*3.2. Mechanochemical Synthesis*

Liquid-Assisted Grinding is a versatile and efficient methodology widely used to obtain pharmaceutical multicomponent solid forms [42]. A screening through LAG was conducted with DIC and all coformers listed in Table 2. Unfortunately, despite the promising results obtained by the COSMOQuick analysis, only those LAG synthesis with the coformers ADE, CYT, and ICT were successful and achieved new phases whilst the other coformers yielded only physical mixtures of the two components. The product of these reactions was characterized by PXRD and compared with the X-ray powder pattern of the parent components (Table S1, Figure S1). Only experiments using ADE, CYT, and ICT as coformers provided a new PXRD pattern and were used for subsequent characterization (Figure 1). After the screening procedure, the work was focused on the search for finetuning conditions to obtain multicomponent materials of DIC with ADE, CYT, and ICT. Neat grinding experiments resulted in physical mixtures of the components (Figure S1). Neat grinding approach only led to physical mixtures (Figure S2). It is reported that this synthesis technique sometimes yields products with low crystallinity, partial reactions, or not even a reaction at all [43]. However, it is well known that adding small amounts of liquids accelerate the reaction, which essentially drove us to the idea of using LAG synthesis instead. LAG experiments were then performed using methanol and different stoichiometries (1:1, 1:2, and 2:1) (Figure S3). A new common pattern was observed in the three stoichiometries. However, in the 1:2 and 2:1 ratios, there were also peaks corresponding to the coformer and DIC, respectively. Only the 1:1 ratio provided unique different PXRD patterns. Comparing these patterns with those simulated from the crystal structures confirmed the monophasic nature of the bulk solids (Figure S4).

**Figure 1.** PXRD patterns of DIC, DIC–ADE, DIC–CYT, and DIC–ICT obtained by Liquid-Assisted Grinding (LAG) with methanol in a 1:1 ratio.
