**4. Conclusions**

Nefiracetam cocrystal screening led to the identification of 13 novel cocrystal systems. Among these, three biocompatible systems were identified (NCA, NOA, and NZC) and their physicochemical properties (stability, solubility, and dissolution) were evaluated and compared to those of the parent compound Nefiracetam. The zinc chloride ionic cocrystal showed an impressive improvement in thermal stability, but strongly reduced the solubility by about 90% in organic solvents in comparison with the parent drug. The use of dicarboxylic acid coformers can induce a complete different behavior, with citric acid improving the solubility, while oxalic acid reduces this latter when the cocrystal behaves congruently. For non-congruen<sup>t</sup> systems, the presence of the coformer always increases the overall solubility. All cocrystals, as well as the parent compound, are rapidly dissolving. Overall, this study confirms that cocrystallization can be used as an effective tool to impact the physico-chemical properties of a drug compound. A relevant choice in the coformer can either help improve formulation stability, or bioavailability of the drug. The coformer selection is of utter importance, as strong variations can occur depending on the nature of the selected coformer.

**Supplementary Materials:** The aforementioned content is available online at http://www.mdpi.com/1999-4923/ 12/7/653/s1. The coformer list (133) can be found in the Supplementary Materials. The full NCA, NOA, and NZC form screening and the humidity exposure (DVS) as well are presented in the Supplementary Materials. All the XRPD (experimental and simulated) and DSC data of the other positive hits (suspected and confirmed) mentioned in the manuscript are in the Supplementary Materials too. The crystallographic data and the specific refinement method related to each structure solved in this work are presented in the Supplementary Materials.

**Author Contributions:** Conceptualization, T.L. and X.B.; methodology, X.B.; software, K.R. and N.T.; validation, X.B.; formal analysis, X.B., K.R., N.T., and L.C.; investigation, X.B. and C.C.G.; resources, T.L. and J.W.; data curation, X.B., K.R., and N.T.; writing—original draft preparation, X.B.; writing—review and editing, X.B., T.L., J.W., and K.R.; visualization, X.B., T.L., J.W., and K.R., X.B.; supervision, T.L. and J.W.; project administration, T.L.; funding acquisition, T.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the "Fonds Européen de Développement <sup>R</sup>égional" and the "Région Wallonne" in the operational framework Wallonie-2020.EU (Tera4all).

**Conflicts of Interest:** The authors declare no conflict of interest.
