Terahertz and Raman Spectroscopic Investigation of Anti-tuberculosis Drug-Drug Cocrystallization Involving 4-aminosalicylic Acid and Pyrazinamide

Abstract

Drug-drug cocrystals can enhance the dissolution rate, oral bioavailability as well as increase their stability and hygroscopicity. In this paper, the anti-tuberculosis drug-drug cocrystal between pyrazinamide (PZA) and 4-aminosalicylic acid (PASA) was prepared with the water-assisted grinding approach. The parent materials and corresponding 1:1 molar ratio binary PASA-PZA cocrystal have been characterized by applying the terahertz time-domain (THz-TDS) and Raman spectroscopy. The THz absorption spectra presented that there were significantly different peaks between the parent materials and the drug-drug cocrystal. Raman spectral results also indicated the differences of such cocrystal compared with the starting compounds. In addition, density functional theory (DFT) calculations were employed for simulating the structure of PASA-PZA cocrystal and provide its vibrational modes assignment. All of our results offered a unique means to characterize the conformation of specific PASA-PZA drug-drug cocrystals at the molecule-level, providing a great deal of information about the cocrystals’ formation and also both intramolecular and/or inter-molecular hydrogen bond interactions within the emerging solid-state pharmaceutical fields.