Solubility measurement and thermodynamic properties of sulfamonomethoxine in pur

Yanmin Shen,Wenju Liu,Paifeng Shi,Chao Wang

School of Chemistry and Chemical Engineering,Henan University of Technology,Zhengzhou 450001,China

Keywords:Solubility Sulfamonomethoxine Sulfamonomethoxine hydrate Thermodynamic properties

ABSTRACT The experimental solubility of sulfamonomethoxine in six different pure solvents (methanol,ethanol,1-propanol,l-butanol,ethyl acetate and acetone) and sulfamonomethoxine hydrate in acetone+water mixture solvents were measured from 294.55 K to 362.15 K by a laser dynamic method under atmospheric pressure.Experimental results indicated that the solubility data of sulfamonomethoxine increased with temperature increasing in pure solvents and the solubility followed this order:acetone >methanol >ethanol >ethyl acetate >1-propanol >1-butanol,but solubility in ethyl acetate was not affected significantly by temperature.In acetone+water mixture solvent,the solubility of sulfamonomethoxine hydrate increased with temperature and the acetone concentration.Thermodynamic equations were applied to correlate solubility data of sulfamonomethoxine and sulfamonomethoxine hydrate including the modified Apelblat equation,λh equation,Wilson equation,NRTL equation,Van’t Hoff-Jouyban Acree equation and modified Apel-Jouyban-Acree equation.Furthermore,thermodynamic properties ΔGd, ΔHd and ΔSd of sulfamonomethoxine and sulfamonomethoxine hydrate in dissolution process were obtained and discussed with the modified Van’t Hoff equation and Gibbs equation.

1.Introduction

Sulfamonomethoxine(SMM,CAS No.1220-83-3,Fig.1) is a white or crystal powder,which is named 4-Amino-N-(6-methoxy-4-pyrimidinyl) benzenesulfonamide SMM is used to prevent diseases and deal with in livestock [1–4].Sulfamonomethoxine hydrate (SMMH) is sulfamonomethoxine derivative and more active antibiotics drug.In order to utilize better and separate from mixture solution,the solubility data of solid–liquid equation of sulfamonomethoxine is an essential and important parameter for choosing separation technology in application fields.But little solubility data for SMM and sulfamonomethoxine hydrate has been recorded from literature [5,6].

Fig.1.Structure of sulfamonomethoxine.

In this paper,experimental solubility data of sulfamonomethoxine in six pure solvents(methanol,ethanol,1-propanol,1-butanol,ethyl acetate and acetone) and sulfamonomethoxine hydrate in acetone+water mixture solvents were surveyed from 294.55 K to 362.15 K by a laser dynamic method under atmospheric pressure.Solubility data were correlated by different thermodynamic equations such as λh equation,modified Apelblat equation,NRTL(Non-Random Two Liquids) equation,Wilson equation,van’t Hoff-Jouyban Acree equation (van’t-J-A) and modified Apel-Jouyban-Acree equation(Apel-J-A).In addition,The thermodynamic parameters ΔGd,ΔHd,ΔSdof SMM and SMMH were investigated in dissolve process in chosen solvents.

2.Experimental

2.1.Materials

Sulfamonomethoxine hydrate (C11H12N4O3S.H2O,molecular weight 298.32 g∙mol-1),was gained from Daming Biotech.Co.Ltd.,China.The sulfamonomethoxine was obtained by heating sulfamonomethoxine hydrate at 120 °C for 4 h.The information of methanol,ethanol,1-propanol,l-butanol,acetone,ethyl acetate and acetone was listed in Table 1.

Table 1The source and mass fraction purity of chemicals

2.2.Thermal analysis

Melting point of sulfamonomethoxine hydrate and the water content was measured by a thermogravimetric analyzer instrument(model STA-449C)with the temperature from 20 to 500°C at a heating rate of 10 K.min-1under N2atmosphere(40 ml.min-1),the experiment were detected twice.

2.3.XRD analysis

The crystal of sulfamonomethoxine and sulfamonomethoxine hydrate was confirmed by XRD carried on Rigaku Mini Flex 600(Rigaku,Japan,).The XRD data were collected from 5° to 40° (2θ)at a scanning rate of 5(°).min-1under atmospheric pressure.

2.4.Solubility measurement

In this study,solubility of SMM in six pure solvents and SMMH in acetone+water mixture solvents under atmospheric pressure were measured with a laser dynamic method by the literature[7,8].The set of laser instruments is composed of a recorder,an optic-electric transformer and a laser generator.Measurement principal of a laser dynamic method is that light signal will change with degree of turbidity of solution,when the solute is dissolved completely in solution,the light signal reach maximum,solubility will be judged and measured in selected solvent at constant temperature.In this work,a 100 ml double jacketed glass vessel was adopted to measure solubility.First,about 30 ml solvent was added into jacketed glass vessel and controlled by circulating water for keeping constant temperature (±0.05 K),but also,condenser was equipped to prevent solvent loss.Then,a few excess sulfamonomethoxine hydrate(or sulfamonomethoxine)was added into in solvent and stirred continuously,heating rate was gradually slower within 0.05 K.min-1about with light signal changing amplitude,the light signal was the strongest passing the solvent when the solute was disappeared.At the moment,saturated solubility was obtained at this temperature and calculated through recording the mass of solute and solvent.Every solubility data was measured twice to ensure the accuracy.The solubility x in pure solvents and acetone+water solvent mixtures can be calculated by Eqs.(1) and (2),respectively.

In Eq.(1) m1and m2are the mass of SMM (or SMMH) and six pure solvents,respectively.M1and M2are the molecular weight of SMM (or SMMH) and six pure solvents,respectively.In Eq.(2)m1,m2,m3are the mass of SMM (or SMMH),acetone and water,respectively.M1,M2and M3are the molecular weight of SMM (or SMMH) acetone and water,respectively.

2.5.Hansen solubility parameter

Hansen solubility parameter (δt,(J.cm-3)1/2) is applied to explain and discuss the solubility behavior of solute in solvent or polymer,which is composed of three parts including Hansen dispersion solubility parameter (δd,(J.cm-3)1/2),polar solubility parameter(δp,(J.cm-3)1/2)and hydrogen bonding solubility parameter (δh,(J.cm-3)1/2),respectively.The values of δd,δpand δhwere incited from literature [9–11].The total δtin pure solvents is expressed into the following form.

In mixture solvents the total δtcan be calculated by

In Eq.(4),α represents the volume fraction of acetone in acetone+water mixtures,δ1and δ2are the solubility parameter of acetone and water,respectively.

3.Thermodynamic Equations

Thermodynamic equations were adopted to correlate solubility data of sulfamonomethoxine and sulfamonomethoxine hydrate to build new correlation model for widening solubility range for industry application and design.

3.1.Modified Apelblat equation

The modified Apelblat equation is adopted to correlate the relation between mole fraction solubility of solute and the experimental temperature in solid-liquid phase equilibrium.This semiempirical equation is expressed simply as the following form[12–14]:

In Eq.(5),x represents mole fraction solubility of the solute under the temperature T.A,B and C represent thermodynamic parameters.

3.2.Buchowski–Ksiazaczak λh equation

Buchowski et al found and proposed λh equation in 1986[15]at first.The equation was expressed with the following:

In Eq.(6),x represents mole fraction solubility of the solute at the temperature T;Tmstands for the melting temperature of SMM and was detected 481.15 K from Fig.2;λ and h represent thermodynamic model parameters.

3.3.Wilson equation

According to the thermodynamic theory of solid–liquid phase equilibrium,the relation between the activity coefficient γi,more fraction solubility x of the solute and temperature in solution can be arranged as following form [16–18].

In Eq.(7),Tmis melting point temperature 481.15 K;R is 8.314 J∙mol-1∙K-1,ΔfusH is the molar enthalpy of melting(-36.47 kJ∙mol-1) at Tmfrom Fig.2.The activity coefficient γ1,γ2are described by the Wilson model and given as following form[19].

Fig.2.(a) TG-DSC curve of sulfamonomethoxine.(b) TG-DSC curve of sulfamonomethoxine hydrate.

where V1and V2stand for the molar volumes of solute and pure solvent,cm3.mol-1.The values of V1and V2can obtained from the literature [20].The parameters of Δλ12and Δλ21represent the energy across interaction between molecules,J∙mol-1.

3.4.NRTL equation

The NRTL model was originally proposed by Renon and coworkers,which contained three adjustable parameters [21].It can be widely used both vapor–liquid and liquid–solid phase equilibrium[16,22].The activity coefficient in NRTL model is described the following form:

where Δgij(gij-gii)can be considered model constant and represent the energy across interaction between molecules,J∙mol-1.αijis inrespect of the nonrandomness of the solution with αij=αji.

3.5.Jouyban-acree equation

The Jouyban-acree equation is a relatively more universal model to describe the influence of temperature and solvent components on the solubility [23].It is defined as follows:

where xAis experimental determination solubility of SMMH in acetone+water mixtures.xBand xCrepresents initial mole fraction composition of acetone and water in mixture solvents with absence of SMMH,Siis a series of model parameters.ln(xA)Band ln(xA)Care the dissolution equilibrium solubility of SMMH in acetone and water pure solvent.

3.5.1.Modified Apel-Jouyban-Acree equation

ln(xA)Band ln(xA)Ccan be expressed with modified Apelblat model the following Eqs.(16) and (17).

The combination of Jouyban-Acree equation (15) and modified Apelblat model can be simplified to Eq.(18)[24–26]for binary solvent systems,i=2 and xC=1 -xB,

There are nine model parameters including D1,D2,D3,D4,D5,D6,D7,D8and D9,xBrepresents mole fraction of acetone in acetone+water mixture solvents with absence of SMMH.

3.5.2.van’t Hoff-Jouyban Acree equation

According to dealing with way of mentioned above,ln(xA)Band ln(xA)Ccould be also expressed with the van’t Hoff model as Eqs.(19) and (20) [16].

The combination of Jouyban-Acree equation(15)and van’t Hoff model can be simplified to Eq.(21) [24–26].

where C1,C2,C3,C4,C5,C6and C7are seven model parameters,xBrepresents mole fraction of acetone in acetone+water mixture solvents with absence of SMMH.

4.Results and Discussion

4.1.DSC and TG of sulfamonomethoxine and sulfamonomethoxine hydrate

The TG-DSC curves of the sulfamonomethoxine hydrate and sulfamonomethoxine were shown Fig.2 this curves indicated that mass loss started from 323.15 K and a large mass loss took place at about 473.15 K.It was explained that the first stage mass loss 5.70% should be the losses of the water molecules in hydrate because the water theoretical mass fraction content in sulfamonomethoxine hydrate is 6.04%.Determination content value was slightly lower than theoretical values probably because small water loss inside the apparatus at the original temperature under the nitrogen.In the DSC curve of hydrate,two endothermal peaks occurred at the temperature of 352.08 K and 481.15 K,respectively,it was inferred that 352.08 K was dehydration peak and 481.15 K was melting peak of sulfamonomethoxine and sulfamonomethoxine hydrate.The enthalpy of fusion(-36.47 kJ∙mol-1)of the initial material can be obtained by thermal analysis software.

4.2.XRD of sulfamonomethoxine and sulfamonomethoxine hydrate

The XRD data of sulfamonomethoxine in six pure solvents and sulfamonomethoxine hydrate in acetone+water was determined and displayed in Fig.3.It can be seen easily that sulfamonomethoxine and sulfamonomethoxine hydrate had different crystal pattern.Sulfamonomethoxine hydrate from acetone+water in selected system had the same identical characteristic peaks the same as the raw material of sulfamonomethoxine hydrate,and sulfamonomethoxine in six pure solvents did not happen crystalline transformation from Fig.3.

Fig.3.Powder x-ray diffraction patterns of SMM in different organic solvents and SMMH in acetone+water:(a) SMMH;(b) SMMH from acetone+water;(c)sulfamonomethoxine;(d) SMM from methanol;(e) SMM from ethanol;(f) SMM from 1-propanol;(g) SMM from 1-butanol;(h) SMM from acetone;(k) SMM from ethyl acetone;

4.3.Solubility data in different solvents

Solubility of sulfamonomethoxine in methanol,ethanol,1-propanol,l-butanol,ethyl acetate,acetone and the solubility of sulfamonomethoxine hydrate in acetone+water mixtures were listed in Tables 2 and 3 and graphically plotted in Figs.4 and 5.It was shown from Fig.4,experiment results indicated the solubility data of sulfamonomethoxine in six selected solvents increased with increasing temperature.Within the temperature range,the solubility followed the order acetone >methanol >ethanol >ethyl acetate>1-propanol>1-butanol except for ethyl acetate,solubility decreased with the number of carbon atoms increasing.Solubility of sulfamonomethoxine varying range in ethyl acetate changed little with the temperature increasing because of possibly a more considerable ordering of ethyl acetate molecules [27].According to Hansen Solubility Parameters(HSP),the order of the total polarity is water>methanol>ethanol>1-propanol>1-butanol>aceto ne>ethyl acetate,but solubility of sulfamonomethoxine disagreed with this regularity.It indicated that solubility of sulfamonomethoxine was not a directly relation between the solubility order and the polarity of selected solvents.From Fig.1,it can be seen that sulfamonomethoxine is composed of several radical groups:-C=O,-NH2,-C=N and -S=O.According to the likedissolves-like theory [9–11],sulfamonomethoxine in acetone has higher solubility than other solvents.The solubility of sulfamonomethoxine hydrate in acetone+water was shown in Fig.5.At constant temperature,the solubility increased rapidly with acetone concentration increasing and with HSP values decreasing from Table 4.At constant acetone concentration,the solubility of sulfamonomethoxine hydrate in acetone+water mixtures increased with increasing temperature range from 298.75 K to 322.65 K from Table 3 and Fig.5.

Table 2Mole fraction solubility of sulfamonomethoxine in different solvents at pressure 101.3 kPa.

4.4.Solubility correlation

The experimental solubility of sulfamonomethoxine in different pure solvents was correlated by the modified Apelblat equation,λh equation,Wilson equation and NRTL equation.The experimental solubility of sulfamonomethoxine hydrate in acetone+water mixtures was correlated by modified Apelblat equation,λh equation,van’t Hoff-Jouyban Acree Equation and Modified Apel-Jouyban-Acree Equation.According to evaluating the accuracy and prediction ability of the correlated methods,RD,RAD and RMSD were applied and were calculated with Eqs.(22)–(24) [24,13].

where N is the number of experimental points,is calculated solubility,is the experimental solubility.RD means relative error,RAD is named corresponding average absolute deviation,and RMSD is named root mean square deviations.

The solubility of sulfamonomethoxine in the pure solvents was correlated by the modified Apelblat equation,λh equation,Wilson equation and NRTL equation.From Tables 2 and 5,it can be observed and compared that the values of RAD and RMSD among four equations,the order on total average values of RAD was 9.78% (Wilson) >5.43%(Apel) >4.88%(λh) >1.7%(NRTL),and the order on total average values of 105RMSD among pure solvents:37.34 (Wilson) >7.84(λh) >6.24 (Apel) >3.69 (NRTL).Values of RAD and RMSD from NRTL were smaller than those of modified Apelblat equation,λh equation,Wilson equation.These data indicated NRTL equation agreed better with solubility data of SMM according to temperature range from 294.55 K to 362.15 K in elected solvents.

The solubility of sulfamonomethoxine hydrate in acetone+water mixture solvents was fitted by the modified Apelblat equation,λh equation,the van’t Hoff-Jouyban Acree equation and the modified Apel-Jouyban-Acree equation.From Tables 3 and 6,It can be observed that the order on total average values of RAD was 4.66%(λh) >4.18%(Apel-J-A) >3.87%(Apel) >2.86% (van’t-J-A),and the order on total average values of 105RMSD among mixture solvents was λh (1.19) >van’t -J-A (0.97) >Apel-J-A (0.65) >Apel(0.57).The values of RAD and RMSD evaluated by modified Apelblat equation were less than other three equations.These data indicated modified Apelblat equation agreed better with solubility data of SMMH according to temperature range from 298.75 K and 322.65.15 K in mixture solvents.

Table 3Mole fraction solubility of sulfamonomethoxine hydrate in acetone(xB)+water (1-xB) at pressure 101.3 kPa.

Table 4Hansen solubility parameters (HSP) of pure solvents① and mixture solvents②

Table 5Parameters of four equations for SMM in pure solvents

Table 6Parameters of equations on SMMH in acetone(xB)+water (1-xB) mixtures

Fig.4.Mole fraction solubility x of SMM and calculated values from NRTL model in pure solvents,the solid lines represent the calculated values.

Fig.5.Mole fraction solubility x of SMMH and calculated values from modified Apelblat equation in acetone(xB)+water(1-xB) binary mixtures,the solid lines represent the calculated values.

5.Thermodynamic Properties for Dissolving Process

Thermodynamic properties of solid–liquid phase equilibrium on sulfamonomethoxine and sulfamonomethoxine hydrate dissolution process play an important role in producing and application in drugs.In this work,thermodynamic properties enthalpy and entropy of sulfamonomethoxine and sulfamonomethoxine hydrate were deduced and discussed by van’t Hoff-equation [28] with according literature [18,28,29].

where ΔGd,ΔHdand ΔSdstand for Gibbs free energy,enthalpy of dissolution and entropy of dissolution and x is the mole fraction solubility of solute.n is the number of experiment.Thmrepresents mean of all experimental temperature.

The plot of lnx1verse (1/T-1/Thm) for different systems were shown in Figs.6 and 7.The ΔHdand ΔSddissolution of sulfamonomethoxine and sulfamonomethoxine hydrate were obtained from the slope and the interception with y-axis of the resulting trend line.The ΔGdvalues of solution can be calculated from Eqs.(26)and(27)[26].In order to explain ΔHdand ΔSdaffecting to ΔGdin dissolution process on SMM and SMMH,relative contribution to ΔGdof ΔHd(ζH)and ΔSd(ζTS)were calculated by Eqs.(29)and(30)respectively[30].

Fig.6.The plots of lnx versus (1/T-1/Thm) for SMM in pure solvents.

Fig.7.The plots of lnx versus (1/T-1/Thm) for SMMH in acetone(xB)+water(1-xB)mixtures.

From Table 7,it were shown that the values of ΔHdof SMM in pure solvent changed from 15.2 kJ∙mol-1to 60.26 kJ∙mol-1,and ΔSdof dissolution varied from -14.1 J∙mol-1∙K-1to 121.99 J∙mol-1∙K-1.The values of ΔHdand ΔSdof SMMH in acetone+water mixtures varied from 44.83 kJ∙mol-1to 49.84 kJ∙mol-1and from 74.68 J∙mol-1∙K-1to 84.29 J∙mol-1∙K-1,respectively.These data indicated that positive values of ΔHdin chosen solvents illustrated dissolution process of SMM and SMMH is always endothermic behavior,the negative values of ΔSdin ethyl acetate indicated that the solvent molecules hindered the dissolution process possibly [27].The positive values of the molar Gibbs free energy ΔGdin elected solvents showed that the dissolution process of SMM in organic solvents and SMMH hydrate in acetone+water mixture were not spontaneous.Moreover,calculated results from Table 7 indicated that ΔHdaffected with ΔGdmore than ΔSdbecause values of ζHwere higher than ζTSfor dissolution process of SMM and SMMH hydrate in discussed solvents.

Table 7Thermodynamic properties on dissolution enthalpy,entropy and Gibbs energy of SMM and SMMH in all solvents

6.Conclusions

The solubility data of SMM in six organic solvents and SMMH in acetone+water mixture solvents were studied and discussed at temperature ranging from 294.55 K to 362.15 K by laser monitoring techniques.The results illustrated that solubility data of SMM and SMMH was affected with temperature obviously,and increased with temperature increasing.But also solubility of SMMH decreased with water concentration increasing in acetone+water mixture solvents.Thermodynamic equation of modified Apelblat equation,λh equation,Wilson equation,NRTL equation,the van’t Hoff-Jouyban Acree equation and the modified Apel-Jouyban-Acree equation were applied to correlate the solubility,and the NRTL equation was more suitable in pure solvents,modified Apelblat equation agreed better in mixture solvents through comparing RAD and RMSD.Moreover,Thermodynamic properties ΔGd,ΔHdand ΔSdfor dissolving process of SMM and SMMH were calculated and analyzed by correlating the solubility and temperature.According to the thermodynamic data,dissolution process of SMM and SMMH is endothermic and not spontaneous respectively,and ΔHdplayed an important role in the molar Gibbs free energy ΔGd.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors would like to thank the Doctoral Foundation of Henan University of Technology in China(2016BS025),the Science Foundation of Henan University of Technology in China(2017RCJH09,2017QNJH29),Science Foundation of Henan Province in China(202102310208)for their financial assistance in this project.