MCR-ALS analysis of IR spectroscopy and XRD for the investigation of ibuprofen - nicotinamide cocrystal formation

To improve aqueous solubility, a poorly water-soluble active ingredient is classically combined with a conformer to form cocrystals. Hot melt extrusion is one preparation method for the formation of cocrystal solids. The aim of our study was to determine the optimal temperature conditions for the formation of ibuprofen and nicotinamide cocrystals using real-time infrared (IR) and X-ray diffraction (XRD) measurements. IR spectra and XRD patterns were subjected to multivariate curve resolution alternating least squares (MCR-ALS) analysis and decomposed into several components. Each component was descriptive of a specific step in the formation of the cocrystal. Cocrystal formation was followed by a separation phase between amorphous ibuprofen and crystalline nicotinamide. Our results suggest that, when using the hot melt exclusion method, careful consideration should be made towards optimizing processing temperatures in order to prevent amorphization and promote control over the process of cocrystal formation. [Display omitted] •Monitoring of cocrystallization process between ibuprofen and nicotinamide•Decomposition of IR spectra and XRD during the cocrystallization by MCR-ALS•Optimization of the processing temperature for the cocrystallization