Coamorphous drug formulations are a promising approach to improve solubility and bioavailability of poorly watersoluble drugs. On the basis of theoretical assumptions involving molecular interactions, the 1:1 molar ratio of drug and coformer is frequently used as "the optimal ratio" for a homogeneous coamorphous system (i.e., the coamorphous system with the highest physical stability and, if strong interaction is possible between two molecules, the highest glass transition temperature (T g )). In order to more closely investigate this assumption, L-aspartic acid (ASP) and L-glutamic acid (GLU) were investigated as coformers for the basic drug carvedilol (CAR) at varying molar ratios. Salt formation between CAR with ASP or GLU was expected to occur at the molar 1:1 ratio based on their chemical structures. Interestingly, the largest deviation between the experimental T g and the theoretical T g based on the Gordon−Taylor equation was observed at a molar ratio of around 1:1.5 in CAR−ASP and CAR−GLU systems. In order to determine the exact value of the ratio with the highest T g , a data fitting approach was established on thermometric data of various CAR−ASP and CAR−GLU systems. The highest T g was found to be at CAR−ASP 1:1.46 and CAR− GLU 1:1.43 mathematically. Spectroscopic investigations and physical stability measurements further confirmed that the optimal molar ratio for obtaining a homogeneous system and the highest stability can be found at a molar ratio around 1:1.5. Overall, this study developed a novel approach to determine the optimal ratio between drug and coformers and revealed the influence of varying molar ratios on molecular interactions and physical stability in coamorphous systems.

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This study clarified the interaction mechanism and structural characteristics of ternary complexes of β-lactoglobulin, curcumin, and fatty acids.