Spectroscopic analysis of the influence of various external factors on ethenzamide-glutaric acid (1:1) cocrystal formation.

Cocrystal formation may affect manufacturability (flow, compaction and processability) as well as solubility/dissolution, hygroscopicity and stability properties of drugs. Therefore, cocrystallization could be used to improve the pharmaceutical properties of low-soluble drugs such as ethenzamide. In this project, solid-state nuclear magnetic resonance and Fourier transform infrared spectroscopy studies were performed for ethenzamide-glutaric acid to obtain more information about the ethenzamide cocrystallization process. The impact of the grinding time of the physical mixture (ethenzamide-glutaric acid) on cocrystal formation and the further spontaneous cocrystallization was evaluated using spectroscopic methods and curve-fitting analysis of the spectra. The influence of pressure on the yield of cocrystal formation was also described. Additionally, studies on the effect of magic-angle spinning during solid-state nuclear magnetic resonance spectra collection on the initiation of cocrystal formation, have been performed. Based on this research, conclusions regarding the influence of the different external factors, such as pressure during the tableting process and grinding time, on the cocrystal formation have been drawn for ethenzamide cocrystals.