change upon annealing, indicating that vapordeposition does not access the same packing configurations that are obtained through pressurization.…”

Interrelationships Between Structure and the Properties of Amorphous Solids of Pharmaceutical Interest

“…13 To date, only a few systems of pharmaceutical interest have been demonstrated to exhibit such behavior, for example, supercooled water at very low temperatures and high pressures 14 and supercooled D-mannitol under ambient conditions. 15 Other studies with amorphous indomethacin have provided some evidence that polyamorphism may occur for samples prepared by compression of the crystal under high pressure 16 and when the glass is formed from vapor deposition. 17 Clearly, in all these cases of polyamorphism, a better understanding of the structural features of supercooled liquids and glasses that might give rise to different energy states in such systems is of great importance, as has been recently discussed.…”