Enhancing the Hygroscopic Stability of S‑Oxiracetam via Pharmaceutical Cocrystals

Four cocrystals of (S-ox)­(ga) (1), (RS-ox)­(ga) (2), (S-ox)­(pa) (3), and (RS-ox)­(pa) (4) were prepared (S-ox = S-oxiracetam, RS-ox = racemic oxiracetam, ga = gallic acid, pa = 3,4-dihydroxybenzoic acid), and their structures were determined by single X-ray diffraction. In 1/2, two ga molecules link two S-ox/RS-ox molecules through intermolecular hydrogen bonds with a new R22(9) synthon to form a tetramer, the tetramers are further linked by intertetramer hydrogen bonds to generate a 2D sheet, and the adjacent 2D sheets are connected by intersheet hydrogen bonds to form the 3D structure of 1/2. In 3/4, the ox molecules form a 1D helical chain through intermolecular hydrogen bonds, and the helical chains are further linked by pa molecules through intermolecular hydrogen bonds to form a 2D sheet. The results of hygroscopic stability experiments indicate that the hygroscopic stability of S-ox is much enhanced after the formation of cocrystal 1.