3.6.2. Intrinsic Dissolution Rate (IDR)

IDR analysis at pH 1.2 (Figure 11) revealed a di fferent behavior of the samples, with crystalline ITR showing the slowest IDR in comparison to FD ITR, which achieved the highest dissolution rate of all the samples analyzed. The faster IDR of the FD ITR in relation to ITR was related to the disordered state of the API in the former. As identified by the solid-state characterization (Figure S4), the API in FD ITR was in the liquid crystal mesophase, a higher energy form than the crystalline state of ITR (the starting material). Therefore, the high free energy of FD ITR promoted the quicker dissolution of the API [10,37]. A one-way ANOVA revealed that the investigated samples had statistically di fferent IDR values, except for crystalline ITR and the ITR–TER cocrystal. In this case, cocrystallisation was unable to improve the dissolution rate of the API, likely due to the poor aqueous solubility of the coformer, TER, which has an aqueous solubility of 17 μg/mL at 25 ◦C [38]. This value is low, but still much higher than ITR's solubility in water of around 1 ng/mL [39]. The influence of the coformer on the IDR values was evident for the other cocrystals, as the rank order of the aqueous solubility of pure coformers was OXA > SUC > TER (OXA: 130–140 mg/mL [40] and SUC: 83 mg/mL [41]), following the rank order of the IDR values of the equivalent cocrystals: ITR–OXA > ITR–SUC > ITR–TER (Figure 11). Raman spectroscopy of the disks post IDR studies showed the conservation of their solid-state characteristics.

**Figure 11.** Intrinsic dissolution rates (IDRs) of: ITR starting material powder (ITR), freeze dried ITR (FD ITR), the ITR–OXA cocrystal, ITR–SUC cocrystal and ITR–TER cocrystal.
