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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 3; p. 488
• Main Authors: Wang, Qiqi, Xue, Jiadan, Hong, Zhi, Du, Yong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-01-2019; MDPI
• Subjects: 3-hydroxybenzoic acid; Absorption; Absorption spectra; Acids; Carboxyl group; Chemical bonds; Crystallization; Density functional theory; Hydrogen Bonding; Hydrogen bonds; Hydroxybenzoates - chemistry; Investigations; Models, Molecular; Molecular Structure; NMR; Nuclear magnetic resonance; p-Hydroxybenzoic acid; Pharmaceuticals; Pyrazinamide; Pyrazinamide - chemistry; R&D; Raman spectra; Raman spectroscopy; Raw materials; Research & development; Simulation; Single crystals; Solvents; Spectroscopy; Spectrum analysis; Spectrum Analysis, Raman; Terahertz frequencies; Terahertz Spectroscopy; terahertz time-domain spectroscopy; Tuberculosis; Vibration; Vibrational spectra; 3-hydroxybenzoic acid; Raman spectroscopy; terahertz time-domain spectroscopy; density functional theory; pyrazinamide
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24030488

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.