Pharmaceutical Cocrystals of Nicorandil with Enhanced Chemical Stability and Sustained Release

Nicorandil (NCD) is a chemically unstable drug and sensitive to humidity, heat, and mechanical stress in manufacturing processes. In this work, the cocrystals of NCD with organic acids were designed and synthesized to enhance the stability of NCD. Cocrystals of NCD with 1-hydroxy-2-naphthoic acid, salicylic acid, 3-hydroxybenzoic acid, and 2,5-dihydroxybenzoic acid were obtained. Hydrothermal stability study showed that cocrystals performed with remarkable stability advantages compared with pure NCD. On the basis of mechanism research, the stability improvements of NCD molecules can be attributed to the realignments of NCD molecules in cocrystals. After the formation of cocrystals, the novel packing styles of NCD break the self-catalyzed decomposition process in pure NCD structure. Moreover, intrinsic dissolution rate characterizations showed that the formation of cocrystals could also optimize the dissolution behavior of NCD to realize the objective of sustained release.