Measurement and Correlation of Solubility of Gatifloxacin in 12 Pure

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Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Measurement and Correlation of Solubility of Gatifloxacin in 12 Pure Solvents from 273.15 K to 318.15 K Renjie Xu† and Jian Wang*,‡ †

Guangling College, Yangzhou University, YangZhou, Jiangsu 225009, P. R. China College of Chemistry & Chemical Engineering, YangZhou University, YangZhou, Jiangsu 225002, P. R. China

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‡

ABSTRACT: The solubility of gatifloxacin in 12 pure organic solvents (methanol, ethanol, n-propanol, n-butanol, isopropanol, acetone, butanone, acetonitrile, 1,4-dioxane, ethyl acetate, toluene, and N,N-dimethylformamide (DMF)) was obtained at temperatures from 273.15 K to 318.15 K. The results show that the solubility of gatifloxacin in those 12 pure solvents increases with increasing temperature. At a given temperature range, they gradually decrease in the following order: ethyl acetate (6.789 × 10−3, 298.15 K) > DMF (5.657 × 10−3, 298.15 K) > butanone (3.488 × 10−3, 298.15 K) > acetonitrile (2.811 × 10−3, 298.15 K) > n-butanol (2.246 × 10−3, 298.15 K) > acetone (1.766 × 10−3, 298.15 K) > 1,4-dioxane (1.288 × 10−3, 298.15 K) > n-propanol (0.922 × 10−3, 298.15 K) > ethanol (0.698 × 10−3, 298.15 K) > methanol (0.531 × 10−3, 298.15 K) > isopropanol (0.401 × 10−3, 298.15 K) > toluene (0.261 × 10−3, 298.15 K). The (KAT-LSER) model was applied to analyze the effect of the solute−solvent intermolecular interactions on the solubility in those pure solvents. Moreover, the obtained solubility data were correlated with the modified Apelblat equation and the λh equation. Between the experimental and calculated solubility data, the largest value of relative average deviations (RAD) was 0.77 × 10−2, and it is 0.15 × 10−4 for rootmean-square deviations (RMSDs). The results showed that the experimental values are in good agreement with the calculated values. The experimental solubility and the models in this study could be helpful in applications in the field of medicine.

1. INTRODUCTION Fluoroquinolones are antibacterial drugs for the treatment of human and animal infections in the world. The pharmacological mechanism of fluoroquinolones involves binding with topoisomerase IV and cyclotransferase in the presence of DNA, resulting in the formation of protein conformational change. Gatifloxacin (Figure 1; C19H22FN3O4 and CAS registry

past few decades, gatifloxacin has been used to treat uncomplicated and complicated urethral and cervical gonococcal infections, acute sinusitis, urinary tract infections and pyelonephritis, community-acquired pneumonia, and acute exacerbations of chronic bronchitis.4 At present, gatifloxacin is also used as an eye drop formulation. Various processes have been proposed to prepare gatifloxacin; in general, gatifloxacin was prepared from 3-methoxy-2,4,5-trifluoro benzoic acid by acylchorination, condensed with diethylmalonate, partial hydrolysis and decarboxylation, condensed with triethylorthoformate, cyclopropylamine displacement, cyclization, reacted with triacyloxyborate, and condensed with 2-methylpiperazine and then hydrosis.5−9 Many studies have focused on the synthesis of gatifloxacin, but only a few have attempted to establish a solid−liquid equilibrium phase diagram for preparation of pharmaceutical preparations. In order to provide the fundamental basis for preparation of gatifloxacin pharmaceutical preparations, knowledge of solubility for gatifloxacin in different solvents is needed. Because gatifloxacin is widely used in the field of medicine, the requirement of product purity is getting higher and higher. In the present work, by using the isothermal saturation method,10−12 the solubility data of gatifloxacin in 12 organic solvents

Figure 1. Chemical structure of gatifloxacin.

number: 112811-59-3) is a synthetic antimicrobial agent of the fluoroquinolone family. It showed enhanced activity against atypical agents including penicillin-sensitive and penicillinresistant Staphylococcus pneumoniae, some anaerobes, and Gram-positive bacteria.1,2 Because gatifloxacin has a good absorption rate in the gastrointestinal tract, it can be used orally or intravenously, and the oral utilization rate is about 96%.2,3 In the © XXXX American Chemical Society

Received: October 8, 2018 Accepted: December 26, 2018

A

DOI: 10.1021/acs.jced.8b00902 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Source and Properties of Gatifloxacin and the Selected Solvents chemicals

molar mass (g·mol−1)

CAS number

source

gatifloxacin methanol n-propanol ethanol n-butanol isopropanol acetone butanone acetonitrile ethyl acetate 1,4-dioxane toluene N,N-dimethylformamide

151.12 32.04 60.10 46.07 74.12 60.10 58.08 72.11 41.05 88.11 88.11 92.14 73.09

112811-59-3 67-56-1 71-23-8 64-17-5 71-36-3 67-63-0 67-64-1 78-93-3 75-05-8 141-78-6 123-91-1 108-88-3 68-12-2

Wuhan Dahua Pharmaceutical Co., Ltd. (China)

Sinopharm Chemical Reagent Co., Ltd., China

final mass fraction purity

analytical method

0.997 0.995 0.996 0.995 0.995 0.994 0.996 0.994 0.995 0.995 0.996 0.995 0.996

HPLCa GCb GC GC GC GC GC GC GC GC GC GC GC

a

High-performance liquid-phase chromatograph. bGas chromatography.

(methanol, ethanol, n-propanol, n-butanol, isopropanol, acetone, 1,4-dioxane, toluene, butanone, acetonitrile, ethyl acetate, and DMF) were researched at T = 273.15 to 318.15 K and P = 101.3 kPa. The solubility values obtained were correlated with the modified Apelblat equation and the λh equation. The (KAT-LSER) model was applied to analyze the effect of the solute−solvent intermolecular interactions on the solubility in those pure solvents. The obtained solubility data will be important in the preparation of pharmaceutical dosage forms.

2. THERMODYNAMIC AND CORRELATING MODELS In order to correlate and expound the shape of the solubility profile for gatifloxacin in the selected 12 solvents, we applied two thermodynamic models to correlate and compute the experimental result, which are the modified Apelblat equation13,14 and the λh equation,15,16 respectively. 2.1. Modified Apelblat Equation. The modified Apelblat equation is a function of the mole fraction solubility and absolute temperature T. As expressed in eq 1, it is a semiempirical equation13,14 B ln x = A + + C ln(T /K) T /K

Figure 2. XRD patterns of gatifloxacin raw material and the solids crystallized in pure solvents.

chromatograph) was obtained from Dahua Pharmaceutical Company (Wuhan, China). All solvents (mass fraction purities were all greater than 0.994, which were tested by gas chromatography) were purchased from Sinopharm Chemical Reagent Company (China). All chemical compounds were used as received without additional purification, and Table 1 presents their detailed information. 3.2. Solubility Determination. In the present work, by using the isothermal saturation method,10−12 the solubility data of gatifloxacin in 12 organic solvents (methanol, ethanol, n-propanol, n-butanol, isopropanol, acetone, 1,4-dioxane, toluene, butanone, acetonitrile, ethyl acetate, and DMF) were researched at T = 273.15 to 318.15 K and P = 101.3 kPa. The experimental operation is similar to our previous research.10,11 Briefly, an excess amount of gatifloxacin was placed into the jacketed vessel containing 25 mL of corresponding solvent prepared. The experimental temperature (with an accuracy of ±0.05 K) was controlled by circulating water bath. The suspension was densely mixed by a magnetic agitator operating at 350 rpm speed. Sampling and analysis was done every 2 h by using a 2 mL syringe connected with a 0.2 μm pore filter. If the solute concentration obtained by two analyses is the same, it is considered that the solid−liquid system reaches equilibrium state. Then, the stirring was stopped and permitted to settle for 2 h before sampling. After that, a 5 mL preheated syringe

(1)

where x represents the solubility of gatifloxacin in mole fraction in 12 pure organic solvents at the studied temperature T in Kelvin; A, B, and C are the model parameters. 2.2. Buchowski−Ksiazaczak λh Equation. As expressed in eq 2, the λh equation is another function of solubility data and absolute temperature T, which is proposed by Buchowski and co-workers. However, the melting point of the solute is needed in the calculation.15,16 For many solid−liquid equilibrium systems, this model can well be used to describe the experimental solubility by changing the values of adjustable parameters λ and h, and ÄÅ É ij 1 ÅÅ λ(1 − x) ÑÑÑÑ 1 yzz lnÅÅÅ1 + − ÑÑ = λhjjj z j T /K ÅÅÇ ÑÑÖ x Tm/K zz{ (2) k As described, Tm represents the melting temperature of gatifloxacin; the unit is Kelvin. λ and h are model parameters.

3. SECTION OF EXPERIMENT 3.1. Experimental Materials. Gatifloxacin (0.997 in mass fraction purity determined by a high-performance liquid phase B



Article

Table 2. Experimental and Calculated Mole Fraction Solubility of Gatifloxacin in 12 Pure Solvents within the Temperature range from T/K = (273.15 to 318.15) under 101.1 kPaa solvent methanol

n-propanol

ethanol

isopropanol

T/K

103exp

103cal(1)

103cal(2)

103exp

103cal(1)

103cal(2)

103exp

103cal(1)

103cal(2)

103exp

103cal(1)

103cal(2)

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 100RAD

0.190 0.232 0.294 0.360 0.438 0.531 0.637 0.752 0.902 1.071

0.19 0.237 0.292 0.358 0.436 0.528 0.635 0.759 0.903 1.068 0.56

0.191 0.237 0.292 0.357 0.435 0.526 0.633 0.759 0.905 1.076 0.77

0.261 0.326 0.403 0.489 0.585 0.698 0.829 0.984 1.158 1.362

0.266 0.327 0.399 0.484 0.583 0.699 0.832 0.985 1.16 1.36 0.52

0.267 0.327 0.398 0.482 0.581 0.695 0.829 0.984 1.163 1.371 0.72

0.364 0.445 0.545 0.655 0.778 0.922 1.086 1.273 1.487 1.732

0.368 0.448 0.542 0.651 0.777 0.922 1.087 1.276 1.489 1.729 0.36

0.370 0.449 0.541 0.648 0.772 0.916 1.082 1.274 1.494 1.746 0.74

0.123 0.158 0.204 0.254 0.322 0.401 0.498 0.613 0.751 0.912

0.123 0.158 0.202 0.256 0.322 0.402 0.498 0.613 0.75 0.912 0.28

0.123 0.158 0.202 0.256 0.321 0.401 0.497 0.612 0.751 0.915 0.35

solvent n-butanol T/K

3

3

10 exp

10 cal(1)

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 100RAD

1.054 1.216 1.434 1.686 1.948 2.246 2.604 2.988 3.441 3.952

1.049 1.229 1.436 1.673 1.943 2.251 2.6 2.996 3.443 3.948 0.35

acetone 3

10 cal(2)

3

3

10 exp

10 cal(1)

1.043 1.228 1.438 1.677 1.948 2.256 2.603 2.996 3.439 3.939 0.39

0.810 0.942 1.113 1.302 1.523 1.766 2.036 2.346 2.697 3.093

0.805 0.949 1.114 1.303 1.518 1.762 2.038 2.349 2.699 3.091 0.24

butanone 3

10 cal(2)

3

3

10 exp

10 cal(1)

0.805 0.950 1.115 1.303 1.517 1.760 2.036 2.347 2.699 3.096 0.26

1.576 1.863 2.186 2.567 3.002 3.488 4.048 4.678 5.390 6.197

1.576 1.861 2.19 2.567 2.998 3.489 4.047 4.678 5.392 6.196 0.06

acetonitrile 3

10 cal(2)

3

10 exp

103cal(1)

103cal(2)

1.573 1.861 2.192 2.570 3.001 3.491 4.046 4.676 5.389 6.195 0.10

1.302 1.498 1.768 2.081 2.435 2.811 3.222 3.696 4.241 4.855

1.288 1.518 1.78 2.078 2.416 2.798 3.228 3.709 4.247 4.847 0.53

1.292 1.520 1.780 2.075 2.411 2.791 3.220 3.705 4.252 4.869 0.57

solvent ethyl acetate

1,4-dioxane

T/K

103exp

103cal(1)

103cal(2)

273.15 278.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 100RAD

3.227 3.779 4.396 5.092 5.883 6.789 7.781 8.934 10.21 11.65

3.236 3.775 4.391 5.09 5.883 6.781 7.793 8.933 10.21 11.65 0.09

3.224 3.773 4.395 5.099 5.893 6.789 7.797 8.930 10.20 11.63 0.10

103exp

0.952 1.111 1.288 1.492 1.717 1.983 2.283

103cal(1)

0.954 1.109 1.287 1.49 1.721 1.984 2.282 0.14

N,N-dimethylformamide

toluene 103cal(2)

0.951 1.109 1.289 1.492 1.722 1.983 2.278 0.11

103exp

103cal(1)

103cal(2)

103exp

103cal(1)

103cal(2)

0.059 0.081 0.109 0.146 0.199 0.261 0.344 0.446 0.577 0.742

0.059 0.081 0.11 0.148 0.197 0.261 0.343 0.446 0.577 0.741 0.31

0.058 0.080 0.110 0.148 0.198 0.262 0.343 0.447 0.577 0.739 0.44

2.586 3.051 3.587 4.175 4.864 5.657 6.525 7.515 8.639 9.891

2.59 3.05 3.579 4.182 4.868 5.647 6.527 7.521 8.637 9.89 0.10

2.587 3.051 3.581 4.184 4.869 5.645 6.523 7.516 8.636 9.900 0.09

a Standard uncertainties u are u(T) = 0.05 K and u(p) = 0.45 kPa; the relative standard uncertainty ur is ur(x) = 0.022. cal(1) and cal(2) represent the values calculated via eq 1 and eq 2, respectively.

connected with a filter (PTFE 0.2 um) was used to extract supernatant, then the corresponding weighing work was carried out, and finally the dilution and gatifloxacin content were analyzed. Solubility determination of gatifloxacin in each solvent was carried out three times, and the average value was obtained to reduce the experimental deviation. The solubility of gatifloxacin (in mole fraction) (xw,T) in selected organic solvents was obtained by eq 3 x w,T =

m1/M1 m1/M1 + m2 /M 2

3.3. Analysis Method. High-performance liquid chromatography (HPLC, Agilent-1260) was applied to determine the concentration of gatifloxacin in the solid−liquid equilibrium system. An LP-C18 (250 mm × 4.6 mm) reversed-phase column was used in the detection process. The temperature was 303 K, and the wavelength of the ultraviolet detector was 284 nm. Methanol with chromatographic purity was used as the mobile phase, and the flow rate was 1.0 mL·min−1. In order to reduce the deviation caused by concentration detection, each sample needs to be analyzed three times, and the average value is taken as the final true concentration. 3.4. X-ray Powder Diffraction. The crystal of gatifloxacin was identified by X-ray powder diffraction (XPRD), which was

(3)

where m1 is the mass of gatifloxacin and m2 is the mass of organic solvent. M1 and M2 are the corresponding molar masses. C



Article

Figure 3. Mole fraction solubility x of gatifloxacin in 12 pure solvents.

298.15 K) > n-propanol (0.922 × 10−3, 298.15 K) > ethanol (0.698 × 10−3, 298.15 K) > methanol (0.531 × 10−3, 298.15 K) > isopropanol (0.401 × 10−3, 298.15 K) > toluene (0.261 × 10−3, 298.15 K). At 298.15 K, the solubility of ethyl acetate is 26 times that of toluene. Therefore, the dissolving capacity of gatifloxacin in different solvents is quite different. In five alcohols, the solubility of gatifloxacin increases with the increase of carbon chain length except for isopropanol; the possible reason is that the steric hindrance of hydroxyl groups on isopropanol hinders the interaction between hydroxyl groups and solute molecules. For other solvents, the order of solubility is the same as that of solvent polarity except for ethyl acetate, butanone, and acetonitrile. Moreover, in the range of temperature studied, the solubility of this drug in each solvent increased with the increase of temperature. Therefore, we can make gatifloxacin crystallize with high purity by lowering the temperature of the solution. In order to research the influence of solvation interaction on dissolving capacity, on the basis of the theory of multiple linear regression analysis (MLRA), a modified version of LSER (KAT-LSER) is put forward and presented in eq 4.17,18

Table 3. Hildebrand Solubility Parameters (δH) and Solvatochromic Parameters α, β, and π* for the Selected Solventsa solvent

α

β

π*

δH2/1000 (J/cm3)

acetonitrile toluene 1,4-dioxane isopropanol ethyl acetate acetone butanone methanol n-butanol DMF ethanol n-propanol

0.19 0 0 0.76 0 0.08 0.06 0.98 0.84 0.00 0.86 0.84

0.40 0.11 0.37 0.84 0.45 0.43 0.48 0.66 0.84 0.69 0.75 0.90

0.75 0.54 0.55 0.48 0.55 0.71 0.67 0.60 0.47 0.88 0.54 0.52

0.5806 0.3334 0.4194 0.5630 0.331 0.3994 0.3648 0.8797 0.5333 0.6126 0.5630 0.6025

a

Taken from refs 17 and 18.

carried out on a HaoYuan DX-2700B (HaoYuan, China) instrument. The samples were determined by Cu Kα radiation (λ = 1.54184 nm), and the tube voltage and current were set at 40 kV and 30 mA, respectively. The data were collected at room temperature from 10 to 80° (2-Theta) at a scan speed of 5 deg·min−1 under atmospheric pressure.

ln(x) = c0 + c1α + c 2 β + c3π * + c4

Vsδ H 2 100RT

(4)

Some physical variables used in the equation are as follows: the molar volume of solute (Vs), the gas constant (R), and the temperature in Kelvin (T). The main properties of solvents are the hydrogen bond acidity (α), hydrogen bond basicity (β), dipolarity/polarizability (π*), and Hildebrand solubility parameter (δH2), respectively. The physical meaning of the coefficient part of the equation is mainly as follows: c0 is a constant part of the equation, depending only on the solute. The solute−solvent interaction through hydrogen bonding was reflected by the coefficient of c1 and c2 and the solute’s sensitivity to the nonspecific electrostatic interactions of gatifloxacin solvent (c3). By consulting the literature,17,18 the properties of solvents (α, β, π*, and δH2) obtained are listed in Table 3. On the basis of the properties of solvents, the result of MLRA was obtained and described as eq 5.

4. RESULTS AND DISCUSSION 4.1. Results of X-ray Powder Diffraction. The solid phase in saturated liquid (the equilibrium solid phase was taken out, and the corresponding solvent was also removed) and raw material were analyzed by X-ray powder diffraction (PXRD). The result was shown in Figure 2. From Figure 2, we could find that the XRD characteristic peaks of raw materials are the same as those of excess solids in each saturated solution. In other words, before and after the experiment, the crystalline form of the gatifloxacin has not changed and no solvate has been formed. 4.2. Solubility Data. In Table 2 and Figure 3, the results of the measured solubility in 12 pure organic solvents with T = 273.15 to 318.15 K and P = 101.3 kPa were presented. Some information revealed through this table and figure can be found, at a given temperature, in all studied pure solvents; the largest one was found in ethyl acetate and the lowest in toluene; it decreases in the following order: ethyl acetate (6.789 × 10−3, 298.15 K) > DMF (5.657 × 10−3, 298.15 K) > butanone (3.488 × 10−3, 298.15 K) > acetonitrile (2.811 × 10−3, 298.15 K) > n-butanol (2.246 × 10−3, 298.15 K) > acetone (1.766 × 10−3, 298.15 K) > 1,4-dioxane (1.288 × 10−3,

ln(x) = −8.75 − 2.41α + 3.66β + 1.99π * − 0.347

Vsδ H 2 100RT

(5)

The positive coefficient of β and π* indicates that the solubility is positively correlated with hydrogen bond acceptance interaction and nonspecific dipolarity/polarizability interaction. However, the coefficient of α is negative, and it is D



Article

Table 4. Values of Parameters Obtained with Solubility Models λh equation

modified Apelblat equation solvent

A

B

C

104 RMSD

λ

h

104 RMSD

methanol ethanol n-propanol isopropanol n-butanol acetone butanone acetonitrile ethyl acetate toluene 1,4-dioxane DMF

−2.533 −1.600 5.471 −2.455 −50.318 −31.358 −36.231 −20.288 −42.590 −19.598 −63.260 −31.524

−3060.238 −2933.546 −3097.070 −3537.994 −233.093 −1112.319 −906.730 −1546.562 −451.772 −3673.046 289.840 −1044.865

0.922 0.732 −0.364 1.141 7.899 5.046 5.900 3.439 6.864 4.154 9.764 5.239

0.031 0.028 0.027 0.01 0.07 0.04 0.02 0.12 0.06 0.01 0.02 0.05

0.0155 0.0165 0.0178 0.0220 0.0253 0.0207 0.0440 0.0313 0.0690 0.0448 0.0156 0.0666

208556.04 183914.28 160336.00 173229.34 93544.40 116447.66 56127.97 75696.15 33033.17 108917.48 156032.13 36178.39

0.04 0.05 0.07 0.01 0.08 0.04 0.03 0.15 0.09 0.01 0.03 0.06

Figure 4. Experimental and calculated mole fraction solubility of gatifloxacin in 12 pure solvents. The symbols indicate experimental values; the solid line and dotted line represent calculated data via the λh equation and the modified Apelblat equation, respectively.

of nonliner regression.19,20The objective function is expressed as

shown that the hydrogen bond donor interaction between solvent and solute is unfavorable. The negative sign of the coefficient of

Vsδ H 2 100RT

indicates the solubility decreases as the self-

F=

cohesiveness of the solvent increases. The solvent−solvent interaction has an unfavorable influence on the solubility of the solute. Finally, we found that hydrogen bond acidity accounted for 14.04% of the total solvent effect, hydrogen bond basicity for 21.33%, dipolarity/polarizability for 11.60%, and cavity term for 2.02% of the total solvent effect. The calculated results show that the selected parameters accounted for 48.99% of the total solvent effect. 4.3. Solubility Correlation and Calculation. The experimental data of gatifloxacin in the selected solvents are correlated and computed by eq 1 and eq 2 with the method

e c − ln ww,T )2 ∑ (ln x w,T i=1

(6)

where ln xew,T represents the logarithm of solubility determined (in mole fraction) during experiment and ln xcw,T represents the logarithm of the computed ones. The deviation between the calculated values by the different models and experimental ones was evaluated by the relative average deviation (RAD) and root-mean-square deviation (RMSD). These two criteria are expressed by the following eqs 7 and 8. E


Journal of Chemical & Engineering Data RAD =

1 N

c e ji |x w,T − x w,T| zyz zz e z x w,T k {

∑ jjjj N

i=1

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(4) King, D. E.; Malone, R.; Lilley, S. H. New classification and update on the quinolone antibiotics. American Family Physician 2000, 61, 2741−2748. (5) Li, Q.; Zhao, S. M.; Luo, Z. F.; Sun, Y. G. Process improvement of synthesis of gatifloxacin. Fine Chemical Intermediates 2009, 39, 37− 40. (6) Zhou, W.; Li, R. D. Synthesis of gatifloxacin. Central South Pharmacy 2010, 8, 751−753. (7) Chava, S.; Gorantala, S. R.; Indukuri, V. S. K. An improved process for the preparation of gatifloxacin. WO Patent 2005,009,970, Feb 3, 2005. (8) Kalam, M. A.; Sultana, Y.; Ali, A.; Aqil, M.; Anil, K.; Chuttani, M. K. Preparation, characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system. J. Drug Target. 2010, 18, 191−204. (9) Niddam, H. V.; Dolitzky, B. Z.; Pilarski, G.; Sterimbaum, G. Synthesis of gatifloxacin. US Patent 7,531,656, May 12, 2009. (10) Wang, J.; Xu, A. L.; Xu, R. J. Determination and correlation of terephthaldialdehyde solubility in (ethanol, isopropanol, ethyl acetate, isopentanol) + N,N-dimethylformamide mixed solvents at temperatures from 273.15 to 318.15 K. J. Chem. Thermodyn. 2017, 105, 327− 336. (11) Xu, A. L.; Xu, R. J.; Wang, J. Solubility determination and thermodynamic modeling of terephthaldialdehyde in ten organic solvents from T = (273.15 to 318.15) K and mixing properties of solutions. J. Chem. Thermodyn. 2016, 102, 188−198. (12) Yao, G. B.; Li, Z. H.; Xia, Z. X.; Yao, Q. C. Solubility of Nphenylanthranilic acid in nine organic solvents from T = (283.15 to 318.15) K: Determination and modeling. J. Chem. Thermodyn. 2016, 103, 218−227. (13) Apelblat, A.; Manzurola, E. Solubilities of o-acetylsalicylic, 4aminosalicylic, 3,5-dinitrosalicylic, and p-toluic acid, and magnesiumDL-aspartate in water from T = (278 to 348) K. J. Chem. Thermodyn. 1999, 31, 85−91. (14) Apelblat, A.; Manzurola, E. Solubilities of L-aspartic, DLaspartic, DL-glutamic, p-hydroxybenzoic, o-anistic, p-anisic, and itaconic acids in water from T = 278K to T = 345K. J. Chem. Thermodyn. 1997, 29, 1527−1533. (15) Buchowski, H.; Ksiazczak, A.; Pietrzyk, S. Solvent activity along a saturation line and solubility of hydrogen-bonding solids. J. Phys. Chem. 1980, 84, 975−979. (16) Wang, J.; Xu, R. J.; Xu, A. L. Solubility determination and thermodynamic functions of 2-chlorophenothiazine in nine organic solvents from T = 283.15 K to T = 318.15 K and mixing properties of solutions. J. Chem. Thermodyn. 2017, 106, 132−144. (17) Kamlet, M. J.; Doherty, R. M.; Abboud, J. L. M.; Abraham, M. H.; Taft, R. W. Linear solvation energy relationships: 36. Molecular properties governing solubilities of organic nonelectrolytes in water. J. Pharm. Sci. 1986, 75, 338−349. (18) Maitra, A.; Bagchi, S. Study of solute-solvent and solventsolvent interactions in pure and mixed binary solvents. J. Mol. Liq. 2008, 137, 131−137. (19) Yao, G. B.; Yao, Q. C.; Xia, X. Z.; Li, Z. H. Solubility determination and correlation for o -phenylenediamine in (methanol, ethanol, acetonitrile and water) and their binary solvents from T = (283.15−318.15) K. J. Chem. Thermodyn. 2017, 105, 179−186. (20) Shao, D. F.; Yang, Z. H.; Zhou, G. Q. Aniracetam Solubility in Pure and Binary Solvents: Effect of Molecular Interaction and Analysis of Crystallized Products. J. Chem. Eng. Data 2018, 63, 2681− 2688.

(7)

N

RMSD =

c e ∑i = 1 (x w,T )2 − x w,T

N

(8)

N in the above two equations represents the number of experimental points. By the nonlinear least-squares method with Mathcad software, the model parameters of eq 1 and eq 2 are obtained and tabulated in Table 4, together with the values of RAD and RMSD. The calculated solubility of gatifloxacin via the regressed model parameters in those solvents are also presented in Table 4. Moreover, experimental and model calculated values are presented in Figure 4. The maximum values of the relative average deviations (RADs) and the root-mean-square deviations (RMSDs) are 0.77 × 10−2 and 0.15 × 10−4, respectively. Those two models can be employed to describe the solubility behavior of gatifloxacin in all studied solvents.

5. CONCLUSION The results of solubility determined in different pure solvents, including methanol, ethanol, n-propanol, isopropanol, n-butanol, acetonitrile, acetone, ethyl acetate, butanone, 1,4dioxane, toluene, and N,N-dimethylformamide (DMF), were obtained at T = 273.15 to 318.15 K and P = 101.3 kPa. Moreover, the solubility data of gatifloxacin in those 12 pure solvents is positively correlated with temperature. At a given temperature range, they gradually decrease in the following order: ethyl acetate > DMF > butanone > acetonitrile > n-butanol > acetone >1,4-dioxane > n-propanol > ethanol > methanol > isopropanol > toluene. The (KAT-LSER) model was applied to analyze the effect of the solute−solvent intermolecular interactions on the solubility data in those pure solvents. The modified Apelblat equation and the λh equation showed well the dependence of solubility ones upon temperature. The maximum values of RAD and RMSD are 0.77 × 10−2 and 0.15 × 10−4, respectively. In other words, these two models all can provide a good description of the experimental solubility of solute in different solvents.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Renjie Xu: 0000-0001-5541-1622 Jian Wang: 0000-0001-5882-3470 Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Caianelo, M.; Rodrigues, S. C.; Maniero, M. G.; Guimarães, J. R. Antimicrobial activity against Gram-positive and Gram-negative bacteria during gatifloxacin degradation by hydroxyl radicals. Environ. Sci. Pollut. Res. 2017, 24, 6288−6298. (2) Kostelidou, A.; Kalogiannis, S.; Begou, O. A.; Perdih, F.; Turel, I.; Psomas, G. Synthesis, structure and biological activity of copper(II) complexes with gatifloxacin. Polyhedron 2016, 119, 359−370. (3) Mignot, A.; Guillaume, M.; Brault, M.; Gualano, V.; Millérioux, L.; Göhler, K.; Stahlberg, H. J. Multiple-dose pharmacokinetics and excretion balance of gatifloxacin, a new fluoroquinolone antibiotic, following oral administration to healthy Caucasian volunteers. Chemotherapy 2002, 48, 116−121. F


Measurement and Correlation of Solubility of Gatifloxacin in 12 Pure

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