*4.2. Solubility Data*

The experimental and calculated molar ratio solubility of florfenicol in binary solvents of methanol + water, ethanol + water, 1-propanol + water, and isopropanol + water is listed in Tables 1–4, and are plotted in Figures 4–7.

The experimental results show that at constant solvent composition, the solubility of florfenicol in all four binary solvent mixtures increases with increasing temperature. Moreover, at the same temperature, the proportion of water in the binary solvent has a great influence on the solubility of florfenicol. 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 binary solvent, indicating a cosolvency phenomenon occurs in these three binary solvents. The peak position of the maximum solubility of florfenicol slightly shifted from 0.9 to 0.7 with the increase in the experimental temperature. While the solubility of florfenicol in methanol + water mixed solvent increases with the decrease in water ratio and there was no obvious cosolvency phenomenon. Furthermore, at the same

temperature and mass fraction of water, the solubility of florfenicol in the tested solvent systems follows the order: (ethanol + water) > (1-propanol + water) > (isopropanol + water), which is the same as the order of the polarity of alcohol. Considering that florfenicol is a polar molecule, the effect of binary solvent mixtures on the solubility can be explained by the 'Similar Dissolution Rule'.

**Table 1.** Experimental and calculated molar ratio solubility of florfenicol in binary solvent mixtures of methanol + water from *T* = 278.15 to 318.15 K.


**Table 1.** *Cont.*



**Table 1.** *Cont.*

<sup>a</sup> *ω*<sup>A</sup> represents the mass fraction of alcohols (methanol, ethanol, 1-propanol, or isopropanol) in binary solvent mixtures; *x*<sup>F</sup> exp is the experimental mole fraction solubility of florfenicol in the binary solvents; *x*<sup>F</sup> cal, Apel, *x*<sup>F</sup> cal, RK, *x*F cal, JA, and *x*<sup>F</sup> cal, NRTL are the mole fraction solubility calculated by Equations (2), (4), (6), and (10), respectively. <sup>b</sup> The standard uncertainty of temperature is *uc(T)* = 0.1 K. The relative standard uncertainty of pressure is *ur(P)* = 0.05. The relative standard uncertainty of binary solvent composition and solubility measurement is *ur*(*ω*A) = 0.002 and *ur(x*F*)* = 0.05.

**Table 2.** Experimental and calculated molar ratio solubility of florfenicol in binary solvent mixtures of ethanol + water from *T* = 278.15 to 318.15 K.


**Table 2.** *Cont.*


**Table 2.** *Cont.*


<sup>a</sup> *ω*<sup>A</sup> represents the mass fraction of alcohols (methanol, ethanol, 1-propanol, or isopropanol) in binary solvent mixtures; *x*<sup>F</sup> exp is the experimental mole fraction solubility of florfenicol in the binary solvents; *x*<sup>F</sup> cal, Apel, *x*<sup>F</sup> cal, RK, *x*F cal, JA, and *x*<sup>F</sup> cal, NRTL are the mole fraction solubility calculated by Equations (2), (4), (6) and (10), respectively. <sup>b</sup> The standard uncertainty of temperature is *uc(T)* = 0.1 K. The relative standard uncertainty of pressure is *ur(P)* = 0.05. The relative standard uncertainty of binary solvent composition and solubility measurement is *ur*(*ω*A) = 0.002 and *ur(x*F*)* = 0.05.


**Table 3.** Experimental and calculated molar ratio solubility of florfenicol in binary solvent mixtures of 1-propanol + water from *T* = 278.15 to 318.15 K.

**Table 3.** *Cont.*



**Table 3.** *Cont.*

<sup>a</sup> *ω*<sup>A</sup> represents the mass fraction of alcohols (methanol, ethanol, 1-propanol, or isopropanol) in binary solvent mixtures; *x*<sup>F</sup> exp is the experimental mole fraction solubility of florfenicol in the binary solvents; *x*<sup>F</sup> cal, Apel, *x*<sup>F</sup> cal, RK, *x*F cal, JA, and *x*<sup>F</sup> cal, NRTL are the mole fraction solubility calculated by Equations (2), (4), (6), and (10), respectively. <sup>b</sup> The standard uncertainty of temperature is *uc(T)* = 0.1 K. The relative standard uncertainty of pressure is *ur(P)* = 0.05. The relative standard uncertainty of binary solvent composition and solubility measurement is *ur*(*ω*A) = 0.002 and *ur(x*F*)* = 0.05.

**Table 4.** Experimental and calculated molar ratio solubility of florfenicol in binary solvent mixtures of isopropanol + water from *T* = 278.15 to 318.15 K.


**Table 4.** *Cont.*


**Table 4.** *Cont.*


<sup>a</sup> *ω*<sup>A</sup> represents the mass fraction of alcohols (methanol, ethanol, 1-propanol, or isopropanol) in binary solvent mixtures; *x*<sup>F</sup> exp is the experimental mole fraction solubility of florfenicol in the binary solvents; *x*<sup>F</sup> cal, Apel, *x*<sup>F</sup> cal, RK, *x*F cal, JA, and *x*<sup>F</sup> cal, NRTL are the mole fraction solubility calculated by Equations (2), (4), (6), and (10), respectively. <sup>b</sup> The standard uncertainty of temperature is *uc(T)* = 0.1 K. The relative standard uncertainty of pressure is *ur(P)* = 0.05. The relative standard uncertainty of binary solvent composition and solubility measurement is *ur*(*ω*A) = 0.002 and *ur(x*F*)* = 0.05.

**Figure 4.** Molar ratio solubility data of florfenicol in methanol + water binary solvents at *T* = 278.15 K to 318.15 K.

**Figure 5.** Molar ratio solubility data of florfenicol in ethanol + water binary solvents at *T* = 278.15 K to 318.15 K.

**Figure 6.** Molar ratio solubility data of florfenicol in 1-propanol + water binary solvents at *T* = 278.15 K to 318.15 K.

**Figure 7.** Molar ratio solubility data of florfenicol in isopropanol + water binary solvents at *T* = 278.15 K to 318.15 K.

### *4.3. Data Correlation*

The experimental solubility data in this work were correlated by the modified Apelblat model, the CNIBS/R-K model, the Jouyban–Acree model, and the NRTL model. Rootmean-square deviations (RMSD) were used to evaluate the accuracy and applicability of these models. It is defined as follows:

$$\text{RMSSD} = \sqrt{\frac{1}{N} \sum\_{j=1}^{N} \left( \boldsymbol{\omega}\_{j}^{\text{cal}} - \boldsymbol{\omega}\_{j}^{\text{exp}} \right)^{2}} \tag{11}$$

where *N* stands for the total number of experiments, *xj* exp refers to the experimental mole fraction solubility, and *xj* cal refers to the calculated mole fraction solubility of florfenicol.

The model parameters and RMSD values are listed in Tables 5–8. The RMSD values obtained by the modified Apelblat model, the Jouyban–Acree model, and the NRTL model are less than 0.001. The RMSD values obtained by the CNIBS/R-K model are less than 0.00001, indicating that the calculated solubility data of the CNIBS/R-K model is in best agreement with the experimental data.

**Table 5.** Model parameters of modified Apelblat model for molar ratio solubility of florfenicol in binary solvents.



**Table 5.** *Cont.*

**Table 6.** Model parameters of CNIBS/R-K model for molar ratio solubility of florfenicol in binary solvents.


**Table 6.** *Cont.*


**Table 7.** Model parameters of Jouyban–Acree model for molar ratio solubility of florfenicol in binary solvents.



**Table 7.** *Cont.*

**Table 8.** Model parameters of NRTL model for molar ratio solubility of florfenicol in binary solvents.

