3.5.2. IDR Test

Given its kinetic nature, IDR assumes a better correlation with in vivo drug dissolution dynamics than solubility [34]. Thus, IDR studies were carried out at pH 1.2 in this work, and the results are summarized in Figure 10. The ARI held an IDR of 0.5051 mg·cm−2·min−1, while the IDR of the ARI-ADI salt, slightly lower than that of its acetone hemisolvate, significantly increased to 0.9263 mg·cm−2·min−<sup>1</sup> and was about twice as much as that of the ARI. Not unexpectedly, the IDR of the ARI-SAL salt was only 0.3745 mg·cm−2·min<sup>−</sup>1, significantly lower than that of the ARI.

These findings indicated that ARI-ADI salt and its acetone hemisolvate had predictable advantages in vivo absorption over ARI-SAL salt and the untreated ARI. This may be due to many causes. First, the relatively higher hygroscopicity and lower melting point may lead to easier dissolution in an aqueous solvent, because of it demanding less lattice energy to break. Molecular constituents were also one of the important causes. The CCF of ARI-ADI salt was more soluble than that of the ARI-SAL salt, and their solubility behaviors follow the rule of thumb that the greater solubility of the CCF, the more soluble the salt will be [18]. Finally, their spatial structures may also be associated with their differences in solubility. The ADI molecules linked with the solvent molecules to form a hydrophilic layer. As a result, water molecules permeate more easily into the layer stacking spatial structure and cause it to disintegrate in aqueous solvent.

**Figure 10.** Intrinsic dissolution profiles of the ARI and its crystal salts in hydrochloric acid buffer (pH 1.2).
