Eutectic Itraconazole and Posaconazole System and the Advantages of Its Use in the Amorphous Form

Itraconazole (ITR) and posaconazole (POS) exhibit closely related molecular structures but differ significantly in their ability to form liquid crystalline (LC) phases. This makes them an attractive model system to investigate how subtle structural differences influence molecular organization in the amorphous state. In this work, we investigate coamorphous systems composed of ITR and POS prepared via melt-quenching, focusing on the interplay between molecular dynamics, physical stability, and LC ordering. Differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS) reveal that the glass transition temperature remains nearly unchanged over a wide compositional range, indicating comparable molecular mobility of all investigated systems. Despite this similarity, a pronounced, nonmonotonic dependence of crystallization kinetics on composition is observed, with a clear stability maximum at the eutectic ratio. Strikingly, this specific composition is also associated with the complete disappearance of the LC ordering characteristic of neat ITR. While ITR-rich mixtures close to the eutectic point still exhibit residual LC transitions, the eutectic composition yields a fully disordered amorphous phase. These results demonstrate, for the first time, that coamorphization at the eutectic composition might suppress LC ordering. The findings highlight the critical role of composition in governing both molecular organization and stability in amorphous pharmaceuticals.