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.