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 R 2 2 (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 .