Pharmaceutical Cocrystal Formation of Pyrazinamide with 3-Hydroxybenzoic Acid: A Terahertz and Raman Vibrational Spectroscopies Study

Abstract

Vibrational modes of pyrazinamide (PZA), 3-hydroxybenzoic acid (3-hBA), and their cocrystal were characterized using terahertz time-domain (THz-TDS) and Raman vibrational spectroscopic techniques. In experimental THz spectra, the cocrystal has characteristic absorption bands at around 0.81, 1.47, and 1.61 THz, respectively, meanwhile the raw materials are absolutely different in this region. Raman spectra also show similar results about differences between the cocrystal and corresponding starting parent materials. Density functional theory (DFT) was used to simulate both optimized structures and vibrational modes of the cocrystal formed between PZA and 3-hBA. The vibrational modes of such cocrystal are assigned through comparing the simulation DFT frequency results with experimental vibrational spectra. The calculation of the theoretical THz spectrum shows that the hydrogen bonding effect established between H11–N12–H13 and the carboxyl group -COOH makes contributions to the formation of absorption peaks in 0.49, 0.62, 0.83, and 1.61 THz, which agrees pretty well with experimental results. The theoretical Raman result also matches well with experimental observations. The results provide a fundamental benchmark for the study of pharmaceutical cocrystal formation and also inter-molecular hydrogen bonding interactions between active pharmaceutical ingredients and various cocrystal coformers based on Raman and terahertz vibrational spectroscopic techniques combined with theoretical simulations.

Non‐Local Electron‐Phonon Interaction in Naphthalene Diimide Derivatives, its Experimental Probe and Impact on Charge‐Carrier Mobility

“…We will consider the off-resonance case, that is, the excitation wavelength will be far longer than those of electronic transitions. As mentioned above, the OSC polarizability is associated with the molecular polarizabilities and J. Mediumfrequency (MF, 200 cm −1 < ω < 1800 cm −1 ) and high-frequency (ω > 1800 cm −1 ) vibrations of organic crystals without conventional intermolecular hydrogen bonds [39][40][41] are generally intramolecular, [2,10,42] and the Raman intensities of the corresponding bands describe the abilities of these vibrations to modulate the molecular polarizability but not J. [43] Thus, the MF range is out of the scope of this study; nevertheless, we briefly discuss it in Section S8, Supporting Information.…”

Transformation of terahertz vibrational modes of cytosine under hydration

“…The lengths of the hydrogen bonds between the C ketone groups and the hydrogen atoms of water molecules were 1.781 Å for O1⋯H21-O5 and 1.735 Å for O1⋯H27-O7. The C-MH hydrogen bonds were stronger and more abundant than those of C, which leads to different intermolecular interactions of C molecules and a more stable crystal structure with new cell parameters, i.e., the co-crystallization process 12,44 . Also, a change in the molecule's environment and conformation leads to a characteristic change in the THz spectra.…”

“…As a result, they have been studied in the terahertz (THz) frequency region, such as the Debye relaxation process of liquid water 6,7 , the retardation of water dynamics with a solute 8 , and the dynamics of hydration water around protein 9 . The THz frequency range is associated with the low-frequency vibrational modes, including the collective vibrations of intermolecular and intramolecular interactions 10 , the phonon modes of crystalline molecules 11 , and in-plane and out-of-plane bending vibrations of many molecules 12 . THz time-domain spectroscopy (THz-TDS) has been utilized in the study of such vibrational characteristics of biomolecules [13][14][15][16][17][18] , as well as in identifying biological functions [19][20][21] , and in applications to biomedical, pharmaceutical, and clinical industries [22][23][24][25][26][27][28][29][30] .…”

The Benefits and Challenges of Antibiotics–Non-Steroidal Anti-Inflammatory Drugs Non-Covalent Reaction

“…Raman spectroscopy has also been utilized to detect the presence of water molecules in the crystal lattice [64], for example, by analyzing the unique ciprofloxacin salicylate 1.75 hydrate [65]. Finally, Terahertz spectroscopy also has been used to identify new solid phase construction; for example, it has been previously used to determine pyrazinamide-3-hydroxybenzoic acid [68].…”