Received: 02 Apr 2019
Revised: 22 May 2019
Accepted: 15 Jun 2019
Published online: 06 Jul 2019
Solubility and Solution Thermodynamics of Tylosin in Pure Solvents and Mixed Solvents at Various Temperatures
Yanmin Shen1,2* Wenju Liu1 Zehua Bao1 and Zhanhu Guo2*
1,College of Chemistry ,Chemical and Environmental Engineering, Henan University of Technology, Zhengzhou 450001, China
2,Integrated Composites Laboratory (ICL), Department of Chemical & Biomolecular Engineering, University of Tennessee, Knoxville, TN 37966, USA
Corresponding author:
Yanmin Shen E-mail: shenym1978@126.com
Zhanhu Guo E-mail: zguo10@utk.edu
ABSTRACT:
Thermodynamic data of drug is important to industrial design and industrial application. In this paper, solubility data of tylosin in pure solvents and acetone +water mixture solvents were experimentally determined from 279.75 K to 323.15 K. The experiment results indicated that solubility of tylosin in pure solvents gradually decreased and followed this order: chloroform>butylacetate >acetonitrile>tetrahydrofuran>acetone>benzene>n-butanol>ethyl acetate >n-propanol>ethanol>methanol>water, and solubility gradually decreased with water increasing in water+acetone mixture solvents. Moreover，experimental solubility increased with temperature increasing except for water（xc≥0.9281）+acetone mixture solvents. Thermodynamic models correlating solubility data showed that modified Apelblat model was litter better agreement than Van¢t Hoff model, Wilson model NRTL model in pure solvents and C/R-K model, Jouyban Acree model in acetone+water solvents by ARD,AMSD and R2. Furthermore, thermodynamic properties for dissolution process of tylosin were calculated and discussed by modified Apelblat model paramaters.[1]
Table of Content
Solubility data of tylosin in pure solvents and water+acetone mixture solvents was determined and correlated well by different thermodynamic models at various temperatures.
Keywords: Tylosin；Solubility; Thermodynamics models; Dissolution process
Introduction
Tylosin (CAS:1401-69-0, Fig. 1) is a kind of antibiotic drugs that are greatly applied livestock not only to treat disease, but also to improve the feed utilization as feed additive.1-3 Because tylosin is a medium spectrum antibiotic to treat infections caused by most Gram-positive bacteria, mycoplasmas, some Gram-negative bacteria,Chlamydia, and to increase the rates of weight gain and improve the feed efficiency of companion animals,such as cattle, chicken, turkey, and swine1-3.Therfore,investigations and research thermodynamic properties of drugs are vital to understand nature of molecular interactions and explore new fields. The solid–liquid equilibrium solubility data of drugs plays an important role separation and purification for process choosing in industry application. In this research, the solubility of tylosin were experimentally determined in chloroform, butyl acetate,acetonitrile,tetrahydrofuran,acetone,benzene,n-butanol,ethyl acetate,
n-propanol,ethanol,methanol,water and acetone+water mixture solvents, and were correlated with modified Apelblat model, Van¢t Hoff model, Wilson model, NRTL model, C/R-K model and Jouyban–Acree model from 279.75 K to 323.15 K. Furthermore, ΔsolHo, ΔsolSo and ΔsolGo for the dissolution processes of tylosin were calculated by modified Apelblat model parameters.
Fig. 1 Molecular structure of tylosin.
Experimental
Materials
In the paper, tylosin was supplied from Ningxia Tairui Pharmaceutical Co.Ltd., China and purified before use by dilution crystallization method. Purity of tylosin was determined by HPLC (type Agilent 1200, Agilent Technologies).All solvents are analytical grade without further detection. Resources information were presented in Table 1.
Table 1 Description of materials used in this paper.
|
Chemical name |
Formula |
Source |
Mass fraction purity |
|
||
|
Tylosin |
C46H77NO17 |
Ningxia Tairui Pharmaceutical |
³0.99 |
|
|
|
|
Methanol(AR) |
CH3OH |
Tianjin Wind Ship Chemical |
³0.995 |
|
|
|
|
Ethanol(AR) |
C2H5OH |
Tianjin Wind Ship Chemical |
³0.997 |
|
|
|
|
n-Propanol (AR) |
C3H7OH |
Tianjin Wind Ship Chemical |
³0.998 |
|
|
|
|
n-Butanol(AR) |
C4H9OH |
Tianjin Wind Ship Chemical |
³0.995 |
|
|
|
|
Acetone (AR) |
C4H6O |
Tianjin Wind Ship Chemical |
³0.99 |
|
|
|
|
Chloroform(AR) |
CHCl3 |
Tianjin Wind Ship Chemical |
³0.99 |
|
|
|
|
Acetonitrile(AR) |
C2H3N |
Tianjin Kermel Chemical |
³0.995 |
|
|
|
|
Butyl acetate(AR) |
C6H12O2 |
Tianjin Kermel Chemical |
³0.99 |
|
|
|
|
Ethyl acetate(AR) |
C4H8O2 |
Tianjin Kermel Chemical |
³0.995 |
|
|
|
|
Benzene(AR) |
C6H6 |
Tianjin Wind Ship Chemical |
³0.995 |
|
|
|
|
Tetrahydrofuran(AR) |
C4H8O |
Tianjin Wind Ship Chemical |
³0.995 |
|
|
|
a AR means analytical reagent. HPLC High-performance liquid chromatography.Gas chromatography.
Thermal analysis
The DSC measurements were operated for tylosin in a nitrogen atmosphere with a differential scanning calorimeter (NETZSCH, STA409PC). Tylosin sample was scanned from 270.6K to 772.9K at heating rate of 5K·min-1.
Characterization
The powder X-ray diffraction equipment (Bruker D8 Advance) was used to collect samples data and to ensure crystal form of samples. Diffraction angle was range from 2o to 50o (2q) and a scanning speed of 5 o min-1 with a current of 40 mA and a voltage of 40 kV.
Solubility determination
In this work, the gravimetric method was adopted to determine solubility of tylosin from 279.75 K to 323.15 K at the pressure of 0.1 MPa.4-5 Firstly, the excess drug of tylosin sample and a certain amount of selected solvents was set into the cylindrical double-jacketed glass container with a designed temperature(±0.05K). The glass container was kept a designed temperature with water circulating. The prepared mixed solution was stirred more than 12 h to reach dissolution equilibrium.4-5 Then, solid–liquid solution was set to stop stirring, precipitate and stratify 12 h. Next, 5 mL sampling was extracted from upper liquid and placed in double dish, weighed and set into a vacuum oven to dry for 12 h at 323.15 K. Lastly, Experimental solubility were measured at least three times to reduce mistakes. The solubility x of tylosin could be calculated by following equation:
where m1 and m2 (or mB and mC) stand for the mass of tylosin and the mass of solvents, respectively. M1 and M2 (or MB and MC) are the molar masses of tylosin and solvent, respectively. xc is initial composition of water in acetone+water mixture solvent under condition of without tylosin.
Results and discussion
DSC and XRD analysis
From DSC curve, It was shown that there was a bigger and wider peak at 547.41 K, this revealed that the drug of tylosin had not fixed melting point and decomposed before melting temperature, Because tylosin had larger molecular weight and complex structure from Fig. 1. So, the thermal decomposition temperature was 547.41K and enthalpy of fusion DHfus was 88.9 kJ·mol-1 from Fig. 2.
Fig. 2 DSC curve.
Fig. 3 presented the XRD pattern of the crystal. It could be seen that the morphologies of tylosin was not changed after recrystallization according with comparing with the powder diffraction spectrum of before and after recrystallization of tylosin.
Fig. 3 XRD pattern of before and after recrystallization of tylosin.
Solubility data
The determination solubility data of tylosin were shown in Tables 2-3 and correlated Figs. 4-6 in pure solvents and acetone+water binary solvents systems with the temperature range from 279.75-323.15K. From Table 2 and Fig. 4, the solubility values of tylosin increased with increasing temperature except for water in pure solvents, the solubility gradually decreased and followed this order: chloroform > butyl acetate > acetonitrile > tetrahydrofuran > acetone > benzene > n-butanol > Ethyl acetate > n-propanol > ethanol > methanol > water. According to the thermodynamics of solutions, solubility of tylosin in solvent are affected many factors that are solvent polarity, the same molecules self-association and the different molecules cross-association.6-7 The polarity of tylosin was weaker by Fig. 1. According with the principle of ‘‘like dissolves like,” tylosin dissolved highly in poorer polarity solvents like chloroform, butyl acetate and acetone than in stronger polarity solvents like water, methanol and ethanol. Especially, solubility of tylosin was confirmed to decrease with increasing temperature and was consistent with reference in water.8
From Table 3 and Fig. 5, in acetone+water mixture solvents, solubility values of tylosin increased with the increasing temperature when xc was less than 0.9281, and decreased with the increasing mole fraction of water in mixture solvents. Because solubility was affected obviously and sensitive with water content. All factors influencing separation ways of tylosin could be considered as temperature, toxicity, cost, source of solvent and operability of purification process. Dilution crystallization process will be selected to separate and purify for tylosin with acetone+water solvents system in industry according with solubility data measured.
Table 2 The measured and calculated mole fraction solubility of tylosin in different solvents from 279.75 to 323.15 K.
|
T/K |
102xexp |
102xcal |
T/K |
102xexp |
102xcal |
||||||
|
Apel |
Van¢t |
Wilson |
NRNL |
Apel |
Van¢t |
Wilson |
NRNL |
||||
|
Methanol |
Ethanol |
||||||||||
|
280.25 |
0.4486 |
0.4536 |
0.4195 |
0.3101 |
0.4637 |
281.75 |
0.6949 |
0.7228 |
0.6687 |
0.5073 |
0.6444 |
|
287.05 |
0.6448 |
0.5987 |
0.576 |
0.5146 |
0.6901 |
287.95 |
0.8668 |
0.9405 |
0.8991 |
0.8768 |
0.8936 |
|
292.85 |
0.7529 |
0.7576 |
0.7462 |
0.8656 |
0.718 |
293.45 |
1.1856 |
1.185 |
1.1569 |
1.2076 |
1.1321 |
|
297.85 |
0.9183 |
0.9271 |
0.9252 |
1.1682 |
0.8844 |
298.05 |
1.3738 |
1.4348 |
1.4183 |
1.6681 |
1.4277 |
|
302.55 |
1.0885 |
1.1199 |
1.1251 |
1.4968 |
1.0527 |
303.05 |
1.7245 |
1.7631 |
1.7574 |
2.0835 |
1.7667 |
|
307.15 |
1.3308 |
1.3462 |
1.3546 |
1.6775 |
1.3409 |
307.85 |
2.1497 |
2.1448 |
2.145 |
2.4057 |
2.1363 |
|
312.35 |
1.6099 |
1.6557 |
1.66 |
1.9058 |
1.632 |
312.55 |
2.581 |
2.5938 |
2.5918 |
2.7484 |
2.589 |
|
317.35 |
2.0405 |
2.018 |
2.0057 |
1.7289 |
2.085 |
317.45 |
3.1633 |
3.1566 |
3.1381 |
2.9079 |
3.102 |
|
321.65 |
2.3784 |
2.3902 |
2.3491 |
1.7092 |
2.3397 |
322.55 |
3.764 |
3.8649 |
3.8059 |
3.1401 |
3.7946 |
|
n-Propanol |
n-Butanol |
||||||||||
|
279.75 |
2.0177 |
2.0553 |
1.9293 |
1.7018 |
2.0176 |
279.75 |
1.3455 |
1.285 |
1.3618 |
1.1597 |
1.2947 |
|
287.65 |
2.328 |
2.3672 |
2.3075 |
2.3258 |
2.3139 |
287.75 |
1.7681 |
1.7683 |
1.8329 |
1.8858 |
1.8113 |
|
293.05 |
2.5884 |
2.6178 |
2.5934 |
2.7118 |
2.5418 |
293.05 |
2.1935 |
2.1544 |
2.2118 |
2.3448 |
2.2088 |
|
297.35 |
2.7577 |
2.8421 |
2.8375 |
3.2361 |
2.8526 |
297.35 |
2.5941 |
2.5095 |
2.5634 |
2.7083 |
2.5694 |
|
302.55 |
3.1517 |
3.1464 |
3.1529 |
3.2107 |
3.0045 |
302.65 |
3.1376 |
3.0016 |
3.0569 |
3.1612 |
3.067 |
|
307.45 |
3.366 |
3.4701 |
3.4708 |
3.8773 |
3.4998 |
307.15 |
3.5062 |
3.4688 |
3.5329 |
3.8061 |
3.5953 |
|
312.65 |
3.8096 |
3.8579 |
3.8306 |
3.8055 |
3.7753 |
312.05 |
4.1351 |
4.0311 |
4.1163 |
4.1614 |
4.1488 |
|
317.15 |
4.154 |
4.2348 |
4.1611 |
3.9793 |
4.1805 |
316.35 |
4.7012 |
4.5718 |
4.6887 |
4.5181 |
4.6882 |
|
321.65 |
4.5785 |
4.6545 |
4.5096 |
3.938 |
4.5512 |
321.15 |
5.3616 |
5.2288 |
5.4 |
4.9444 |
5.3461 |
|
Chloroform |
Acetonitrile |
||||||||||
|
280.25 |
3.2637 |
3.3176 |
3.2157 |
2.8894 |
3.3192 |
281.85 |
5.7934 |
5.8306 |
5.6223 |
5.2853 |
5.6922 |
|
287.05 |
4.1595 |
4.0205 |
4.029 |
3.8975 |
3.9472 |
289.35 |
6.1877 |
6.2474 |
6.1703 |
6.5079 |
6.2455 |
|
292.85 |
4.8502 |
4.7406 |
4.843 |
5.1344 |
4.8227 |
292.85 |
6.4903 |
6.4659 |
6.4335 |
6.3232 |
6.3867 |
|
297.85 |
5.4514 |
5.4667 |
5.6431 |
6.4615 |
5.8135 |
298.65 |
6.8681 |
6.8637 |
6.8799 |
7.0578 |
6.8583 |
|
302.55 |
6.4828 |
6.2523 |
6.4853 |
6.9455 |
6.3689 |
303.45 |
7.182 |
7.2289 |
7.2585 |
7.8071 |
7.3157 |
|
307.15 |
7.453 |
7.1318 |
7.4006 |
7.6318 |
7.1949 |
307.95 |
7.618 |
7.6028 |
7.6207 |
7.6391 |
7.5888 |
|
312.35 |
8.4904 |
8.2772 |
8.5517 |
8.7068 |
8.5211 |
313.25 |
7.9915 |
8.085 |
8.0562 |
8.5663 |
8.1968 |
|
317.35 |
9.6805 |
9.5525 |
9.7832 |
9.5157 |
9.9105 |
318.25 |
8.4851 |
8.5845 |
8.4754 |
8.6603 |
8.6239 |
|
321.65 |
11.064 |
10.805 |
10.947 |
9.6175 |
10.949 |
322.65 |
9.0895 |
9.0624 |
8.8508 |
7.9343 |
8.7809 |
|
Butyl acetate |
Ethyl acetate |
||||||||||
|
281.95 |
6.5687 |
6.4234 |
6.4199 |
6.0072 |
6.4454 |
282.05 |
3.7167 |
3.7369 |
3.6229 |
2.8413 |
3.7545 |
|
289.35 |
6.9708 |
6.7715 |
6.9524 |
6.8768 |
6.9065 |
289.45 |
3.8761 |
3.8556 |
3.8441 |
3.428 |
3.8369 |
|
292.75 |
7.1825 |
6.957 |
7.2019 |
7.17 |
7.1248 |
292.65 |
3.9461 |
3.9205 |
3.9402 |
3.7296 |
3.8987 |
|
298.75 |
7.5316 |
7.3259 |
7.6493 |
8.072 |
7.6306 |
298.85 |
4.0908 |
4.0698 |
4.1271 |
4.332 |
4.0557 |
|
Table 2 continued |
|||||||||||
|
T/K |
102xexp |
102xcal |
T/K |
102xexp |
102xcal |
||||||
|
Apel |
Van¢t |
Wilson |
NRNL |
Apel |
Van¢t |
Wilson |
NRNL |
||||
|
303.45 |
7.8937 |
7.6535 |
8.0058 |
8.2336 |
7.9503 |
303.35 |
4.1638 |
4.198 |
4.2633 |
5.2817 |
4.2384 |
|
307.95 |
8.1842 |
8.001 |
8.3517 |
8.9865 |
8.4158 |
307.95 |
4.3304 |
4.3469 |
4.4027 |
5.1867 |
4.3714 |
|
313.15 |
8.6832 |
8.4461 |
8.7569 |
8.8047 |
8.7427 |
313.15 |
4.5469 |
4.5378 |
4.5607 |
4.9144 |
4.5368 |
|
318.15 |
9.0999 |
8.9212 |
9.1516 |
9.3123 |
9.2487 |
317.95 |
4.7386 |
4.7363 |
4.7068 |
4.9013 |
4.7376 |
|
322.55 |
9.7004 |
9.3802 |
9.5029 |
8.4664 |
9.3327 |
322.45 |
4.9519 |
4.943 |
4.8438 |
4.6916 |
4.9297 |
|
Benzene |
Tetrahydrofuran |
||||||||||
|
281.75 |
1.7597 |
1.7321 |
1.8745 |
1.5464 |
1.6363 |
281.85 |
4.3457 |
4.2923 |
4.4041 |
4.199 |
4.1908 |
|
288.45 |
2.2856 |
2.364 |
2.4408 |
2.396 |
2.3394 |
288.45 |
4.9004 |
5.0832 |
5.0478 |
5.258 |
4.818 |
|
293.25 |
2.8574 |
2.9042 |
2.9273 |
3.0145 |
2.9194 |
293.25 |
5.482 |
5.6828 |
5.5529 |
5.5999 |
5.567 |
|
298.05 |
3.403 |
3.5207 |
3.4902 |
3.8098 |
3.6129 |
298.05 |
5.9855 |
6.296 |
6.0898 |
6.3274 |
6.1291 |
|
303.45 |
4.3595 |
4.3072 |
4.2257 |
4.4143 |
4.3729 |
303.45 |
6.9123 |
6.9939 |
6.7326 |
6.1407 |
7.0223 |
|
308.15 |
5.2081 |
5.0712 |
4.9637 |
5.0256 |
5.1011 |
308.05 |
7.4199 |
7.5881 |
7.313 |
6.9977 |
7.4941 |
|
313.05 |
6.0844 |
5.9444 |
5.8405 |
5.7978 |
5.9377 |
312.75 |
8.1896 |
8.1885 |
7.9379 |
7.2401 |
8.0053 |
|
318.15 |
7.0391 |
6.9319 |
6.8814 |
6.6836 |
6.8553 |
317.75 |
8.6256 |
8.8129 |
8.6383 |
8.8668 |
8.5522 |
|
323.15 |
7.7743 |
7.9717 |
8.0411 |
8.0956 |
7.9944 |
323.15 |
9.1533 |
9.463 |
9.4365 |
10.78 |
9.2041 |
a x exp and xcal are experimental and calculated mole fraction of tylosin in solvents;
Standard uncertainties of temperature is u(T)=0.05K, standard uncertainty of pressure is u(P)=0.3kPa; relative standard uncertainty of solubility measurement is ur(x)=2%.
Table 3 The measured and calculated mole fraction solubility of tylosin acetone(1- xc)+water (xc) solvents.
|
T/K |
100 xexp |
100 |
T/K |
100 xexp |
100 |
T/K |
100 xexp |
100 |
||||||||
|
xc=0.0000 |
xc=0.1955 |
xc=0.3629 |
||||||||||||||
|
281.75 |
2.866 |
2.8253 |
281.85 |
2.696 |
2.7794 |
281.85 |
2.521 |
2.6199 |
||||||||
|
287.95 |
3.256 |
3.337 |
288.65 |
3.187 |
3.2617 |
288.65 |
2.979 |
3.0768 |
||||||||
|
293.45 |
4.014 |
3.8525 |
293.35 |
3.826 |
3.6354 |
293.35 |
3.423 |
3.4064 |
||||||||
|
298.05 |
4.273 |
4.3322 |
298.15 |
4.175 |
4.0541 |
298.15 |
3.857 |
3.7516 |
||||||||
|
302.85 |
4.771 |
4.884 |
302.95 |
4.51 |
4.5134 |
302.95 |
4.173 |
4.1027 |
||||||||
|
307.75 |
5.297 |
5.5054 |
307.95 |
4.873 |
5.0382 |
307.85 |
4.535 |
4.4644 |
||||||||
|
312.65 |
5.997 |
6.1901 |
312.65 |
5.544 |
5.5783 |
312.55 |
4.839 |
4.8115 |
||||||||
|
316.75 |
6.883 |
6.8152 |
317.65 |
6.186 |
6.2063 |
317.55 |
5.117 |
5.1780 |
||||||||
|
323.25 |
7.898 |
7.9114 |
322.05 |
6.873 |
6.8080 |
321.85 |
5.421 |
5.4885 |
||||||||
|
xc=0.4466 |
xc=0.5182 |
xc=0.6827 |
||||||||||||||
|
279.95 |
2.287 |
2.2910 |
281.85 |
1.977 |
1.9773 |
281.45 |
0.906 |
0.8989 |
||||||||
|
287.85 |
2.654 |
2.6740 |
288.65 |
2.296 |
2.2747 |
288.05 |
0.995 |
1.0291 |
||||||||
|
293.25 |
3.001 |
2.9477 |
293.35 |
2.482 |
2.4910 |
293.75 |
1.149 |
1.1460 |
||||||||
|
Table 3 continued |
||||||||||||||||
|
T/K |
100 xexp |
100 |
T/K |
100 xexp |
100 |
T/K |
100 xexp |
100 |
||||||||
|
297.95 |
3.169 |
3.1925 |
298.15 |
2.703 |
2.7201 |
298.55 |
1.26 |
1.2470 |
||||||||
|
302.85 |
3.452 |
3.4529 |
302.85 |
2.931 |
2.9518 |
302.95 |
1.359 |
1.3411 |
||||||||
|
307.65 |
3.686 |
3.7122 |
307.75 |
3.207 |
3.2003 |
307.85 |
1.478 |
1.4471 |
||||||||
|
312.65 |
3.975 |
3.9854 |
312.45 |
3.487 |
3.4444 |
313.15 |
1.581 |
1.5624 |
||||||||
|
316.75 |
4.247 |
4.2109 |
317.45 |
3.706 |
3.7094 |
318.05 |
1.637 |
1.6690 |
||||||||
|
322.85 |
4.534 |
4.5473 |
321.65 |
3.922 |
3.9355 |
322.95 |
1.779 |
1.7750 |
||||||||
|
xc=0.7634 |
xc=0.8288 |
xc=0.8827 |
||||||||||||||
|
281.45 |
0.627 |
0.6391 |
281.55 |
0.488 |
0.4930 |
281.15 |
0.201 |
0.1980 |
||||||||
|
288.05 |
0.736 |
0.7409 |
288.05 |
0.584 |
0.5755 |
288.05 |
0.235 |
0.2365 |
||||||||
|
293.75 |
0.846 |
0.8318 |
293.75 |
0.646 |
0.6531 |
293.75 |
0.266 |
0.2712 |
||||||||
|
298.55 |
0.935 |
0.9095 |
298.55 |
0.72 |
0.7222 |
297.35 |
0.289 |
0.2943 |
||||||||
|
302.95 |
0.981 |
0.9810 |
302.95 |
0.786 |
0.7882 |
302.95 |
0.337 |
0.3322 |
||||||||
|
307.85 |
1.05 |
1.0604 |
307.65 |
0.858 |
0.8614 |
307.45 |
0.371 |
0.3641 |
||||||||
|
312.95 |
1.166 |
1.1420 |
312.85 |
0.966 |
0.9453 |
312.75 |
0.413 |
0.4032 |
||||||||
|
317.95 |
1.222 |
1.2202 |
317.75 |
1.043 |
1.0268 |
317.55 |
0.437 |
0.4400 |
||||||||
|
322.85 |
1.291 |
1.2945 |
322.55 |
1.089 |
1.1086 |
322.35 |
0.473 |
0.4779 |
||||||||
|
xc=0.9281 |
xc=0.9667 |
xc=1 |
||||||||||||||
|
281.95 |
0.12 |
0.1195 |
281.95 |
0.0492 |
0.0502 |
281.95 |
0.0192 |
0.0194 |
||||||||
|
288.45 |
0.0992 |
0.1010 |
288.45 |
0.0431 |
0.0421 |
288.45 |
0.0147 |
0.0147 |
||||||||
|
293.25 |
0.0922 |
0.0906 |
293.25 |
0.0381 |
0.0372 |
293.25 |
0.0123 |
0.0121 |
||||||||
|
298.05 |
0.0842 |
0.0824 |
298.05 |
0.034 |
0.0330 |
298.05 |
0.0102 |
0.0101 |
||||||||
|
303.25 |
0.0744 |
0.0754 |
303.15 |
0.0299 |
0.0292 |
303.15 |
0.0087 |
0.0084 |
||||||||
|
307.95 |
0.068 |
0.0703 |
307.85 |
0.0257 |
0.0261 |
307.75 |
0.0074 |
0.0071 |
||||||||
|
312.65 |
0.067 |
0.0663 |
312.55 |
0.0238 |
0.0235 |
312.45 |
0.0057 |
0.0061 |
||||||||
|
317.75 |
0.0635 |
0.0628 |
317.75 |
0.0202 |
0.0210 |
317.75 |
0.0049 |
0.0052 |
||||||||
|
322.65 |
0.0602 |
0.0603 |
322.35 |
0.0186 |
0.0190 |
322.15 |
0.0043 |
0.0045 |
||||||||
a x exp and xcal are experimental and calculated mole fraction of tylosin in solvents;
xc is initial composition of water in acetone+water mixture solvent under condition of without tylosin;
Standard uncertainties of temperature is u(T) = 0.05 K, standard uncertainty of pressure is u(P) = 0.3 kPa; relative standard uncertainty of solubility measurement is ur(x) = 2%.
Solubility modeling
Modified Apelblat model
The modified Apelblat model is widely applied and well-correlated the relation between solubility data and different temperatures, which is described as following equation9,10:
(4)
where x is experimental determination mole fraction solubility, T is thermodynamic absolute temperature. A, B and C are three model parameters in Eq. (4) and are listed in the Table 4 and Table 6. ARD is named corresponding average absolute deviation, and RMSD is named root mean square deviations, ARD and RMSD are calculated with Eq. (5) and Eq. (6) :
(5)
The root-mean-square deviations (RM) is defined as follows:
(6)
where xi,cal and xi represent the calculated and determination values, n is total times of experimental points. ARD and RMSD are presented in Tables 4-8.
Van¢t Hoff model
Based on thermodynamic principles of the solid-liquid equilibrium13,14,the Van¢t Hoff model is considered as the simplest equation describing relationship of solubility and temperature.
(7)
In Eq. (7), the two model parameters of a and b are gained from fitting results by solubility data and are shown in Table 4.
where V1 and V2 represent mole volumes of solute and pure solvent, m3·mol-1, the two parameters of and stand for energy of cross interaction between different molecule, J·mol-1 and are shown in Table 5.
NRTL model
Another about activity coefficient equal is expressed as NRTL model, where three parameters exist in binary interaction, NRTL model can be organized and simplified into the following equations.16,17,18
where △g12 and △g21 are considered as model constants and stand for energy of cross interaction between different molecules, J×mol-1; a is a parameter related to non-randomness of a solution; all of parameters are presented in Table 5.
C/R-K model
At a constant temperature, C/R-K model is applied as the most appropriate and direct model to build the inherently complex relationship between composition and solubility in binary mixture solvents. The model can be simplify and deduced to Eq.(16) in ref19:
where there are five model parameters from B0 to B4 in Eq.(16); xc represents initial composition of water in mixture solvent; B0,B1,B2,B3 and B4 are presented in Table 7.
Jouyban Acree model
Jouyban Acree model19 is frequently applied another semi-empirical equation to correlate solubility data and temperature in mixtures solvent, which is described to Eq.(17) as follows:
ln(XA)B and ln(XA)c can be expressed with modified Apelblat model as Eq. (18) and Eq. (19) Eq.(17) can be simplified to Eq. (20) by the combination of Eq. (17), Eq. (18) and Eq. (19) . 20-23
where x represents solubility data of tylosin in acetone+water solvents, xc represents initial composition of water in mixture solvent; there are nine model parameters from A1 to A9 , All of parameters are presented in Table 8, together with R2.
The solubility values of tylosin in pure solvents were fitted by modified Apelblat model, Van¢t Hoff model, Wilson model and NRTL model, respectively. The computed solubility values with the modified Apelblat model are plotted in Fig. 4. Comparing of the total ARD, RMSD and R2 from Tables 4-5. Tables 4-5 showed that R2 values varied more than 0.993, ARD and RMSD values were less than 2.69% and 2.2×10-3 by modified Apelblat model. It could be said that the modified Apelblat model was little better than other three models. At the same time, the solubility values of tylosin in acetone+water solvents were fitted by modified Apelblat model,C/R-K model and Apelblat-Jouyban Acree model, respectively. The computed solubility values are plotted with the modified Apelblat model in Fig. 5 and with the C/R-K model in Fig. 6. Comparing of the total ARD, RMSD and R2 from Tables 6-8. It indicated that R2 values varied between 0.991 and 0.999 from modified Apelblat model, ARD and RMSD values from modified Apelblat model were less than 3.11% and 1.12×10-3 and less than from C/R-K model and Apelblat-Jouyban Acree model. These data in Tables 4-8 indicated that modified Apelblat model can litter better agree with solubility data of tylosin and provides reliable results for data prediction in pure solvents and in acetone+water solvents at varying temperature between 279.75 K and 323.15 K under the pressure of 0.1 MPa.
Table 4 Parameters of the modified Apelblat model and Van¢t Hoff model for tylosin in pure solvent.
|
Solvents |
Modified Apelblat model |
Van¢t Hoff model |
|||||||||
|
A |
B |
C |
R2 |
102ARD |
103RMSD |
a |
b |
R2 |
102ARD |
103RMSD |
|
|
Methanol |
-129.96 |
2531.45 |
20.5 |
0.998 |
2.03 |
0.26 |
7.91 |
-3750.8 |
0.996 |
3.33 |
0.36 |
|
Ethanol |
-109.64 |
1561.19 |
17.58 |
0.998 |
2.54 |
0.49 |
8.74 |
-3873.4 |
0.999 |
1.95 |
0.3 |
|
n-Propanol |
-129.57 |
4143.14 |
19.68 |
0.998 |
1.76 |
0.63 |
2.57 |
-1823.4 |
0.994 |
1.52 |
0.58 |
|
n-Butanol |
77.6 |
-6220.28 |
-10.6 |
0.999 |
252 |
0.92 |
6.39 |
-2989.5 |
0.999 |
1.29 |
0.4 |
|
Chloroform |
-116.15 |
2883.04 |
18.18 |
0.998 |
2.39 |
1.88 |
6.08 |
-2667.2 |
0.998 |
1.31 |
0.98 |
|
Acetonitrile |
-98.2 |
3455.62 |
14.73 |
0.997 |
0.61 |
0.55 |
0.71 |
-1011.4 |
0.99 |
0.99 |
1.05 |
|
Butyl acetate |
-113.48 |
4259.55 |
16.96 |
0.998 |
2.69 |
2.2 |
0.37 |
-878.49 |
0.984 |
1.25 |
1.17 |
|
Ethyl acetate |
-123.32 |
4860.94 |
18.22 |
0.997 |
0.43 |
0.19 |
-1 |
-653.76 |
0.968 |
1.28 |
0.66 |
|
Benzene |
177.45 |
-10976.2 |
-25.27 |
0.996 |
2.25 |
1.12 |
7.39 |
-3202.6 |
0.991 |
3.97 |
1.77 |
|
Tetrahydrofuran |
141.76 |
-7976.67 |
-20.68 |
0.993 |
2.53 |
1.94 |
2.84 |
-1680.6 |
0.989 |
1.97 |
1.59 |
a A, B and C are parameters of Apelblat model; a and b are parameters of Van¢t Hoff model;
Table 5 Parameters of Wilson model and NRTL model for tylosin in pure solvent.
|
Solvents |
Wilson model |
NRTL model |
|||||||||
|
△λ12 |
△λ21 |
R2 |
102ARD |
103RMSD |
△g12 |
△g21 |
a |
R2 |
102ARD |
103RMSD |
|
|
Methanol |
-6156.2 |
332.82 |
0.931 |
24.28 |
3.38 |
-11760 |
30168 |
0.3 |
0.998 |
3.1 |
0.33 |
|
Ethanol |
-17079 |
508.36 |
0.969 |
12.81 |
2.98 |
-2273 |
-20953 |
1.63 |
0.999 |
2.77 |
0.42 |
|
n-Propanol |
-13416 |
-1162.47 |
0.992 |
8.13 |
3.41 |
-4356 |
-15589 |
0.89 |
0.996 |
1.84 |
0.77 |
|
n-Butanol |
-20944 |
-373.76 |
0.995 |
5.93 |
2.06 |
63319 |
-58013 |
0.04 |
0.999 |
2.71 |
0.46 |
|
Chloroform |
-28851 |
504.12 |
0.993 |
7.66 |
6.43 |
-3154 |
-25430 |
1.05 |
0.997 |
2.55 |
1.91 |
|
Acetonitrile |
-19996 |
-1821.32 |
0.997 |
5.58 |
5.28 |
128530 |
-118240 |
0.01 |
0.989 |
1.58 |
1.49 |
|
Butyl acetate |
-17893 |
-4824.58 |
0.997 |
5.31 |
5.73 |
144729 |
-134897 |
0.01 |
0.985 |
1.61 |
1.67 |
|
Ethyl acetate |
1.3*1012 |
-4882.22 |
0.988 |
12.21 |
6.04 |
183825 |
-158117 |
0.01 |
0.995 |
0.83 |
0.4 |
|
Benzene |
-26376 |
422.85 |
0.995 |
5.89 |
2.57 |
110424 |
-37889 |
0.07 |
0.998 |
3.1 |
1.42 |
|
Tetrahydrofuran |
-24809 |
-684.71 |
0.995 |
7.5 |
7.2 |
-32038 |
413596 |
0.03 |
0.997 |
1.71 |
1.15 |
△λ12 and△λ21 are parameters of Wilson model; △g12, △g21 and a are parameters of NRTL model.
Table 6 Parameters of the Apelblat model for tylosin in acetone(1- xc)+water (xc) solvents.
|
Solvents |
A |
B |
C |
R2 |
102ARD |
103RMSD |
|
xc=0 |
-28.24 |
-791.25 |
4.87 |
0.9931 |
2.05 |
1.12 |
|
xc=0.1955 |
-42.25 |
34.37 |
6.83 |
0.9914 |
2.07 |
1.03 |
|
xc=0.3629 |
107.22 |
-6383.22 |
-15.64 |
0.9915 |
1.85 |
0.74 |
|
xc=0.4466 |
55.21 |
-3854.6 |
-8.02 |
0.9982 |
0.62 |
0.25 |
|
xc=0.5182 |
48.12 |
-3652.47 |
-6.93 |
0.9987 |
0.50 |
0.19 |
|
xc=0.6827 |
70.05 |
-4608.74 |
-10.35 |
0.9924 |
1.36 |
0.21 |
|
xc=0.7634 |
109.34 |
-6437.15 |
-16.23 |
0.9941 |
1.16 |
0.30 |
|
xc=0.8288 |
56.65 |
-4289.54 |
-8.28 |
0.9951 |
1.11 |
0.11 |
|
xc=0.8827 |
62.29 |
-4701.23 |
-9.19 |
0.9947 |
1.48 |
0.05 |
|
xc=0.9281 |
-250.46 |
12231.75 |
35.51 |
0.9931 |
1.46 |
0.01 |
|
xc=0.9667 |
-16.94 |
2254.3 |
0.24 |
0.9922 |
2.33 |
0.00 |
|
xc=1 |
-95.81 |
6680.6 |
11.27 |
0.9965 |
3.11 |
0.00 |
aA, B and C are parameters of Apelblat model;
xc is initial composition of water in acetone+water mixture solvent.
Table 7 Parameters of the C/ R-K model for tylosin in acetone(1- xc)+water (xc) solvents.
|
T/K |
B0 |
B1 |
B2 |
B3 |
B4 |
R2 |
102ARD |
103RMSD |
|
281.15 |
-3.5924 |
-0.5511 |
4.7253 |
-11.3427 |
3.4646 |
0.996 |
15.39 |
0.54 |
|
288.15 |
-3.4048 |
-0.6102 |
4.4083 |
-10.5526 |
2.9689 |
0.996 |
25.19 |
0.68 |
|
293.15 |
-3.2744 |
-0.6178 |
3.9287 |
-9.5583 |
2.4072 |
0.995 |
33.96 |
0.8 |
|
298.15 |
-3.1468 |
-0.5982 |
3.2466 |
-8.2068 |
1.6612 |
0.995 |
44.15 |
0.94 |
|
303.15 |
-3.022 |
-0.5454 |
2.3251 |
-6.4188 |
0.6782 |
0.995 |
55.58 |
1.08 |
|
308.15 |
-2.8999 |
-0.4615 |
1.181 |
-4.2244 |
-0.5275 |
0.995 |
68.33 |
1.22 |
|
313.15 |
-2.7803 |
-0.3376 |
-0.2537 |
-1.4757 |
-2.0516 |
0.994 |
81.79 |
1.36 |
|
318.15 |
-2.6633 |
-0.1848 |
-1.89 |
1.6387 |
-3.7771 |
0.995 |
95.57 |
1.5 |
|
323.15 |
-2.55 |
0.0003 |
-3.75 |
5.1692 |
-5.7357 |
0.995 |
110.19 |
1.65 |
aB0, B1, B2, B3 and B4 are parameters of C/ R-K model
Table 8 Parameters of the Jouyban-Acree model for tylosin in acetone(1- xc)+water (xc) solvents.
|
System |
A0 |
A1 |
A2 |
A3 |
A4 |
A5 |
|
Aectone+water |
267.6 |
-14032.2 |
-38.45 |
-279.91 |
14273.35 |
162.25 |
|
A6 |
A7 |
A8 |
R2 |
ARD |
RMSD |
|
|
-929 |
-368.21 |
40.69 |
0.994 |
56.46 |
2.54 |
aA0, A1, A2, A3 ,A4, A5, A6, A7 and A8 are parameters of Jouyban-Acree model.
Fig. 4 The measured and calculated mole fraction solubility of tylosin from the modified Apelblat model in pure solvents from at various temperatures.
Fig. 5 The measured and calculated mole fraction solubility of tylosin from the modified Apelblat model in acetone(1- xc)+water (xc) solvents from at various temperatures.
Fig. 6 The measured and calculated mole fraction solubility of tylosin from the C/R-K model in acetone(1- xc)+water (xc) solvents from at various temperatures.
Thermodynamic properties for the solution
The research of thermodynamic properties for dissolution process is necessary to analyzing and optimization design for industry application. ΔsolHo is defined as standard dissolution enthalpy, ΔsolSo is defined as standard dissolution entropy, and ΔsolGo is defined as standard dissolution Gibbs energy change. ΔsolHo, ΔsolSo and ΔsolGo of solution of tylosin dissolution process in different solvents can be calculated with Eq. (21), Eq. (22) and Eq. (23)24,25 by Gibbs-Duhem equation,Van¢t Hoff equation and modified Apelblat model. ζH and ζTS are defined as the comparison of the relative contribution of ΔsolHo and ΔsolSo to ΔsolGo in dissolution process process.26-30
where R is the universal gas constant (8.314 J·mol-1·K-1), three parameters of A, B and C are from modified Apelblat. T is 298.15 K.
Table 9 Thermodynamic functions relative to dissolution process of tylosin in pure solvents.
|
Systems |
△solHo |
△solSo |
△solGo |
ζH |
ζTS |
|||
|
kJ×mol-1 |
J×mol-1×K-1 |
kJ×mol-1 |
% |
% |
||||
|
Methanol+tylosin |
29.77 |
61.03 |
11.57 |
62.06 |
37.94 |
|||
|
Ethanol+tylosin |
30.60 |
67.37 |
10.51 |
60.37 |
39.63 |
|||
|
n-Propanol+tylosin |
14.34 |
18.61 |
8.79 |
72.09 |
27.91 |
|||
|
n-Butanol+tylosin |
25.44 |
54.92 |
9.07 |
60.84 |
39.16 |
|||
|
Chloroform+tylosin |
21.10 |
46.66 |
7.18 |
60.26 |
39.74 |
|||
|
Acetonitrile+tylosin |
7.78 |
3.79 |
6.65 |
87.33 |
12.67 |
|||
|
Butyl acetate+tylosin |
6.63 |
0.92 |
6.35 |
96.01 |
3.99 |
|||
|
Ethyl acetate +tylosin |
4.75 |
10.72 |
7.95 |
59.78 |
40.22 |
|||
|
Benzene+tylosin |
28.62 |
68.19 |
8.29 |
58.46 |
41.54 |
|||
|
Tetrahydrofuran+tylosin |
15.06 |
27.05 |
6.99 |
65.12 |
34.88 |
|||
aΔsolHo, ΔsolSo and ΔsolGo are the standard molar enthalpy, standard molar entropy and standard molar Gibbs energy change of solution of tylosin in different solvents;
The ζH and ζTS represent the comparison of the relative contribution to the standard Gibbs energy by enthalpy and entropy in the solution process, respectively.
Table 10 Thermodynamic functions relative to dissolution process of tylosin in acetone(1- xc)+water (xc) solvents.
|
Systems |
△solHo |
△solSo |
△solGo |
ζH |
ζTS |
|
kJ×mol-1 |
J×mol-1×K-1 |
kJ×mol-1 |
% |
% |
|
|
xc=0 |
18.65 |
36.40 |
7.80 |
63.22 |
36.78 |
|
xc=0.1955 |
16.64 |
29.05 |
7.98 |
65.77 |
34.23 |
|
xc=0.3629 |
14.30 |
20.53 |
8.18 |
70.03 |
29.97 |
|
xc=0.4466 |
12.17 |
12.43 |
8.46 |
76.65 |
23.35 |
|
xc=0.5182 |
13.19 |
14.18 |
8.96 |
75.72 |
24.28 |
|
xc=0.6827 |
12.66 |
6.07 |
10.85 |
87.5 |
12.5 |
|
xc=0.7634 |
13.29 |
5.30 |
11.71 |
89.36 |
10.64 |
|
xc=0.8288 |
15.14 |
9.93 |
12.18 |
83.65 |
16.35 |
|
xc=0.8827 |
16.31 |
6.14 |
14.47 |
89.9 |
10.1 |
|
xc=0.9281 |
-13.67 |
-104.99 |
17.63 |
30.4 |
69.6 |
|
xc=0.9667 |
-18.15 |
-127.48 |
19.86 |
32.32 |
67.68 |
|
xc=1 |
-27.61 |
-169.16 |
22.82 |
35.38 |
64.62 |
The values of ΔsolHo, ΔsolSo and ΔsolGo were listed in Tables 9 and 10 together with ζH and ζTS. It indicated that ΔsolHo, ΔsolSo and ΔsolGo values of tylosin dissolution process were all positive in solvents except for xc>0.8827 mixture solvents. ΔsolHo>0 proved that the dissolving process of tylosin in solvents was expressed as endothermic process. ΔsolSo>0 showed it was an entropy-drives in dissolving process of tylosin. Further, ζH > 0.55 showed that ΔsolHo was the main contributor to ΔsolGo during the dissolution. Otherwise, ζTS > 0.55 showed that ΔsolSo was the main contributor to ΔsolGo.
Conclusions
New experimental results for solubility of tylosin in different solvents were investigated at temperature from 279.75 to 323.15 K. It could be seen that the solubility of tylosin in chloroform was the highest and followed by butyl acetate, acetonitrile, tetrahydrofuran, acetone, benzene, n-butanol, ethyl acetate, n-propanol, ethanol, methanol and water. Solubility of tylosin gradually decreased with water increasing in water+acetone mixture solvents. Data fitting results showed the modified Apelblat model agreed litter better with experimental data thanVan¢t Hoff model, Wilson model NRTL model in pure solvents, and C/R-K model,Jouyban Acree model in acetone+water solvents according with ARD, RMSD and R2 .The calculated data of ΔsolHo, ΔsolSo, ΔsolGo, ζH and ζTS indicated that solution process of tylosin in solvents was expressed as endothermic process and an entropy-drives process. Dilution crystallization process will be selected to separate and purify for tylosin according with experimental results.
Conflict of interest
There are no conflicts to declare.
Acknowledgements
The work is financially supported by Project of Doctoral Fund in Henan University of Technology (2016BS025), Program for Science & Technology in Henan University of Technology (2017QNJH29, 2017RCJH09) and China Scholarship Council (CSC).
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