Investigation of the Formation Process of Two Piracetam Cocrystals during Grinding

Cocrystal formation rates during dry grinding and liquid-assisted grinding were investigated by X-ray powder diffractometry and Raman spectroscopy. Two polymorphic forms of piracetam were used to prepare known piracetam cocrystals as model substances, i.e.,piracetam-citric acid and piracetam-tartaric acid cocrystals. Raman spectroscopy in combination with principal component analysis was used to visualize the cocrystal formation pathways. During dry grinding, cocrystal formation appeared to progress via an amorphous intermediate stage, which was more evident for the piracetam-citric acid than for the piracetam-tartaric acid cocrystal. It was shown that liquid-assisted grinding led to faster cocrystal formation than dry grinding, which may be explained by the higher transformation rate due to the presence of liquid. The cocrystal formation rate did not depend on the applied polymorphic form of the piracetam and no polymorphic cocrystals were obtained.