Molar Ratio-Dependent Crystallization in Coamorphous Celecoxib-Carbamazepine Systems: The Interplay of Thermodynamics and Kinetics.

Coamorphous drug delivery systems have emerged as a promising formulation strategy to enhance the solubility, oral bioavailability, and physical stability of poorly water-soluble drugs. The molar ratio of components in coamorphous systems plays a critical role in determining their physical stability. In this study, we investigated the crystallization behavior of coamorphous celecoxib-carbamazepine (CEL-CBZ) systems at different molar ratios. The growth rates of CEL crystals, CBZ crystals, and CEL-CBZ cocrystals were observed to exhibit distinct dependencies on the molar ratio of coamorphous systems, primarily due to their unique thermodynamic driving forces, despite sharing the same kinetic factor. The influence of the molar ratio on the crystallization of coamorphous systems arises from the interplay between its effects on molecular mobility and thermodynamic driving forces, leading to either cooperative or competing effects. Both the crystal growth and crystallization tendency results reveal that thermodynamics plays a more dominant role than kinetics in the crystallization of coamorphous CEL-CBZ systems across various molar ratios. This study provides fundamental insights into the mechanism by which the molar ratio influences the crystallization of coamorphous systems, highlighting the complex crystallization behavior of multicomponent amorphous systems as an interplay between kinetics and thermodynamics.