Study on the cocrystal of arginine and acetylsalicylic acid using vibrational spectroscopy and DFT calculations.

Drug repositioning and reuse is a cost-effective strategy for the development of new drugs, and drug co-crystal is a fast and effective technical means. Acetylsalicylic acid is a BCS II drug, which has the limitations of high permeability and low solubility, and the safety and efficacy of the drug have been greatly affected. Co-crystallization with other forming agents is considered to be a promising technical means, which can not only increase the solubility, but also improve the dissolution rate and stability. In this paper, the cocrystal of acetylsalicylic acid and arginine was prepared by grinding method. The physical and chemical characterization of the raw material, the mixture and the obtained cocrystal was carried out by XRD, terahertz spectroscopy (THz-TDS) and Raman spectroscopy (Raman). The obvious difference was observed on the characteristic peaks of the cocrystal, which proved the formation of the cocrystal. Understanding the basic properties of lattice vibration during the eutectic process is challenging, yet it can be accomplished through theoretical calculations. By employing density-functional theory (DFT) calculations, the molecular configurations and vibration spectra of the two drug cocrystals can be obtained, enabling a deeper understanding of the vibration modes of drug molecules in the low-frequency range. Moreover, this study demonstrates the sensitivity of terahertz time-domain spectroscopy (TDS) technology in detecting intermolecular hydrogen-bond interactions in drug cocrystals. When comparing cocrystal molecules with active pharmaceutical ingredient (API) molecules, it is found that cocrystals possess better binding energy, driven by intermolecular hydrogen bonds and dispersion forces.