Relaxation Polyamorphism of Rosuvastatin and Physicochemical Characterisation of a Rosuvastatin-Carvedilol Co-Amorphous System.

Objective: In this study, the solid-state properties of two amorphous forms of rosuvastatin calcium (ROS) and co-amorphous systems of rosuvastatin with carvedilol (CAR) were investigated. Methods: The studied systems were investigated using TGA, DSC, TMDSC, PXRD, SAXS, SSNMR, and DVS. Results: DSC, TMDSC and SAXS revealed subtle differences between as-received ROS (ROS AR) and freshly prepared amorphous ROS (ROS AM), providing evidence of relaxation polyamorphism. Analysis of the scanning-rate dependence of the glass transition temperature classified ROS as a fragile glass former. Water sorption studies of ROS AR using Brunauer-Emmett-Teller analysis, the Guggenheim-Anderson-de Boer equation, and Young-Nelson models indicated a moderate specific surface area and multilayer adsorption, with water binding both at the surface and within the bulk. Co-amorphous CAR-ROS systems in various molar ratios exhibited single glass transitions, confirming the formation of homogenous amorphous phases. Negative deviations from the Couchman-Karasz equation indicated non-ideal mixing behaviour. Physical ageing studies showed high stability of the ROS AM and CAR-ROS 1:1 co-amorphous system, which remained amorphous after three years of storage. Conclusions: Overall, ROS forms stable amorphous and co-amorphous systems with CAR, exhibiting favourable miscibility, structural stability, and potential for application in fixed-dose combination formulations.