Broadband Terahertz Time-Domain and Low-Frequency Raman Spectroscopy of Crystalline and Glassy Pharmaceuticals

Abstract

The applications of the broadband Terahertz Time-Domain Spectroscopy (THz-TDS) and the low-frequency Raman scattering spectroscopy to glassy and crystalline pharmaceuticals were reviewed. The real and imaginary parts of a complex dielectric constant were measured by the transmission of THz-TDS using a pure pellet without mixing polyethylene in the frequency range from 0.2 to 6.5 THz. The low-frequency Raman spectra were measured down to 0.3 THz using a double-grating spectrometer. In crystalline indomethacin, indapamide, and racemic ketoprofen, the clear difference in peak frequencies was observed between THz dielectric and low-frequency Raman scattering spectra. It can be attributed to the mutual exclusion principle between Raman and IR activities of optical vibrational modes in centrosymmetric crystals. In glassy indomethacin the broad peak at 3.0 THz in the IR spectrum is attributed to the infrared active intermolecular vibrational mode of the hydrogen bonded cyclic dimers, which is centrosymmetric. The boson peak is the well-known low-energy excitation reflecting vibrational density of states in glassy or amorphous materials. The boson peaks of glassy indomethacin were clearly observed at about 0.3 THz and 0.5 THz in THz-TDS and Raman scattering spectra, respectively. The difference in peak frequencies is attributed to the different frequency dependence between IR-vibration and Raman-vibration coupling constants.

Use of Terahertz-Raman Spectroscopy to Determine Solubility of the Crystalline Active Pharmaceutical Ingredient in Polymeric Matrices during Hot Melt Extrusion

“…These phase transitions were monitored in the low-frequency THz-Raman spectral region that covers the Stokes signal (5–200 cm –1 ) and provides information about the crystal lattice vibration (phonon) modes. 34,35 Such vibrations are sensitive to local order and disorder, enabling distinction between different crystal packing arrangements, including the amorphous and crystalline states. 36,37…”

Boson peak dynamics of glassy glucose studied by integrated terahertz-band spectroscopy

“…This indicates that these polyhydric alcohols [71] have a linear frequency dependence on C IR (ν). On the other hand, the pharmaceutical IMC glass, which is also a hydrogenbonded organic glass, shows a significant discrepancy between ν BP−IR [8,9] and ν BP−Raman [8,9,81], and ν BP−IR /ν BP−Raman ∼ 0.6 [8,9,81]. The different tendency of the ratio from the polyhydric alcohols suggests that C IR (ν) of IMC will obey Taraskin's model.…”

“…Numerous studies have been done regarding the BP dynamics; however, the microscopic origin is not yet fully understood. Furthermore, there have been almost no recent THz spectroscopic studies of the BP dynamics reported [6][7][8][9][10], in spite of advanced development of the technique of the THz light source and detection.…”

“…Naftaly and Miles [6] recognized this, and they represented the BP as α(ν)/ν 2 , although this recognition has not spread to other researchers in the fields of glass systems and THz spectroscopy. Recently, we pointed out that the BP in the sense of α(ν)/ν 2 is detectable by THz-TDS for the pharmaceutical indomethacin (IMC) glass [8,9], which is one of the organic glass formers; then some researchers noticed it [10] or rerecognized the potential of the THz-TDS for detection of the BP. Consequently, THz-TDS is a suitable technique to detect the BP.…”

Terahertz Spectroscopy in Advanced Materials Science

“…In this chapter, Recent progress of terahertz vibrational spectroscopy using THz-time-domain spectroscopy (THz-TDS) [3], THz time-domain spectroscopic ellipsometry (THz-TDSE) [4], and far-infrared spectroscopy is reviewed in advanced materials science on the following three kinds of materials. (1) Pharmaceuticals: studies of terahertz vibrational spectroscopy on polymorphism of crystalline states and glassy states on typical pharmaceuticals [5]. (2) Ferroelectric materials: studies of terahertz vibrational spectroscopy on optical phonons, ferroelectric soft mode, and phonon-polariton dispersion relation on typical ferroelectric crystals for optical application [6].…”