Marzia Rahman ,Md.Anamul Hoque ,*,Mohammed Abdullah Khan ,Malik Abdul Rub ,Abdullah M.Asiri

1 Department of Chemistry,Jahangirnagar University,Savar,Dhaka 1342,Bangladesh

2 Chemistry Department,Faculty of Science,King Abdulaziz University,Jeddah 21589,Saudi Arabia

3 Center of Excellence for Advanced Materials Research,King Abdulaziz University,Jeddah 21589,Saudi Arabia

1.Introduction

Surfactants form aggregates in aqueous as well as in non-aqueous solutions beyond a certain concentration called micelles and this required concentration for this phenomenon is known as critical micelle concentration(cmc)and has been found various applications in different fields(basic as well as industrial purposes)[1-5].The insertion of additives into micelles of amphiphiles will influence its physicochemical characteristics,for example,the degree of dissociation,reaction rates as well as phase separation[1,6-9].Surfactants have diverse uses in various fields such as it is widely used in practical and industrial formulations as solubilizers,emulsifiers and detergents[10-12].Nonionic surfactants are used in cloud point separation of various unwanted materials from substrates[10].

Akin to the majority of the ethylene oxide(EO)derived compounds,TX-100 also shows contrary solubility features and precipitate/phase separation by means of a rise in temperature of the systems.The temperature at which clouding takes place is notorious as the cloud point(CP)of the amphiphile[13].The mechanism of phase separation means CP in nonionic surfactants is still not very understandable and keeps on to be a resource of argument amid diverse researchers.However,in the case of ionic surfactant under special conditions,the phase separation happening is described in terms of enhanced hydrophobic interactions,the dehydration of the hydrophilic part,as well as the formation of large associates[14].At CP the single-phase micellar solution is transform into surfactant-wealthy and surfactant-scanty phases.The convenient significance of the CP lies in the truth that emulsions,suspensions,ointments as well as foams stabilized in the company of nonionic surfactants happen to unstabilize while heated in the vicinity of the CP,e.g.,for the duration of manufacturing,steam sterilization,or several end uses[15,16].Additionally,amid a variety of surfactants,nonionic surfactants are chemically more effective molecular species in comparison to other nature of surfactant that are suitable and essential as excipients utilized in the pharmaceutical formulations as well as drug delivery[17,18].Usually nonionic surfactants are biodegradable,less toxic,higher stability as well as mild in nature and it form micelles in very dilute solution.They are also employed to assist solubilization as well as to improve the drug carrier emulsion stability[1].

The phase separation phenomenon in nonionic surfactant is sturdily influenced by the attendance of a variety of additives and therefore altering the atmosphere of the micelle[19,20].The emergence of clouding in the aqueous medium along with its partition into two phases commences assured shortcomings in its employment.Knowledge of CP of nonionic surfactants is important because formulations at temperatures considerably more than the cloud point possibly will lead to phase separation as well as instable state.It is reported that nonionic surfactant is highly effective near and below CP of that surfactant[21].Therefore,it is of vital importance to determine the outcome of different additives on the phase separation of nonionic surfactants.

Hoqueet al.[22]earlier studied the phase separation behavior of TX-100 in the absence as well as in the attendance of various organic additives in addition also evaluated their thermodynamic parameters.The CP value of 1.55 × 10-2mol·kg-1of TX-100 is found to be 336.85 K in aqueous system.Mudawadkaret al.[23]studied the clouding and thermodynamic properties of pure TX-100 and in the presence of different poly vinylpyrrolidone(PVP).Mudawadkaret al.obtained that cloud pointenhances slightly from336 Kto 340 K by means of a rise in TX-100 concentration from 1 wt%to 10 wt%.The change in cloud point of TX-100 has been accounted very slowly with change in concentration of surfactant[24].Bhattet al.[10]also reported phase separation behavior of ionic liquids and surfactant mixtures and also determine various possible thermodynamic parameters.Alauddinet al.[25]evaluated the CP of TX-100 in the attendance of alkanes and alcohols.Mahajanet al.[26]also deliberated the effect of various alcohols and ammines as well as inorganic salts on CP of TX-100 micelle solution.Cloud point of 1%TX-100 was found to be 339.1 K which is in fine conformity with the CP values observed by Rakshitet al.[27].Panchalet al.[28]investigated the cloud point of pure TX-100 as well as their mixture with sodium dodecyl sulfate(SDS)in the absence and presence of inorganic salts and found that the SDS enhances the CP of TX-100.Furthermore the presence of inorganic salts lessens the rise in cloud point.Recently,we have determined the cloud point and thermodynamic parameters of Tween 80 nonionic surfactant in the absence and presence of various electrolytes and polymers[29]and also evaluated the CP of TX-100 micelles in aqueous medium as well as in the attendance of diols/polyols[22].Although literature surveys[10,12,18,19,30,31]expose a lot of literatures on phase separation behavior of surfactants,a specific research regarding novel model systems is still required.

CFT is a third-generation cephalosporin antibiotic drug and has a wide ranging spectrum of activity which contains both gram positive as well as gram negative aerobic along with anaerobic bacteria[32].The two chief uses of such drugs are treating bacterial infection and stopping infection for the duration of surgery.CFT has been employed to take care of dissimilar bacterial infections for example respiratory tract infection,bone infection,joint infection,middle ear infection,and urinary tract infection.

Triton X-100(TX-100)is a nonionic surfactant and emulsifier which has no antimicrobial properties.It is treated as a comparatively mild detergent,non-denaturing and has been reported as a routine reagent in numerous references.It has been utilized in immunofluorescent microscopic studies,for staining flat-mount retinas and to estimate the lipase activity in post-heparin plasma as well as used in biochemical applications to solubilize proteins[33-36].

Keeping all above truths in view,in the current work we have evaluated the cloud point of the non-ionic surfactant TX-100(Scheme 1),in aqueous micellar solution in the absence as well as attendance of a(CFT)/(CFT+different inorganic salts).In addition to cloud point measurements,various related thermodynamic parameters for example free energyclouding were also evaluated and discussed in detail.

Scheme 1.Molecular model of Triton X-100(TX-100)(n=9-10).

2.Materials and Methods

TX-100(purity 0.98-1.00 in mass fraction,CAS Registry number 9002-93-1,molecular weight=647 g·mol-1)was purchased from Merck,Germany and utilized without any additional purification.Drug CFT(purity＞0.9956 in mass fraction,CAS Registry number 104376-79-6,molecular weight=661.6 g·mol-1)is provided by General Pharmaceutical Ltd.,Bangladesh;sodium chloride(purity 0.99 in mass fraction,CAS Registry number 7647-14-5,molecular weight=58.44 g·mol-1)from Merck,Mumbai India;sodium sulfate(purity 0.99 in mass fraction,CAS Registry number 7757-82-6,molecular weight=142.04 g·mol-1)from Merck,Mumbai,India;sodium carbonate(purity＞0.995 in mass fraction,CAS Registry number 497-19-8,molecular weight=105.99 g·mol-1)from Merck,Mumbai,India;potassium chloride(purity＞0.99 in mass fraction,CAS Registry number 7447-40-57,molecular weight=74.55 g·mol-1)from Merck,Mumbai India;potassium sulfate(purity＞0.99 in mass fraction,CAS Registry number 7778-80-5,molecular weight=174.26 g·mol-1)from Merck,Mumbai,India;potassium carbonate(purity＞0.995 in mass fraction,CAS Registry number 584-08-7,molecular weight=138.205 g·mol-1)from Merck,Mumbai,India;ammonium chloride(purity 0.985 in mass fraction,CAS Registry number12125-02-9,molecular weight=53.49 g·mol-1)from China;Ammonium sulfate(purity 0.99 in mass fraction,CAS Registry number 7783-20-2,molecular weight=132.14 g·mol-1)from Merck,Mumbai,India and ammonium carbonate(purity＞0.995 in mass fraction,CAS Registry number 506-87-6,molecular weight=96.09 g·mol-1)from Merck,Mumbai,India were employed as collected.De-ionized double-distilled water was employed to formulate the solutions of the TX-100 in the absence/attendance of drug/(drug+salts).TX-100 is soluble in all proportions in aqueous medium at 298.15 K(room temperature)means it is easily or freely soluble in aqueous solution at least 5 times of used concentration of current studied system.The specific conductivity of the water used throughout the experiment was 1.5-1.8 × 10-6S·cm-1at 298.15 K.

All cloud point/phase separation was achieved by placing Pyrex glass tubes(enclosing surfactant solution(TX-100))into a temperature controlled bath and the temperature was increased at the rate of 0.1 K per minute close to the cloud point and commencement of phase separation was noted by visual assessment.The temperature at which the phase separation starts was considered as cloud point following the method accounted in the literature[29,37,38].The same procedure was replicated at least three times.The mean temperatures of emergence and disappearance of clouding were considered as the CP.Akin procedures were adopted in the case of TX-100 in the presence of drug or(drug+salts)mixtures.The reproducibility of cloud point value was within±0.1 K.

3.Results and Discussion

3.1.Effect of drug or(drug+salts)on the CP of Triton X-100(TX-100)

Micelle size,micelle aggregation number,and clouding are significant outcomes for any surfactant system.Herein,the cloud point measurements of the concentration of TX-100(non-ionic surfactant)were always kept above the critical micelle concentration(cmc)values,which means,the TX-100 must be present in the micellar form[4].The concentration of surfactant was decided on the basis of theircmcvalues,not on the basis of their cloud point in pure form.A large number of additives of diverse nature and properties were analyzed at different concentrations to ensure the stability or clouding behavior of TX-100 by the deviation in temperature.In the present study,the additives employed were the drug(CFT),and various inorganic salts[NaCl,Na2CO3,Na2SO4,KCl,K2CO3,K2SO4,NH4Cl,(NH4)2CO3and(NH4)2SO4].Phase separation is an energetically controlled process,therefore,the knowledge of the effect of various additives(which may be used as a pharmaceutical ingredient)on clouding behavior of TX-100 is necessary for their application point of view.The EO of a non-ionic surfactant leans on the cooperation amid the hydrophilic as well as hydrophobic interactions and is extremely hypersensitive to the attendance of additives[39].

In the case of TX-100 as the temperature rises clouding takes place owing to thermal movement of H2O molecules that influence interaction or solvation of micelles.As a result,with rising temperature micelles initiate to interact with each another ensuing in a micellar network[40].The CP of the solutions of TX-100 in aqueous medium was evaluated at different concentrations(1×10-3to 10×10-3mol·kg-1)of TX-100 and their values are reported in Table 1.In our case,the cloud point value of 1.02 × 10-3mol·kg-1TX-100 in aqueous solution was obtained 339.55 K.Hoqueet al.obtained the cloud point values of 336.85 K for 1.55 × 10-2mol·kg-1of TX-100 in aqueous solution in earlier[22].Another researcher Mudawadkaret al.[23]observed that cloud point values of TX-100 enhance slowly from 336 to 340 K with an increase in the concentration of TX-100 from 1wt%to 10 wt%.Actually,the cloud point of this non-ionic surfactant has been accounted to change very slowly with an increase in concentration[24].

Table 1 Values of cloud point temperatures(T CP)for pure TX-100 in water①

Alauddinet al.[25]reported the CP of 1 wt%TX-100 was around 336.7 K in aqueous solution and Mahajanet al.[26]reported the cloud point of the same surfactant 339.1 K which means it is easy to say that our results are also in good conformity with the earlier literature values[25,27].There are two key causes why we require being aware of as well as managing the phase separation occurrence: first of all,for the reason that significant benefits have been obtained from the application of this phenomenon to a number of extraction as well as separation machinery.The second one is that application of clouding phenomena for certain purposes can unwillingly have an effect on the activity of a surfactant supported formulation and should thus be avoided.

The phase separation of any concentration of TX-100 solution in aqueous solution is probably owing to the large rise in aggregation number(Nagg)of surfactant micelles along with a reduction in intermicellar repulsion,ensuing from reduced dehydration of oxyethylene oxygens in the polyoxyethylene hydrophilic part by means of enhancing in temperature.The rise inNaggtogether with a reduction in intermicellar interaction generates huge micellar associates at that temperature in solution,that turns out to be clearly cloudy and two liquid phases appear separately[27].As we increase the concentration of TX-100 in solution the cloud point of the system also increases but slowly showing that spherical micelles increase in size as well as the shape changeover also takes place from spherical to disc shape at higher concentration of TX-100[40].This phenomenon increases the surface area of micelles ensuing a decreased dehydration by this means the increase of the CP of the solution takes place.

The effect of the addition of drug such as CFT on the CP values of TX-100 was examined in this study.The CP values of 2.02 × 10-3mol·kg-1,6.03 × 10-3mol·kg-1and 10.03 × 10-3mol·kg-1of TX-100 solutions enclosing different concentrations of the drug are revealed in Fig.1 and Table S1(Supporting Information).The CP values of TX-100 solutions were found to decrease as the concentrations of CFT increase.The decrease in CP of Triton X-100 due to the attendance of drug is due to the possibility of the elimination of water from TX-100 as well as the water which are nearby the surfactant.This phenomenon facilitates the micelles of TX-100 to get nearer with each other resulting in the decrease of cloud point of studied TX-100 and further decrease of the cloud point as the concentration of CFT increased.

Fig.1.Plot of T CP vs concentration of CFT for(■)1.998×10-3,(●)6.02×10-3 and(▲)10.01 × 10-3 mol·kg-1 TX-100 solution.

The CP of the aqueous solution of the employed surfactant is not likely to vary considerably if additive molecules do not produce a change in the characteristics of micelles either by micellar growth or by varying the hydration of surfactant micelles.The effect of different salts such as NaCl,Na2CO3,Na2SO4,KCl,K2CO3,K2SO4,(NH4)Cl,(NH4)2CO3and(NH4)2SO4on the CP of 6.03 × 10-3mol·kg-1and 10.01× 10-3mol·kg-1solutions of Triton X-100 in the attendance of 2.04× 10-3mol·kg-1drug was also examined and their achieved outcome is shown in Figs.2-4 and in Tables S2-S4(Supporting Information).TX-100 concentration in the aqueous phase reduces upon the addition of different salts owing to the salting-out effect.Actually,the salt is present in both the micellar as well as the aqueous phases.In addition,all measured salt concentrations did not go beyond their water solubility.Therefore,no formation of solid phase takes place.It is well known that the addition of certain inorganic compounds may lower the cloud point and hence the electrostatic interaction between the salt and the H2O molecule is higher compared to the hydrogen bonds in the polar head of surfactant and H2O.In the presence of inorganic salts used in the present study the cloud point of the system decreases[41].The outcome of the effect of salts(anionic counterion,concentration varies from 0.00103 to 0.201 mol·kg-1)in reducing CP values was obtained to be in the following order:NaCO3＞Na2SO4＞NaCl;K2SO4＞KCO3＞KCl and(NH4)2SO4＞Na2CO3＞NH4Cl.

The outcome of cationic co-ions in decreasing the cloud point of TX-100 and drug mixed systems is obtained the following sequence:NaCl＞KCl＞NH4Cl,Na2SO4＞K2SO4＞(NH4)2SO4and Na2CO3＞K2CO3＞(NH4)2CO3.The addition of inorganic salts in surfactant system is useful when the low-temperature surface activity of surfactants is needed to be enhanced.In addition,the surfactant and salt mixture is important when a surfactant is required to be employed at temperatures beyond its CP[37].Na2SO4is more effective in reducing the CP of TX-100 in comparison to NaCl,which is also accounted in earlier literature[42].Above result might be due to the nature of charge which decides the total the effect on cloud point of surfactant.The akin behavior of decrease in cloud point value of TX-100 by NaCl was also obtained by Heusch[43].

Fig.2.Plot of cloud point(CP)vs concentrations of sodium salts of(■)6.02 × 10-3 mol·kg-1 and(●)10.01 × 10-3 mol·kg-1 Tween-80 solution for(CFT+TX 100)systems.

In the Hofmeister series to explain the position of the ions two mechanisms have been proposed[38].Generally,the mechanism engaged was assumed to be associated with the ability of the ions to change the hydrogen bonding ability of water.

Ions which occur on the left side of the Hofmeister series(such as)are water structure makers which induce loss of entropy and immobilize water molecules.The addition of salts in solution produced the salting-out effect.During the salting-out effect,the H2O molecules are attracted to the electrolyte ions.The H2O molecules interacted with the hydrophilic portion of surfactant attract to the salt ions as well as the hydrophobic effect amid surfactant molecules enhances.Therefore,the addition of salts to the surfactant system reduced the values of cloud point.Salt ions which are found on the right side of the Hofmeister series are water structure breakers and these ions have high polariz ability which leads to the disruption of self-aggregated H2O molecules.Water structure breaker ions liberate more water molecules that are able to form hydrogen bonds with the ether groups of the surfactant;in that way,a salting-in effect happens.In the alternative mechanism,recently approved that,the ion effects are based on the direct ion-surfactant interaction in comparison to water structure changes by addition of salts in surfactant systems.

The attendance of salts supports the dehydration of TX-100 lessening interactions amid surfactant and water molecules.Since the water molecules enclose the salt ions,solute-solute interactions are enhanced and nonionic surfactant molecules form precipitation.In the case of the Na+,K+orsalts an electrolyte enclosing divalent anion is more efficient at salting-out the hydrophobic chain due to their higher charge density in comparison to those holding monovalent anions.The salting-out outcome causes the decreased solubility of Triton X-100.Energy is needed to rupture the interactions between the surfactant and the H2O molecules neighboring them.Cation efficiency in reducing the CP of utilized surfactant is in the following order:Na+＞K+＞NH4+.

3.2.Thermodynamics of clouding phenomenon

The entire physicochemical progressions are energetically controlled.The spontaneous micelle formation is noticeably directed by thermodynamic theories.The various thermodynamic parameters of the nonionic surfactant were evaluated by means of the cloud point values at phase separation.The thermodynamic parametersi.e.,standard free energy(),enthalpy()and entropy()change of the phase separation phenomenon were computed taking into account the solubility limitat the CP temperature by the phase separation model

Fig.3.Plot of cloud point(CP)vs concentrations of potassium salts of(■)6.02 × 10-3 mol·kg-1 and(●)10.01 × 10-3 mol·kg-1 Tween-80 solution for(CFT+TX-100)systems.

by means of the subsequent equation[10,22,38,40,44]

whereXsis the mole fraction of salts in surfactant mixture,Ris the gas constant andTis the taken cloud point temperature values in Kelvin scale.

The cloud point dependence onXs,the mole fractional solubility of the solute,can be stated as a symmetrical parabolic curve leading to Eq.(4)[45]

In Eq.(4)A,BandCare the constants and evaluated by the regression analysis of least squares.A representation of the parabolic curve for the plot of lnXsvs T(CP)to evaluate the enthalpy change(ΔHcϴ)of phase separation phenomena is revealed in Fig.5.

The lnXsversus Tplots are exposed in Figs.S2-S19(Supporting Information)and obtained to be nonlinear in all other studied systems.The constantA,BandCvalues are given in Table S5(Supporting Information).

The enthalpy of phase separation is then evaluated mathematically by substituting Eq.(4)into Eq.(2):

In aqueous solution,the values of various thermodynamic parameters in the case of pure Triton X-100 are shown in Table 2.The values of Δare found to be positive which denotes that the clouding phenomenon is nonspontaneous in nature.The positive Δvalues are found to lessen with the enrichment of concentration of TX-100 in aqueous solution.The emergence of phase separation in the solution of the surfactant is owing to the enhanced desolvation of hydrophilic portions of the surfactant.In view of the fact that the H2O molecules get effortlessly separated from the micelles and isolate from the solution,hence,phase separation is detected and can be regarded as the limit of solubility[46].

Accordingly,the clouding constituents attain the highest solubility at the cloud point and,consequently,the Δallied with the clouding phenomena showing that phases change to occur from a homogeneous to a heterogeneous phase.Both the values of Δand Δare for pure surfactant obtained to be positive at almost all concentration of TX-100 as well as their value regularly decreases with an increase in the concentration of TX-100 and they change into negative at higher concentration of surfactant.The occurrence of both enthalpy as well as entropy in positive sign is the feature of hydrophobic bonding while the negative sign of both values is the feature of hydrogen bonding along with electrostatic interactions[47].The occurrence of negative values of ΔHcand Δindicates that the phase separation phenomenon is guided completely by only enthalpy involvement.

Fig.4.Plot of cloud point(CP)vs concentrations of ammonium salts of(■)6.02 × 10-3 mol·kg-1 and(●)10.01 × 10-3 mol·kg-1 Tween-80 solution for(CFT+TX-100)systems.

Fig.5.Plot of ln X s vs T of 6.02 × 10-3 mol·TX-100 solution in the presence of 1.998× 10-3 mol·kg-1 CFT to calculate.

In the case of CFT drug and Triton X-100(2.02×10-3,6.03×10-3,10.03 × 10-3mol·kg-1)mixture in water,the value ofΔwas obtained to be positive showing that the clouding phenomena are non-spontaneous in nature.In all the cases,the values of Δwere decreased by means of the increase in the concentration of the drug,which showed that the clouding is inclined to shift in the direction of spontaneityviathe rise of the concentration of the drug.The values of Δand Δwere obtained to be negative forall mixed systems of drug and surfactant in different compositions and their values decrease with enhancing of drug concentration.The negative Δvalues are indicative ofan exothermic reaction.These types of the trend of ΔHcand Δwere also previously obtained in the case of clouding phenomena of nonionic surfactant in the absence and presence of electrolyte[48].Rubet al.[49-51]obtained the negative values of Δand Δfor some amphiphilic drugs in the attendance of Tween 80 and also other additive mixtures.Kabir-ud-Dinet al.[52]also observed negative values of ΔHcandfor the promethazine hydrochloride(PMT)-Tween 80 mixed system.

The different thermodynamic parameters were also determined in the presence of different natures of salts(sodium,potassium,and ammonium)in the mixture of TX-100 and drug solutions and their values are shown in Tables 3-5 and Tables S6-S9(Supporting Information).Inthe presence of different concentrations of salts(NaCl,Na2SO4,Na2CO3,KCl,K2SO4,K2CO3,NH4Cl,(NH4)2SO4,(NH4)2CO3)in the mixed system of TX-100(6.05 × 10-3and 10.01 × 10-3mol·kg-1)and CFT having 2.01 × 10-3mol·kg-1concentration the Δvalues are obtained to be positive signifying the clouding phenomena are also nonspontaneous in the attendance of salts and their positive value decreases with enhanced salt concentration which points out that this phenomenon has a propensity to progress toward spontaneity with the enhancement of concentration of salt.However,the values of Δand Δare found to be negative for both concentrations of TX-100 solutions keeping 2.05 × 10-3mol·kg-1drug at almost all concentration(except highest concentration with few exception)of every salt and their negative values decrease regularly by means of the enhancement of concentration of salts but at highest concentration of salts their value changes into positive value in almost all systems(Tables 3-5 and S6-S9(supplementary materials)).In the presence of salts,the behavior or trend of the change of ΔHcand Δvalues was obtained to be approximately akin in all studied systems.The obtained negative value of Δprobably will happen when the hydration of H2O molecules in the region of the hydrophilic head portion happen to more considerable as compared to the ruin of the H2O structure in the region of the hydrophobic alkyl chains of monomers of surfactants[22,53,54].The obtained results pictured that the values of Δwere directed by mutually ΔHcand Δat the phase separation of TX-100 in the occurrence of salts.

Table 2 Values of thermodynamic parameters of clouding process for pure TX-100 in water①

Table 3 Values of thermodynamic parameters of clouding of 2.02 × 10-3 mol·kg-1,6.03 × 10-3 mol·kg-1,10.03 × 10-3 mol·kg-1 TX-100 and varying concentration of CFT in water medium①

Table 5 Values of thermodynamic parameters of clouding of 10.01 × 10-3 mol·kg-1 TX-100 and 2.04 × 10-3 mol·kg-1 CFT in(water+salt)medium①

The occurrence of positive Δvalues is due to the disorders of H2O structure round about the hydrophobic alkyl parts of surfactant monomers[55].The negative Δvalues also denote the importance of London dispersion forces as an attractive force of association of the amphiphile system[56,57]while the occurrence of positive values ofdenotes the destructing of ordered H2O round about the hydrophobic parts of the amphiphiles[58-62].

The free energy of transfer(Δ)of phase separation of surfactant from the aqueous medium to the solution having additives is attained by way of Eq.(6)[63]

In the case of cloud point of the TX-100 and CFT mixed system,free energy of transfer(Δwas found to be positive for 6.03× 10-3and 10.03 × 10-3mol·kg-1concentration of Triton X-100 and all concentrations of the drug.But for 2.0 × 210-3mol·kg-1of Triton X-100 the Δvalue was obtained to be positive at the lower concentration of drug only and at higher concentration of drug its value changes into negative.In the presence of salts,the free energy of transfer(Δ)values of the TX-100-CFT mixed system were achieved to be positive at the only lowest concentration of salts and their values change into negative at higher concentration of salts.The negative value of Δwas further increased with an increase in the concentration of salt.

The enthalpy-entropy compensation,the relationship between Δand Δis linear and the value ofR2in the order of 0.99992-1 was observed in every studied system(Fig.S20(supplementary materials))in accordance with the subsequent regression Eq.(7)[64]

In Eq.(7),the slopeTcis the compensation temperature,illustrates the solvation portion of aggregation phenomena as well as helps as the base of evaluation for contrary patterns of compensation conduct and the intercept Δwas the intrinsic enthalpy gain.For all systems in aqueous solution as well as in the attendance of CFT/(CFT+salts),the values of Δand Tcare shown in Table S10(supplementary materials).The values of Tclying in the range 310.67-340.31 K have been employed as an indicative test for the alliance of H2O in the solution of the protein[65].The Δvalues are positive and the positive values of TX-100 solutions tend to decrease due to the addition of solutes which is the indicative of the increase in stability of the system.

4.Conclusions

In the present study,the phase separation phenomenon of the nonionic surfactant,TX-100 solution has been estimated in aqueous and in the attendance of drug/(drug+salts).The variation of CP values of TX-100 by means of the addition of drug CFT or(CFT+salts)indicates that a considerable amount of aqueous solutions of salts and water soluble drug created a good interaction with TX-100 molecules.The addition of salts lowers the CP of(TX-100+CFT)and the reduction of CP values was in the following order:NaCO3＞Na2SO4＞NaCl;K2SO4＞KCO3＞KCl and(NH4)2SO4＞Na2CO3＞NH4Cl.The cation efficiency in reducing the CP is found to follow the order:Na+＞K+＞.The enthalpy(ΔHc)and entropyvalues are obtained to be negative that point out the occurrence of exothermic interactions for the duration of phase separation.The values of Δwere obtained to be positive in all the systems indicating that the clouding processes were nonspontaneous in nature.The Δvalues were found to be positive and their values reduce due to the addition of solutes which is indicative of the enhanced stability of the system.

Acknowledgments

Prof.Dr.Md.Anamul Hoque would like to acknowledge Jahangirnagar University,Savar,Dhaka,Bangladesh for providing financial support to carry out the research work.

Supplementary Material

Tables and Figures are available free of charge as Supplementary Information(SI)for this article at www.sciencedirect.com.Supplementary data associated with this article can be found in the online version,at https://doi.org/10.1016/j.cjche.2017.10.011.

[1]S.Schreier,S.V.Malheiros,E.de Paula,Surface active drugs:Self-association and interaction with membranes and surfactants.Physicochemical and biological aspects,Biochim.Biophys.Acta1508(2000)210-234.

[2]M.J.Rosen,Surfactants and Interfacial Phenomena,third ed.Wiley,New York,2004.

[3]N.Azum,M.A.Rub,A.M.Asiri,Micellization and interfacial behavior of the sodium salt of ibuprofen-BRIJ-58 in aqueous/brine solutions,J.Solut.Chem.45(2016)791-803.

[4]M.A.Rub,N.Azum,A.M.Asiri,Interaction of cationic amphiphilic drug nortriptyline hydrochloride with TX-100 in aqueous and urea solutions and the studies of physicochemical parameters of the mixed micelles,J.Mol.Liq.218(2016)595-603.

[5]D.Kumar,M.A.Rub,Effect of sodium taurocholate on aggregation behavior of amphiphilic drug solution,Tenside Surf.Deterg.52(2015)464-472.

[6]M.A.Rub,N.Azum,A.M.Asiri,Binary Mixtures of Sodium Salt of Ibuprofen and Selected Bile Salts:Interface,Micellar,Thermodynamic,and Spectroscopic Study,J.Chem.Eng.Data62(2017)3216-3228.

[7]D.Kumar,M.A.Rub,Kinetic study of nickel-glycylglycine with ninhydrin in alkanediylα,ω-gemini(m-s-m type)surfactant system,J.Mol.Liq.240(2017)253-257.

[8]H.Siddiqui,M.Kamil,M.Panda,Kabir-ud-Din,Solubilization of phenanthrene and fluorene in equimolar binary mixtures of gemini/conventional surfactants,Chin.J.Chem.Eng.22(2014)1009-1015.

[9]M.A.Rub,F.Khan,M.S.Sheikh,N.Azum,A.M.Asiri,Tensiometric, fluorescence and 1H NMR study of mixed micellization of non-steroidal anti-inflammatory drug sodium salt of ibuprofen in the presence of non-ionic surfactant in aqueous/urea solutions,J.Chem.Thermodyn.96(2016)196-207.

[10]D.Bhatt,K.C.Maheria,J.Parikh,Studies on surfactant-ionic liquid interaction on clouding behavior and evaluation of thermodynamic parameters,J.Surfactant Deterg.16(2013)547-557.

[11]D.Kumar,K.-E.Neo,M.A.Rub,Dipeptide glycyl-glycine(Gly-Gly)-ninhydrin reaction:Effect of alkanediyl α,ɷ-bis(dimethylcetylammonium bromide)(16-s-16,s=4,5,6)gemini surfactants on the reaction rate,Tenside Surf.Deterg.53(2016)168-175.

[12]M.A.Hoque,M.M.Alam,M.R.Molla,S.Rana,M.A.Rub,M.A.Halim,M.A.Khan,F.Akhtar,Interaction of cetyltrimethylammonium bromide with drug in aqueous/electrolyte solution:A combined conductometric and molecular dynamics method study,Chinese J.Chem.Eng.(2017),https://doi.org/10.1016/j.cjche.2017.06.016.

[13]D.Myers,Surfactant Science and Technology,second ed.VCH,New York,1992.

[14]S.A.Buckingham,C.J.Garvey,G.G.Warr,Effect of head-group size on micellization and phase behavior in quaternary ammonium surfactant systems,J.Phys.Chem.97(1993)10236-10244.

[15]T.Inoue,T.Misono,Cloud point phenomena for POE-type nonionic surfactants in imidazolium-based ionic liquids:Effect of anion species of ionic liquids on the cloud point,J.Colloid Interface Sci.337(2009)247-253.

[16]H.Arai,M.Murata,K.Shinoda,Interaction between polar and surfactant.Composition of the complex between poly(vinylpyrrolidinone)and sodium alkyl sulfate as revealed by surface tension,dialysis,and solubilization,J.Colloid Interface Sci.37(1971)223-227.

[17]S.Chauhan,K.Sharma,K.Kumar,G.Kumar,A comparative study of micellization behavior of an ethoxylated alkylphenol in aqueous solutions of glycine and leucine,J.Surfactant Deterg.17(2014)161-168.

[18]C.Batigöc,H.Akbas,Spectrophotometric determination of cloud point of Brij 35 nonionic surfactant,Fluid Phase Equilib.303(2011)91-95.

[19]H.Schott,Effect of inorganic additives on solutions of nonionic surfactants—XVI.Limiting cloud points of highly polyoxyethylated surfactants,Colloids Surf.A Physicochem.Eng.Asp.186(2001)129-136.

[20]Z.Huang,T.Gu,The effect of mixed cationic-anionic surfactants on the cloud point of non-ionic surfactant,J.Colloid Interface Sci.138(1990)580-582.

[21]R.K.Mahajan,J.Chawla,M.S.Bakshi,Depression of the cloud point of Tween in presence of glycol additives and triblock polymers,Colloid Polym.Sci.282(2004)1165-1168.

[22]M.B.Khan,M.A.Hoque,D.M.S.Islam,Physicochemical investigation of the clouding behavior and thermodynamics ofp-tert-alkylphenoxy poly(oxyethylene)ether micelles in aqueous environment and in the presence of dios,J.Chem.Thermodyn.89(2015)177-182.

[23]A.D.Mudawadkar,G.H.Sonawane,T.J.Patil,Thermodynamics of micellization of nonionic surfactant Triton X-100 in presence of additive Poly-N-vinyl-pyrrolidone using clouding phenomenon,Orient.J.Chem.29(1)(2013)227-233.

[24]K.Shinoda,T.Makagawa,B.Tanamushi,T.Ishemushi,Colloidal Surfactants,Academic Press,New York,1963.

[25]M.Alauddin,T.Parvin,T.Begum,Effect of organic additives on the cloud point of Triton X-100 micelles,J.Appl.Sci.9(12)(2009)2301-2306.

[26]R.K.Mahajan,K.K.Vohra,N.Kaur,V.K.Aswal,Organic additives and electrolytes as cloud point modifiers in octylphenol ethoxylate solutions,J.Surfactant Deterg.11(2008)243-250.

[27]K.S.Sharma,S.R.Patil,A.K.Rakshit,Study of the cloud point of C12Ennonionic surfactants:Effect of additives,Colloids Surf.A219(2003)67-74.

[28]K.Panchal,A.Desai,T.Nagar,Physicochemical behavior of mixed nonionic-ionic surfactants in water and aqueous salt solutions,J.Dispers.Sci.Technol.27(2006)33-38.

[29]M.A.Hoque,A.Mitu,M.O.F.Patory,D.M.S.Islam,Physicochemical studies of effect of additives on clouding behavior and thermodynamics of polyoxyethylene(20)sorbitan monooleate,Indian J.Chem.55A(2016)793-802.

[30]D.K.Rout,S.Chauhan,A.Agarwal,Cloud point and microemulsion phase behavior of sodium linear alkylbenzene sulfonate with tetrabutyl-and benzyltributylsubstituted ammonium halides,Ind.Eng.Chem.Res.48(2009)8842-8847.

[31]T.Inoue,H.Ohmura,D.Muratr,Cloud point temperature of polyoxyethylenetype nonionic surfactants and their mixtures,J.Colloid Interface Sci.258(2003)374-382.

[32]R.N.Brogden,A.Ward,Ceftriaxone.A reappraisal of its antibacterial activity and pharmacokinetic properties,and an update on its therapeutic use with particular reference to once-daily administration,Drugs35(1988)604-645.

[33]J.S.Joyal,N.Sitaras,F.Binet,J.C.Rivera,A.Stahl,K.Zaniolo,Z.Shao,A.Polosa,T.Zhu,D.Hamel,M.Djavari,D.Kunik,J.C.Honoré,E.Picard,A.Zabeida,D.R.Varma,G.Hickson,J.Mancini,M.Klagsbrun,S.Costantino,C.Beauséjour,P.Lachapelle,L.E.H.Smith,S.Chemtob,P.Sapieha,Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A,Blood117(2011)6024-6035.

[34]C.J.Pendegrass,D.Gordon,C.A.Middleton,S.N.M.Sun,G.W.Blunn,Sealing the skin barrier around transcutaneous implants:In vitro study of keratinocyte proliferation and adhesion in response to surface modifications of titanium alloy,J.Bone Joint Surg.90(2008)114-121.

[35]M.A.Ferguson,N.L.Alderson,S.G.Trost,D.A.Essig,J.R.Burke,J.L.Durstine,Effects of four different single exercise sessions on lipids,lipoproteins,and lipoprotein lipase,J.Appl.Physiol.85(1998)1169-1174.

[36]N.Azum,M.A.Rub,A.M.Asiri,W.A.Bawazeer,Micellar and interfacial properties of amphiphilic drug-non-ionic surfactants mixed systems:Surface tension, fluorescence and UV-vis studies,Colloids Surf.A522(2017)183-192.

[37]J.L.Li,D.S.Bai,B.H.Chen,Effects of additives on the cloud points of selected nonionic linear ethoxylated alcohol surfactants,Colloids Surf.A Physicochem.Eng.Asp.346(2009)237-243.

[38]P.Parekh,R.U.Yerramilli,P.Bahadur,Cloud point and thermodynamic parameters of a non-ionic surfactant heptaoxyethylene dodecyl ether(C12E7)in presence of various organic and inorganic additives,Indian J.Chem.A52(2013)1284-1290.

[39]T.Gu,P.A.Galera-Gomez,The effect of different alcohols and other polar organic additives on the cloud point of Triton X-100 in water,Colloids Surf.A Physicochem.Eng.Asp.147(1999)365-370.

[40]D.Blankschtein,G.M.Thurston,G.B.Benedek,Phenomenological theory of equilibrium thermodynamic properties and phase separation of micellar solutions,J.Chem.Phys.85(1986)7268-7288.

[41]R.C.da Silva,W.Loh,Effect of additives on the cloud points of aqueous solutions of ethylene oxide-propylene oxide-ethylene oxide block copolymers,J.Colloid Interface Sci.202(1998)385-390.

[42]K.Shinoda,H.Takeda,The effect of added salts in water on the hydrophile-lipophile balance of nonionic surfactants:The effect of added salts on the phase inversion temperature of emulsions,J.Colloid Interface Sci.32(1970)642-646.

[43]R.Heusch,Structures in surfactant/water mixtures and their use in biotechnology,BTF-Biotech Forum3(1986)1-8.

[44]J.Parikh,J.Rathore,D.Bhatt,M.Desai,Clouding behavior and thermodynamic study of nonionic surfactants in presence of additives,J.Dispers.Sci.Technol.34(2013)1392-1398.

[45]M.El Nakaly,L.D.Ford,S.E.Friberg,D.W.Larsen,The structure of lamellar lyotropic liquid crystals from lecithin and alkanediols,J.Colloid Interface Sci.84(1981)228-234.

[46]M.S.Alam,Kabir-ud-Din,A.B.Mandal,Evaluation of thermodynamic parameters of some amphiphilic drugs in presence of sugars at the cloud point,Colloids Surf.B105(2013)236-245.

[47]C.K.Bahal,H.B.Kostenbauder,Interaction of preservatives with macromolecules V binding of chlorobutanol,benzyl alcohol,and phenylethyl alcohol by nonionic agents,J.Pharm.Sci.53(1964)1027-1029.

[48]J.M.Hierrezuelo,J.A.Molina-Bolívar,C.C.Ruiz,An energetic analysis of the phase separation in non-ionic surfactant mixtures:The role of the headgroup structure,Entropy16(2014)4375-4391.

[49]M.A.Rub,A.M.Asiri,A.Khan,A.A.P.Khan,N.Azum,S.B.Khan,Kabir-ud-Din,Investigation of micellar and phase separation phenomenon of the amphiphilic drug amitriptyline hydrochloride with cationic hydrotropes,J.Solut.Chem.42(2013)390-411.

[50]N.Azum,M.A.Rub,A.M.Asiri,Energetics of clouding phenomenon in amphiphilic drug imipramine hydrochloride with pharmaceutical excipients,Pharm.Chem.J.48(2014)201-208.

[51]A.Z.Naqvi,M.A.Rub,Kabir-ud-Din,Study of phospholipid-induced phase-separation in amphiphilic drugs,Colloid J.77(2015)525-531.

[52]Kabir-ud-Din,M.A.Rub,M.S.Sheikh,Cloud point modulation of an amphiphilic drug with pharmaceutical excipients,J.Chem.Eng.Data55(2010)5642-5652.

[53]D.C.Robins,I.L.Thomas,The effect of counterions on micellar properties of 2-dodecylaminoethanol salts:I.Surface tension and electrical conductance studies,J.Colloid Interface Sci.26(1968)407-414.

[54]M.A.Hoque,M.A.Khan,M.D.Hossain,Interaction of cefalexin monohydrate with cetyldimethylethylammonium bromide,J.Chem.Thermodyn.60(2013)71-75.

[55]Kabir-ud-Din,S.Khatoon,A.Z.Naqvi,Nonelectrolyte-induced CP variation of TX-114+TBAB system,Acta Phys.-Chim.Sin.24(2008)1180-1184.

[56]J.H.Clint,Surfactant Aggregation,Chapman and Hall,New York,1992.

[57]G.C.Kresheck,in:F.Franks(Ed.),Water.A Comprehensive Treatise,Plenum,New York,1995.

[58]D.Kumar,M.A.Rub,Aggregation behavior of amphiphilic drug promazine hydrochloride and sodium dodecylbenzenesulfonate mixtures under the influence of NaCl/urea at various concentration and temperatures,J.Phys.Org.Chem.29(2016)394-405.

[59]M.Rahman,M.A.Khan,M.A.Rub,M.A.Hoque,Effect of temperature and salts on the interaction of cetyltrimethylammonium bromide with ceftriaxone sodium trihydrate drug,J.Mol.Liq.223(2016)716-724.

[60]M.Rahman,M.A.Khan,M.A.Rub,M.A.Hoque,A.M.Asiri,Investigation of the effect of various additives on the clouding behavior and thermodynamics of polyoxyethylene(20)sorbitan monooleate in absence and presence of ceftriaxone sodium trihydrate drug,J.Chem.Eng.Data62(2017)1464-1474.

[61]D.Kumar,M.A.Rub,Effect of anionic surfactant and temperature on micellization behavior of promethazine hydrochloride drug in absence and presence of urea,J.Mol.Liq.238(2017)389-396.

[62]M.R.Molla,M.A.Rub,A.Ahmed,A.Hoque,Interaction between tetradecyltrimethylammonium bromide and benzyldimethylhexadecylammonium chloride in aqueous/urea solution at various temperatures:An experimental and theoretical investigation,J.Mol.Liq.238(2017)62-70.

[63]S.K.Shivaji,A.K.Rakshit,Investigation of the properties decaoxyethylene n-dodecyl ether,C12E10,in the aqueous sugar-rich region,J.Surf.Deterg.7(2004)305-316.

[64]L.J.Chen,S.Y.Lin,C.C.Huang,Effect of hydrophobic chain length of surfactants on enthalpy-entropy compensation of micellization,J.Phys.Chem.102(1998)4350-4356.

[65]R.Lumry,S.Rajender,Enthalpy-entropy compensation phenomena in water solutions of proteins and small molecules:A ubiquitous property of water,Biopolymers9(1970)1125-1127.