Spectral characterization and vibrational mode study of cocrystal of acetaminophen and aspirin based on terahertz/Raman spectroscopy combined with DFT theory calculation

In recent years, pharmaceutical cocrystal has become a hot field in drug development, which improves the solubility, stability, and bioavailability of drugs. This article focuses on the study of acetaminophen and aspirin, measuring their individual terahertz (THz) absorption spectra, as well as their THz absorption spectra after physical grinding and mixing in a 1: 1 M ratio. Then they were dissolved in anhydrous ethanol in the same molar ratio, and the THz spectra of the cocrystal were extracted and measured. The THz spectrum technology was successfully used to distinguish acetaminophen, aspirin and their cocrystal substances. The absorption peaks of the cocrystal within the THz spectra exhibit a significant disparity when compared to that of the physical mixture of acetaminophen and aspirin. The reason is that chemical changes occur during the formation of the cocrystal, which is also proved by Raman spectrum characterization. Then, density functional theory (DFT) is applied to simulate the interaction between acetaminophen and aspirin and the formation of new hydrogen bonds between cocrystal substances, and provide corresponding vibration modes. In addition, colorimetric experiments were conducted to demonstrate the higher stability of acetaminophen-aspirin cocrystal. These results provide us with a distinct approach to characterize the composition of cocrystal structures. This approach can be employed to boost the pharmacological activity as well as the physical attributes of particular drugs from the molecular dimension.