Crystallization and Phase Changes in Paracetamol from the Amorphous Solid to the Liquid Phase

Abstract

For the case of paracetamol, we show how terahertz time-domain spectroscopy can be used to characterize the solid and liquid phase dynamics. Heating of supercooled amorphous paracetamol from 295 K in a covered sample under vacuum leads to its crystallization at 330 K. First, form III is formed followed by the transformation of form III to form II at 375 K, to form I at 405 K, and finally melting is observed around 455 K. We discuss the difference between the featureless spectra of the supercooled liquid and its liquid melt. Lastly, we studied the onset of crystallization from the supercooled liquid in detail and quantified its kinetics based on the Avrami–Erofeev model. We determined an effective rate constant of k = 0.056 min–1 with a corresponding onset of crystallization at T = 329.5 K for a heating rate of 0.4 K min–1.

Terahertz Time-Domain and Low-Frequency Raman Spectroscopy of Organic Materials

“…131 Due to the high sensitivity of THz-TDS to intermolecular interactions, it was possible to determine the onset of crystallization very precisely and quantify the crystallization kinetics. Following the crystallization into form III, further phase transitions to forms II and I were observed before the sample melted.…”

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

“…According to these studies, the relaxation process and intermolecular stretching mode were observed. The dynamics of organic glass forming materials, such as polymers, poly-alcohols, sugars, and pharmaceutics, were investigated in the frequency of 0.2-3.0 THz using THz-TDS [16][17][18][19][20]. It is expected that the low-energy excitations of glassy materials such as a boson peak, intermolecular vibrations, and fast relaxation processes, can be studied by THz-TDS [21].…”

A systematic study of the isothermal crystallization of the mono-alcohol n-butanol monitored by dielectric spectroscopy

“…Refs. [8][9][10][11][12][13]. The sign of crystallization is a decrease in intensity of the signal, and the crystal fraction/concentration of the sample is often obtained by assuming that the relaxation strength is proportional to the volume fraction of liquid in the sample [14][15][16].…”