RS, S (+) - and R (-)-ibuprofen cocrystal polymorphs: Vibrational spectra, XRD measurement and DFT calculation studies.

In this paper, cocrystal polymorphs of RS-ibuprofen (RS-IBU), S (+)-ibuprofen (S(+)-IBU), R (-)-ibuprofen (R(-)-IBU) with nicotinamide (NIC) were synthesized by different methods. RS-IBU is a chiral drug with only one chiral center in the molecule, which has two enantiomers (S (+)-IBU and R (-)-IBU). Due to the low solubility and bioavailability of IBU, its application is limited. The pharmaceutical cocrystal technology can improve the physicochemical properties of the drug. In this paper, we characterized RS-IBU, S (+)-IBU, R (-)-IBU, NIC, physical mixtures and cocrystal polymorphs by terahertz (THz), Raman and X-ray Diffraction (XRD), respectively. By observing the experimental results, we could clearly distinguish the cocrystal polymorphs. We found that the melt recrystallization method can generate cocrystal form A, while the solvent drop grinding method and solution evaporation method can generate cocrystal form B. In addition, in order to verify the successful preparation of them, we used density functional theory (DFT) to optimize and simulate the theoretical structures of the RS-IBU: NIC cocrystal polymorphs, and compared the simulated results with the experimental results. These research results provide a reference for the analysis and preparation of pharmaceutical cocrystal polymorphs and help to distinguish the cocrystal polymorphs.