**4. Conclusions**

In conclusion, we have described three new pharmaceutical multicomponent crystals containing DIC and nucleobases (ADE, CYT, and ICT) as coformers. Expected heterosynthons assist formation of the new solid forms, disrupting the robust acid:acid dimmer synthon observed in reported DIC polymorphs. All solids consist of alternated layered structures connected by hydrogen bonds. This supramolecular organization confers good thermal stability, and good stability under accelerated ageing conditions and seems to have an important role in the dissolution properties of the solids. Relevant insights are inferred from the BFDH calculations where CYT and ICT, containing solids, possess a large crystal surface that expose hydrogen donor and acceptor groups, which interact with the water molecules of the bulk solvent.

**Supplementary Materials:** The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/cryst12081038/s1, Figure S1. PXRD patterns of the LAG screening experiments with the coformers of Table 2; Figure S2. PXRD patterns of DIC—ADE, DIC—CYT, and DIC—ICT after neat grinding; Figure S3. PXRD patterns of DIC—ADE, DIC—CYT, and DIC—ICT after LAG in methanol using different stoichiometries; Figure S4. Experimental PXRD pattern of DIC—ADE, DIC—CYT, and DIC—ICT, compared with DIC, coformers, and the corresponding calculated powder patterns; Figure S5. TGA traces of DIC–ADE (top), DIC—CYT (middle), and DIC–ICT (bottom); Figure S6. PXRD patterns of DIC–ADE (top), DIC—CYT (middle), and DIC–ICT (bottom) with respect to the stability under accelerated ageing conditions (40 ◦C, 75% RH) at different time intervals; Figure S7. PXRD patterns of DIC–ADE (top), DIC—CYT (middle), and DIC–ICT (bottom) after the stability slurry assay (at 25 ◦C, during 24 h, in water); Figure S8. Overlapping UV spectra of diclofenac (DIC) and nucleobase coformers (ADE: adenine, CYT: cytosine, ICT: isocytosine); Figure S9. ORTEP representation showing the asymmetric unit of DIC—ADE with an atom numbering scheme (thermal ellipsoids are plotted with the 50% probability level); Figure S10. ORTEP representation showing the asymmetric unit of DIC—CYT with atom numbering scheme (thermal ellipsoids are plotted with the 50% probability level); Figure S11. ORTEP representation showing the asymmetric unit of DIC—ICT with atom numbering scheme (thermal ellipsoids are plotted with the 50% probability level); Table S1. Results of the LAG experiments between DIC and selected coformers; Table S2. Hydrogen bonds for DIC—ADE [Å and deg.]; Table S3. Hydrogen bonds for DIC—CYT [Å and deg.]; Table S4. Hydrogen bonds for DIC—ICT [Å and deg.].

**Author Contributions:** Conceptualization and methodology, D.C.-L.; formal analysis and investigation, C.A.-P., F.J.A.-M., H.M.B.-R., J.N.-G., A.D.-M.; writing—original draft preparation, D.C.-L., F.J.A.-M.; writing—review and editing, D.C.-L.; funding acquisition, A.D.-M. and D.C.-L.; supervision, D.C.-L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Spanish Agencia Estatal de Investigación of the Ministerio de Ciencia, Innovación y Universidades (MICIU) and co-funded with FEDER, UE, project no. PGC2018- 102047-B-I00 (MCIU/AEI/FEDER, UE) and project B-FQM-478-UGR20 (FEDER-Universidad de Granada, Spain).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** F.J.A.-M. acknowledges an FPI grant (ref. PRE2019-088832).

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