DOI:10.30919/esmm5f233

Received: 02 Apr 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: [email protected]

Zhanhu Guo    E-mail: [email protected]

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. Moreoverexperimental solubility increased with temperature increasing except for waterxc0.9281+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: TylosinSolubility; 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 xrepresent 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 andλ21 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).

References

1. J. M. McGuire, W. S. Boniece, C. E. Higgens, M. M. Hoehn,W. M. Stark, J. Westhead and R. N. Wolfe, Antibiotics and Chemotherapy, 1961, 11, 320-327.

2. H. A. Kirst, Progress in Medicinal Chemistry, 1994, 31, 265-295.

3. K. Kumar, S. C. Gupta , Y. Chander and A. K .SinghAdv. Agron., 2005, 87,1-54. 

4. Y. M. Shen, Z. F. Liu, T. Li and B. Z. RenJ. Chem. Thermodyn., 2015, 80, 128-134.

5. X. M. Jiang, Y. H. Hu, Z. B. Meng, W. G. Yang and F. ShenFluid Phase Equilib., 2013, 341, 7-11.

6. J. H. Hildebrand, J. M. Prausnitz and R. L. Scott, Regular and Related Solutions.Van Nostrand Reinhold Co., New York.1970.

7.Y. Li , F. A.Wang, L. Xu, H. Jin and B. Z. Ren, Fluid Phase Equilib., 2010, 298, 246-252.

8. R. L. Hamill, M. E.Haney, J. M. Mcguire and M. C. Stamper, US 3178341, 1965.

9. A. Apelblat and E. Manzurola, J. Chem. Thermodyn.,1997, 29, 1527-1533.

10. A. Apelblat and E. Manzurola, J. Chem. Thermodyn.,1999, 31, 85-91.

11. J. J. Zhi, Q. Liu, T. Li and B. Z. Ren, J. Chem. Eng. Data., 2016, 61, 2052−2061.

12. Y. M. Shen, Z. F. Liu, J. J. Zhi, T. Li and B. Z. Ren, J. Mol. Liq., 2015, 203, 131–136.

13. S. J. Han, Chemical Phase Equilibrium. Beijing: China Petrochemical Press, 1991.

14. F. A. Wang and Y. L. Jiang, Molecular Thermodynamics and Chromatographic Retention.Beijing : Meteorology Press, 2001.

15. G. M. Wilson, J. Am. Chem. Soc.,1964, 86, 127–130.

16. X. Z. Chen, Z. Y. Cai and W. M. Hu, Chemical Engineering Thermodynamics. Beijing : Chemical Industry Press, 2008.

17. H. Renon and J. M. Prausnitz, Ind. Eng. Chem. Process Des. Dev., 1969, 8, 413–419.

18. B. D. Souza, L. Keshavarz, R. R. E. Steendam, O. C. Dennehy, D. Lynch, S. G. Collins, H. A. Moynihan, A. R. Maguire and P. J. Frawley, J. Chem. Eng. Data., 2018, 63, 1419−1428.

19. W. E. Acree, JrThermochim. Acta.,1992, 198, 71–79.

20. A. Jouyban, J. Pharm. Sci., 2008, 11, 32-58.

21. D.Y. Li, H. X. Hao, B. B. Fang, N. Wang, Y. N. Zhou, X. Huang and Z. Wang, Fluid Phase Equilib., 2018, 461, 57-69.

22. H. Zhang, Z. K Liu, X. P. Huang and Q. Zhang, J. Chem. Eng. Data., 2018, 63, 233-245.

23. A. Jouyban, F. Martinez and W. E. Acree, Jr. J. Chem. Eng. Data., 2017, 62, 1153-1156. 

24. C. L. Zhang, F. A. Wang and Y. Wang, J. Chem. Eng. Data., 2007, 52, 1563–1566.

25. T. Li, Z. X. Jiang, F. X Chen and B. Z. Ren. Fluid. Phase. Equilibria.,2012, 333, 13-17.

26. G. Wang, Y. L.Wang, X. W. Hu, Y. G. Ma and H. X. Hao, Fluid. Phase. Equilibr., 2014, 361, 223-228.

27. X. Liu, Y. H. Hu, M. M. Liang,Y. L. Li, J. J. Yin and W. G. Yang, Fluid. Phase. Equilib., 2014, 367, 1-6.

28. H. Buchowski, A. Ksiazcak and S. Pietrzyk, J. Phys. Chem., 1980, 84, 975–979.

29. J. Fang, M. J. Zhang, P. P. Zhu, J. B. OuYang, J. B. Gong, W. Chen and F. X. Xu, J. Chem.Thermodyn., 85 (2015) 202–209.

30. C. Cheng, C. Yang, L. Meng, J. Wang, G. B. Yao and H. K. Zhao, J. Chem. Thermodyn.,97 (2016) 158–166.