In order to shed light on the disso

In order to shed light on the dissolution course, oversaturation profiles of the cocrystal versus an equimolar blend of the individual materials are tested, and the results are illustrated in Fig. 7. As shown in Fig. 7a, in the case of parent SYA, a maximum concentration of 29.02 mM was achieved at 3 h, and then the steady-state plateau concentrations were maintained until the end of the experiment (40 h). While for the cocrystal, the peak was reached in 0.5 h, earlier than that of parent SYA, and the peak concentration of 336.13 mM observed for the cocrystal was amazing 11.6-fold higher than that obtained with parent SYA. Meanwhile, it is worth noting that the concentration of SYA from the cocrystal was still 5.2 times than that of parent SYA at 2 h, showing a relatively long oversaturation duration. On the other hand, as illustrated in Fig. 7b, the INH content in the cocrystal has no saturation effect, a result expected for its high solubility. The optimized dissolution behavior of the cocrystal could be explained from the cocrystal structural point of view. On the cocrystal solid being exposed to the water environment, the highly polar INH molecules in INH-SYA cocrystal release rapidly into the medium from the lattice of the cocrystal. While the remaining framework of SYA suspends in the water solution with a weak self-aggregation state. The amorphous-like state of SYA may dissipate in the solution quickly, leading to the improved dissolution behavior of SYA [30]. In a word, the dissolution properties of SYA in the cocrystal was effectively improved due to the superior water solubility of INH, which will lay the foundation for the improvements of bioavailability and hepatoprotective effect of SYA. 3.3. In vivo pharmacokinetics studies