Studies on the synthesis, structural characterization, Hirshfeld analysis and stability of apovincamine (API) and its co-crystal (terephthalic acid: Apovincamine = 1:2)

Abstract

Apovincamine and the corresponding co-crystal have been synthesized and characterized by single crystal XRD, FT-IR, UV, TGA/DSG. Components of the crystalline phase have also been investigated in terms of their corresponding Hirshfeld surface. In the crystal lattice, a three-dimensional hydrogen-bonded network is observed in the co-crystal, including the formation of a two-dimensional molecular scaffold. Hirshfeld surfaces and fingerprint plots indicate that the structures are stabilized by H⋯H, C−H⋯π, C–H⋯O and O–H⋯N intermolecular interactions. In this work, the co-crystal strategy has been applied successfully to apovincamine. One important parameter, i.e. solubility in water, has also been significantly improved, which proves to be an important factor for bioavailability. Furthermore, DSC/TGA analysis indicates that the co-crystal maintains its crystallinity up to 200°C, suggesting a higher stability of the co-crystal compared to apovincamine.