**Differential Scanning Calorimetry (DSC) Analysis**

DSC is one essential technique to characterize the solid phase behavior of a material and mixtures. It is crucial to detect the eutectic nature of a multicomponent system as typically the melting point of the eutectic mixture is lower than either of the parent components and the eutectic melting can be identified via the melting events occurring. The DSC patterns of the various AMG-coformer mixtures overlayed with those of the pure components are shown in Figure 3, specifically for the AMG-CAF system in Figure 3a, the AMG-NIC system in Figure 3b and the AMG-ZMD system in Figure 3c.

**Figure 3.** DSC patterns of the different AMG-coformer compositions showing the melting point depressions and the eutectic peak, (**a**) AMG and CAF, (**b**) AMG and NIC, and (**c**) AMG and ZMD.

The thermogram of AMG exhibits only one endothermic melting peak, suggesting no polymorphic transition during the heating cycle. The eutectic melting peak for the AMG-NIC system (Figure 3b) is found at 99.2 ◦C, being, as expected, significantly lower than for both the starting materials. A close-to single eutectic peak is observed for the ~50% mixture, indicating the presence of the "purely" eutectic phase and thus, the eutectic composition in the AMG-NIC system. In the case of the AMG-CAF system at different weight% ratios, except at the eutectic composition, DSC curves exhibited three endothermic transition effects (see Figure 3a). The first endothermic peak signifies the eutectic temperature, whereas another endotherm signifies the melting of excess AMG or CAF, respectively. The supplementary peak observed at 137.7 ◦C corresponds to the enantiotropic phase transition of caffeine polymorphic form II to form I [25,26]. The eutectic composition is found to be

close to 75 wt.% AMG composition. For the AMG-ZMD system, the melting endothermic peak at 101.8 ◦C refers to the eutectic melting (see Figure 3c), while the eutectic composition is found close to the AMG-ZMD composition of ~50 wt.%. Table 1 contains the measured temperatures and enthalpies of melting for the pure AMG, the coformers used and their eutectic mixtures. Hot stage microscopic analysis results of the eutectic mixtures which are presented in Figure S1 (Supporting Information), also support the eutectic nature of the AMG mixtures exhibiting a uniform melting in a narrow temperature range.

**Table 1.** Melting point (M.P) and melting enthalpy (M.E) of drug AMG, the coformers and their eutectic compositions.

