Near-infrared spectroscopy-based nondestructive at-line analysis of physicochemical properties of atorvastatin calcium hydrate after grinding

The purpose of this study was to monitor the physicochemical properties of atorvastatin calcium sesquihydrate (ATC) ground products during grinding and to explore the polymorphous formation caused by intermolecular interactions. Changes in physicochemical properties, such as the surface adsorbed and channel water content (AW), lattice water content (BW), crystallinity (XRD%), and apparent solubility (Cs), of the ground products during grinding were evaluated via X-ray diffractometry, thermogravimetry, near-infrared (NIR) spectroscopy, and initial dissolution kinetic methods. Partial least-squares regression calibration models were created using NIR spectroscopy, to predict the physicochemical properties. The molecular behaviors of these models were analyzed using regression vectors. Changes in the physicochemical properties of the ground products during grinding were caused by the transformation of BW into AW by mechanical energy, where crystalline ATC was transformed into an amorphous solid. The Cs of the ground products increased significantly with increasing grinding time. Based on the NIR spectroscopy results, the amorphous transition of the crystals induced during grinding was caused by the cleavage of intermolecular interactions. Furthermore, over longer grinding times, the polymorphic transitions of amorphous solids to highly soluble amorphous solids were caused by the cleavage of intramolecular interactions between ATC and water in the amorphous ATC complex. [Display omitted] •Polyamorphious atorvastatin calcium prepared by dry-grinding.•Near-infrared spectroscopy detects both intermolecular and intramolecular interactions.•Physicochemical properties associate with hydration manner.•Physicochemical properties evaluate using near-infrared spectroscopy.