**5. Conclusions**

In this work, the solubility of florfenicol was determined by a gravimetric method in four binary solvents (methanol + water, ethanol + water, 1-propanol + water, and isopropanol + water) with temperatures from 278.15 to 318.15 K under atmospheric pressure. In these four mixed solvents, the solubility of florfenicol increased with the increase in temperature. At the same temperature, the solubility of florfenicol increases with the decrease in the water ratio in the methanol + water mixture solvent. While the solubility of florfenicol increases first and then decreases with the decrease in the ratio of water in ethanol + water, 1-propanol + water, and isopropanol + water mixture solvent, indicating a cosolvency phenomenon occurs in these three binary solvents. In this study, the modified Apelblat model, the CNIBS/R-K model, the Jouyban–Acree model, and the NRTL model were used to correlate the solubility data of florfenicol in four binary solvents. The RMSD values of each model show that the calculated solubility data are in good agreement with the experimental data for all four models, among which the CNIBS/R-K model provides the best fitting result. Most of the previous solubility articles only determined the solubility of florfenicol in pure solvents, and rarely determined the solubility of florfenicol in binary solvents. However, considering the solubilization requirements of florfenicol, especially in the research of preparing nanocrystals by antisolvent crystallization, the solubility data of florfenicol in binary solvents are highly desirable. The four alcohols involved in this study are the most commonly used organic solvents in experimental research and industry, in which Florfenicol has good solubility, so alcohol solvent can be used as an effective proper solvent. Needless to say, water is the most suitable antisolvent for florfenicol. Therefore, the solubility data obtained by this study can be used as fundamental data for research on the florfenicol nanocrystal preparation to achieve florfenicol solubilization.

**Author Contributions:** Data curation, X.Z. and P.C.; Resources, Q.Y.; Supervision, L.Z.; Writing original draft, X.Z.; Writing—review and editing, P.C., Q.Y. and L.Z. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by (Tianjin Municipal Natural Science Foundation) grant number [21JCYBJC00600].

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

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** The authors are grateful for the financial support of the Tianjin Municipal Natural Science Foundation (No. 21JCYBJC00600).

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