Broadband Dielectric Relaxation Study at Ambient and Elevated Pressure of Molecular Dynamics of Pharmaceutical: Indomethacin

Abstract

Broadband dielectric measurements on the pharmaceutical indomethacin (IMC) were performed at ambient and elevated pressure. Data on molecular dynamics collected at ambient pressure are in good agreement with that published in the literature. In the glassy state, there is a well-resolved secondary relaxation with Arrhenius activation energy E(a) = 38 kJ/mol. This commonly observed relaxation process (labeled gamma) is of intramolecular origin because it is pressure-insensitive. Closer analysis of the ambient pressure dielectric spectra obtained in the vicinity of the T(g) indicated the presence of one more secondary relaxation (beta), which is slower than that commonly observed. Application of the CM predictions enabled us to classify it as a true JG relaxation. Pressure measurements confirmed our supposition concerning the origins of the two secondary relaxations in IMC. Moreover, we have found that IMC under pressure does not crystallize, even at very high temperatures of T > or = 372 K. This finding was discussed in the framework of the two-order parameter model proposed by Tanaka (Konishi, T.; Tanaka, H. Phys. Rev B 2007, 76, 220201), as well as the JG relaxation proposal by Oguni (Hikima T.; Hanaya M.; Oguni M. J. Mol Struct. 1999, 479, 245). We also showed that the shape of the alpha-relaxation loss peak is the same when comparing dielectric spectra with the same tau(alpha) but obtained at ambient and elevated pressure. Additionally, we found out that the fragility of IMC decreases with increasing pressure. In addition, the pressure coefficient of the glass transition temperature, dT(g)/dP, was determined, and it is 255 K/GPa. Finally, we discuss the possibility of preparation of the amorphous state with higher density than by cooling of the liquid.

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

“…In contrast to the spectra of normal liquids below 1.0 THz [13][14][15], e 00 (m) of the glassy IMC does not show the tail of the dielectric relaxation processes. This is mainly because the relaxation processes shift to a lower frequency range due to the liquid-glass transition [1,2]. Fig.…”

“…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].…”

“…However, one concern is the instability of the glassy state originating from the disordered structure and the http aging effect. Therefore, it is crucial to make clarify the molecular dynamics in the glassy states of the pharmaceutical system for obtaining a predictable stability [1,2]. In addition, these kinds of studies will provide new insights into understanding the universality in the dynamics of glass transitions on complex molecules.…”

“…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].…”

Interaction of Human Serum Albumin with Indomethacin: Spectroscopic and Molecular Modeling Studies

“…1). Individuals treated with such drugs are relieved of fever, pain, stiffness and swelling [9]. Several studies have also shown that indomethacin is an immunomodulator that augments macrophage, T cell, and natural killer cell activities and regulates the production of cytokines.…”