Mechanochemical synthesis of brexpiprazole cocrystals to improve its pharmaceutical attributes

Abstract

In the present study, cocrystallization of a new piprazole analogue drug, brexpiprazole (BREX), with coformers such as succinic acid and catechol was carried out using ball milling to address the poor solubility and dissolution rate of the molecule. Before initiating cocrystallization, several ball milling process parameters, including milling time, ball size and RPM were optimized to obtain the cocrystals with the highest purity and yield. The cocrystals generated using the optimized ball milling process were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage microscopy, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. Equilibrium solubility and dissolution studies on the cocrystals were performed in 0.05 M acetate buffer, pH 4.3. Nearly 2.5 fold enhancements in the equilibrium solubility and dissolution rate have been observed with the cocrystals compared to plain BREX and its physical mixture with the coformers.