Phase Separation of Amphiphilic Drug Amitriptyline Hydrochloride in

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

Phase Separation of Amphiphilic Drug Amitriptyline Hydrochloride in the Presence of Additives: Role of Ethanol Jackson Gurung and Ajmal Koya Pulikkal* Department of Chemistry, National Institute of Technology Mizoram, Chaltlang, Aizawl 796012, India

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S Supporting Information *

ABSTRACT: In this work, the effect of ethanol (EtOH) at different weight percentages (wt %) (0, 5, 10, and 15% w/w) is accounted for in the clouding phenomena of the AMT drug with/without additives (inorganic salts and conventional and gemini surfactants). The critical micelle concentration (cmc) and degree of counterions dissociation (α) of AMT solution at 30 °C in SP buffer (pH 6.7), studied through conductometric studies, are found to be enhanced with the increase in ethanol content due to the reduction in the dielectric constant of mixed media. A dye solubilization study performed under identical physicochemical conditions exhibited supporting results. Clouding could not be observed in 20 wt % EtOH−WR mixed media at pH 6.7. The effects of additives on the CP in 15 wt % EtOH−WR at a pH of 6.95 were also studied. Furthermore, the effect of pH (range 6.7 to 7.15) on the CP in the presence of KCl at the same composition of the mixed media reduce the clouding temperature due to the deprotonation of AMT headgroups. For up to 10 wt % EtOH−WR mixed media, the effect of anionic and cationic co-ions on the CP is found to follow the order Br− > Cl− > F− and NH4+ > Li+ > Na+ > K+, respectively. When surfactants were used as additives, the hydrophobicity was found to be responsible for higher CP values and follow the order TTAB < CTAB < 14-m-14, where m is the length of the spacer. reaching their final target.7 The applications of such drugs may, sometime, act unusually and cause several undesirable effects, for example, anticholinergic, cardiovascular, antiarrhythmic, etc.,8 therefore requiring a proper channel to target it in the right zone at an appropriate time, minimizing the side effects without compromising the drug’s efficacy.9 Amitriptyline hydrochloride (AMT) is an amphiphilic drug and is used as an antidepressant for the treatment of major depressive disorder and other conditions.8 Hydrophobic and hydrophilic portions of AMT are a tricyclic ring and a tertiary amine group, respectively. The solubility of standard AMT hydrochloride in water is greater than 500 mg/mL.10 The temperature at which micellar solution of a particular concentration becomes cloudy due to phase separation is known as the cloud point (CP). The clouding of such system is a reversible process, and the phenomenon occurs due to the subtle balance in the interactions between hydrophobic and hydrophilic groups.11 During clouding, the physical change of phase separation from the aqueous phase as a result of the weakening of hydrogen bonds between the amphiphile and water molecules occurs, resulting in the formation of dilute surfactant and coacervate phases.2,12,13 The CP is considered to be a critical parameter in several applications such as

1. INTRODUCTION Amphiphilic molecules consist of hydrophobic tails and hydrophilic headgroups. They self-assemble to form welldefined aggregates by way of hydrophobic interaction within the nonpolar hydrocarbon part, and the electrostatic interaction of the polar or ionic headgroups and the aggregates thereby formed are called micelles.1,2 The self-assembly in these associated colloids is a natural and spontaneous process which comes into play as a result of noncovalent interactions such as van der Waals, electrostatic, hydrogen bonding, and hydrophilic/hydrophobic interactions.3 The self-association of amphiphilic drugs depends on their molecular structure and hydrophilic−lipophilic balance (HLB), and it can be controlled by the drug concentration and physicochemical condition such as pH, temperature, and the presence of additives.4,5 The resultant structure formed by these drugs, particularly that associated with anesthetics, tranquilizers, antidepressants, and antibiotic activity, with biological membranes can be considered to be a complex form of amphiphilic bilayers. Furthermore, the interaction of the drugs with cell membranes largely depends on the presence of foreign substances and also drug−additive interactions. For this reason, complete understanding of the course of the interaction of a drug with foreign substances is desirable before the application of the drug in the human body.6 It has been found that amphiphilic drugs are solubilized in body fluids and that they interact with membranes of the organism before © XXXX American Chemical Society

Received: June 5, 2018 Accepted: August 17, 2018

A

DOI: 10.1021/acs.jced.8b00463 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Chemical Sample Table sample no.

chemical name

CAS registry number

source

fraction purity

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

amitriptyline hydrochloride (AMT) hexadecyltrimethylammonium bromide (CTAB) tetradecyltrimethylammonium bromide (TTAB) Sudan III dye lithium chloride anhydrous (LiCl) ethanol absolute (EtOH) potassium chloride (KCl) potassium fluoride anhydrous (KF) potassium bromide (KBr) sodium chloride (NaCl) ammonium chloride (NH4Cl) sodium dihydrogen phosphate monohydrate (NaH2PO4·H2O) trisodium phosphate dodecahydrate (Na3PO4·12H2O)

549-18-8 57-09-0 1119-97-7 85-86-9 7447-41-8 64-17-5 7447-40-7 7789-23-3 7758-02-3 7647-14-5 12125-02-9 10049-21-5 10101-89-0

Sigma Sigma Sigma Sigma Alfa Aesar Emsure, Merck SDFCL Fisher Scientific SDFCL SDFCL SDFCL Himedia Himedia

≥98% ≥99% ≥99% technical grade ≥99% ≥99.5% ≥97% ≥99.5% ≥99.9% ≥99% ≥98% ≥97%

10 mm (mmol kg−1) SP buffer.1,25 The pH of the solutions was checked by pH 2700 meter (Eutech Instruments, Singapore). 2.2. Methods. 2.2.1. Conductance Measurements. Conductance measurements of the AMT drug solution in pure water as well as in mixed media at a pH of 6.7 and at 30 °C were performed on a CON 2700 conductivity meter (Eutech Instruments, Singapore) having a cell constant of 0.527 cm−1. The temperature of the system under investigation was kept constant by placing the cell in a temperaturecontrolled water bath. 2.2.2. Dye Solubilization Measurement. The effects of ethanol on self-aggregation of the AMT drug was studied through dye (Sudan III) solubilization measurements. Drug solutions (70 mmol kg−1) were prepared in pure water and in 5, 10, 12.5, 15, 17.5, and 20 wt % EtOH−WR mixed media without additives. The dye (10 mg) was mixed with 8 g of these drug solutions by vigorously stirring at 1000 rpm for about 10 min, and these solutions were filtered using a 0.45 μm syringe filter (Millipore Milliex-HV). After 24 h, the spectra were recorded in the range of 400−600 nm using a Shimadzu UV-1800 UV−visible spectrophotometer at 30 °C connected to a temperature-adjustment facility (TCC-100, Shimadzu). 2.2.3. Cloud-Point (CP) Measurements. The clouding of fixed [AMT] solutions was examined according to the method reported by Albertsson and modified by Blankschtein et al.26,27 based on the visual observation of phase separation. The CP values of the drug in 0, 5, 10, and 15 wt % EtOH−WR mixed media, in the absence and presence of additives, were evaluated by placing Pyrex glass tubes containing drug solutions into a temperature-controlled water bath. The temperature of the water bath was slowly increased at a rate of 0.1 °C/min until the drug solution became turbid (became cloudy), and this particular temperature was noted as CP. Experiments were repeated at least three times for each system, and the uncertainty in the measurement of CP was found to be ±1%. The structure of amphiphilic drug AMT is provided in Scheme 1.

wetting, cleaning, and foaming,14 and this technique is utilized in surfactant-based extraction processes of organic compounds and proteins.15 The worth of the clouding system lies in the fact that it generates a safe environment for the extraction of cells or protein where it will not be damaged and can be used as a new nonaqueous medium for the biocatalysis and biotransformation processes. Moreover, these systems are easy to manipulate, reliable to scale up, and simple and effective to operate.13 Solvents such as alcohol and their ethers with ethylene glycol and glycerol find applications in areas such as detergents, pharmaceuticals, cosmetics, coatings, paints, and inks. Alcohols and glycerol are also known to alter the micellar behavior of surfactants.16,17 The cloud point of amphiphilic drugs can significantly vary in the presence of additives and with pH. Human blood plasma normally has a pH of 7.4. A failure in the pH-regulating mechanism can lead to uncontrolled diabetes (because of acidosis), and irreparable damage or even death may occur if the pH of the blood falls below 6.8.18 Recently, we have reported the effect of ethylene glycol and glycerol on the CP of the AMT drug in the presence of conventional and gemini surfactants.19 In continuation, the motive of the present study is to determine the effects of salt and surfactants on the CP of AMT in different concentrations (wt %) of ethanol− water (EtOH−WR) mixed media. Although several works have been reported in the literature on the CP of AMT with or without additives in aqueous media,7,20−23 to the best of our knowledge no papers focus on the effect of EtOH by varying the composition of mixed media with or without additives. Therefore, it is vital to have knowledge of the interaction fashion of amphiphilic drugs with EtOH−WR mixed media and the role of additives in such systems from fundamental and application points of view.

2. MATERIALS AND METHODS 2.1. Materials. Details of the chemicals used in the present work are given in Table 1. Gemini surfactants tetramethylene1,4-bis(tetradecyldimethylammonium bromide) (14-4-14), pentamethylene-1,5-bis(tetradecyldimethylammonium bromide) (14-5-14), and hexamethylene-1,6-bis(tetradecyldimethylammonium bromide) (14-6-14) were synthesized following the procedure reported in the literature.24 All solutions were prepared by using doubly distilled deionized water (specific conductivity 1−2 μS cm−1 at room temperature). Sodium dihydrogen phosphate monohydrate and trisodium phosphate dodecahydrate were used to prepare

3. RESULTS AND DISCUSSION 3.1. Effect of EtOH on the Critical Micelle Concentration (cmc). 3.1.1. Conductometric Study. The intersection points in the plot of specific conductance (κ) against the molal concentration of drug solution was taken as minimum concentration required for micelle formation (critical micelle concentration, cmc).28 B



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Scheme 1. Ball-and-Stick Model of Amitriptyline Hydrochloride (AMT)

Table 2. Critical Micelle Concentration (cmc) and Degree of Counterion Dissociation (α) Values of AMT in Water and in Different Concentrations (wt %) of EtOH−WR Mixed Media at 30 °C along with the CP of a 50 mmol kg−1 AMT Solution at pH 6.7a wt % of EtOH−WR (w/w)

cmc (mmol kg−1)

α

CP (°C)

0 5 10 15 20

42.64 45.40 50.15 53.24 58.02

0.57 0.64 0.67 0.68 0.71

25.2 27.6 28.6 68.6

The uncertainties in cmc, α, and CP are within ±2, ±3, and ±1%, respectively.

a

premicellar and postmicellar concentration ranges. The decrease in κ of the drug solution with the addition of EtOH could be due to the formation of a solvated layer over the drug micellar surfaces, lowering the mobility of the drug molecules. It is well known that the mixing of cosolvents alters the bulk properties of water due to their interaction with the added cosolvents. Figure 1b shows the rise in cmc and degree of counterion dissociation (discussed in section 3.2) values of AMT with the incorporation of EtOH. The results show an enhancement in the cmc with the increase in wt % of EtOH in the mixed media. The dielectric constant of EtOH (εEtOH = 25.3) is much less than that of pure water (εWR = 80.1) at 293.2 K.30 The crucial adjustment in the cmc is due to the mixing of EtOH with pure water through an indirect, solventmediated mechanism which lowers the ε of the mixed media enhancing the electrostatic interactions.31 As a result, the repulsion between the micellar headgroups of the drug molecule increases and a greater drug concentration would be required to form the micelles.

Plots of specific conductance against the concentration of AMT in pure water and in EtOH−WR mixed media ranging from 0 to 20 wt % (with an increment of 5 wt %) at pH 6.7 and at 30 °C are shown in Figure 1a. The obtained cmc values are given in Table 2. The cmc of AMT in pure water is found to be 42.64 mmol kg−1. AMT molecules form cationic micelles at pH 6.7 wherein the tertiary nitrogen moiety becomes positively charged due to the protonation under acidic conditions.20,29 It can be seen from Figure 1a that the specific conductance (κ) decreases with the increase in wt % of EtOH in both the

Figure 1. (a) Plots of specific conductivity (κ) vs [AMT] in various compositions of EtOH−WR mixed media at 30 °C, pH 6.7. (b) Variation of cmc and α values of AMT with the compositions of EtOH−WR mixed media at 30 °C, pH 6.7. C



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3.1.2. Dye Solubilization Study. In general, amphiphilic drug molecules find application in contemporary pharmaceutical biotechnology due to the solubilization of insoluble material either in aqueous or in organic systems. We used the Sudan III dye as a probe for the qualitative analysis of aggregate formation of the AMT drug in different concentrations (wt %) of EtOH−WR mixed media. The absorbance of Sudan III dye solubilized in 70 mmol kg−1 AMT drug solutions in pure water and in different compositions of EtOH−WR mixed media (i.e., 5, 10, 12.5, 15, 17.5, and 20 wt %) was measured on a UV−visible spectrophotometer. The spectra obtained in such solutions at a pH of 6.7 and at 30 °C are shown in Figure 2. Although the concentrations of AMT

and Sudan III dye were same in all compositions of EtOH− WR mixed media, the λmax values were found to be declined with the increase in wt % of EtOH. This implies that the aggregates formed by the drug may not be effective at solubilizing the given amount of dye when the EtOH content is increased. The inclusion of EtOH with pure water lowers the permittivity of the resultant mixed media, enhancing the repulsive interactions among cationic headgroups of drug molecules. Furthermore, the same shall be responsible for increasing the cmc values for ionic amphiphiles. However, as the concentration of drug is fixed in all compositions, then the formation of loose micelles can be expected wherein the solubilization of the dye becomes difficult and, as a result, the absorbance values decrease. The results of absorbance spectra measured in the wavelength range of 400−600 nm in pure water and in different compositions of the EtOH−WR mixed media indicate that the relative magnitude of the cmc increases with the inclusion of EtOH. 3.2. Effect of EtOH on the Degree of Counterion Dissociation (α). The degree of counterion dissociation (α) of AMT solutions was determined from the ratios of postmicellar slopes (s2) to premicellar slopes (s1) in the conductivity vs molal concentration of AMT.28 The obtained α values are given in Table 2. Chloride ions are the counterions associated with AMT drug molecule and a particular fraction of which is bound over the headgroups of AMT in the stern layer to stabilize the micelles. It can be seen that, on varying the compositions of the mixed media, the extent of dissociation of the counterions gradually increases. The increase in the repulsive interactions among the headgroups of the AMT molecule with an increase in the wt % of EtOH can enlarge the surface area per headgroup. As a result, a weaker interaction between the counterions and headgroups of AMT is expected due to the penetration of EtOH into palisade layers of the micelles, reducing the binding probability of the counterions or increasing the α values as can be seen from Figure 1b and Table 2.

Figure 2. Spectra of Sudan III dye with a 70 mmol kg−1 AMT drug solution in pure water and in different concentrations (wt %) of EtOH−WR mixed media at 30 °C, pH 6.7.

Figure 3. Effects of anionic co-ions on the CP of 50 mmol kg−1 AMT in different compositions of EtOH−WR mixed media. The vertical line, |, represents precipitate formation. D



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Figure 4. Effect of cationic co-ions on the CP of 50 mmol kg−1 AMT solution in different compositions of EtOH−WR mixed media.

3.3. Cloud Point (CP) of AMT in the Presence of Additives. 3.3.1. Effect of Inorganic Salts. A great deal of research has been conducted on CP determination by visual methods in the past decade.2,6,7,26,27,32 Recent work on the clouding phenomenon and other related parameters of drugs ceftriaxone sodium trihydrate and the phenothiazine family reported in the literature have also used the same method for CP determination.33−35 It is known that the clouding behavior of drugs depends on the solvation or desolvation equilibrium existence. The presence of additives in water and in EtOH− WR mixed media can change such an equilibrium, and as a result, the CP of the drug solutions may vary significantly. In this work, a 50 mmol kg−1 AMT drug concentration was used in CP measurements to facilitate the interaction of additives with the drug micellar solution. The extent of interaction and binding of counterions with the surfactant micelles is significantly influenced by the nature of the counterions.36,37 The variation of the CP of AMT with the addition of three inorganic salts (KF, KCl, and KBr) in water and in different compositions of EtOH−WR mixed media, as illustrated in Figure 3, shows the effect of anions. The effect of these co-ions on the CP of AMT in water and 5 and 10 wt % EtOH−WR mixed media at pH 6.7 follows the order Br− > Cl− > F−. At 15% EtOH−WR mixed media, the observed CP was 68.6 °C at pH 6.7 (which is close to the boiling point of EtOH, bp = 78 °C), and it may not be appropriate to see the effect of additives in such systems because they may cross the bp easily. Therefore, CP was checked at a higher pH of 6.95 in which the temperature of clouding was found to be 42.2 °C and the effect of additives was studied at this pH. The clouding of the drug solution can be explained by the hydration/solvation of anionic co-ions and their electrostatic interaction with the drug micellar system. According to the Hofmeister series, F− ions with a small size and a high charge density, categorized as kosmotropes, facilitate more hydration and are known to be a water-making structure whereas Cl− and Br− ions with larger sizes, small

charge densities, and high polarizabilities known as chaotropes are considered to be water-breaking structures in aqueous systems. The efficiency of such co-ions to impact the micellization is accounted for by their ability to interact with the micellar aggregates. The hydrated radii of fluoride and bromide anions are 3.52 and 3.30 Å, respectively, in aqueous solution.38 The effect of co-ions on the CP of AMT at pH 6.7 up to 10 wt % EtOH−WR mixed media follows the order Br− > Cl− > F−. Strong binding of Br− ions with positively charged AMT micelles can effectively decrease the electrostatic repulsion between the micellar headgroups facilitating the growth of micelles. Consequently, CP can be higher for Br− than for Cl−/F− anions in which the binding with the micelles can be considered to be relatively weak. It is pertinent to mention here that CP measurements of the AMT drug (50 mmol kg−1) in pure WR and in EtOH−WR mixed media could not be carried out beyond 150 mmol kg−1 KBr due to precipitation. The precipitation could be due to the formation of nonmicellar systems of drug solution in the aqueous system as well as in EtOH−WR mixed media. In the presence of F− ions, the CP gradually increases when the concentration of KF salt is varied between 200 and 300 mmol kg−1 in WR and 5 and 10 wt % EtOH−WR mixed media after which the values remained almost constant. For KCl and KBr, CP increases sharply over the studied concentration range. The ability of amphiphilic molecules to separate from one phase to another depends on the net charge of the molecule and the ionic strength of the solution. The successive change in the dielectric constant (ε) of the resultant mixed media upon inclusion of EtOH can affect the electrostatic interaction in the solution.39 The CP values were slightly higher for all three salts (KF, KCl, and KBr) in 10 wt % EtOH−WR than in 5 wt % EtOH−WR mixed media and pure water at pH 6.7. The hydrated/solvated sizes of co-ions decrease with increasing wt % of EtOH in mixed media due to the diminution in the polarity of the bulk phase. The extent of ion association or dissociation after adding electrolytes usually depends on the E



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Figure 5. Effect of EtOH−WR composition on the CP of AMT in the presence of salts.

mixed media, it can be seen that clouding behavior is different in 15 wt % EtOH−WR mixed media, which was studied at a slightly higher pH of 6.95. In this case, no clouding was found after 26 mmol kg−1 NH4+. The variation CP of AMT solutions in different concentrations (wt %) of EtOH−WR mixed media in the presence of each studied salt is depicted in Figure 5. 3.3.2. Effect of pH on the CP in 15 wt % EtOH−WR Mixed Media in the Presence and Absence of KCl. The effect of pH on the clouding of drugs in an aqueous medium has been reported in earlier studies.25,38,41,42 An increase in CP is observed with the increase in the concentration (wt %) of EtOH due to augmented repulsive interactions between AMT headgroups. The effect of pH on the CP of AMT (with or without KCl salt) in 15 wt % EtOH−WR composition can be seen from the plots shown in Figure 6a,b. The CP of AMT solution in the studied composition of the mixed media increases with the reduction in the pH (7.15 to 6.7). The protonation of nitrogen in the hydrophilic portion depends on the pH of the solution. As the pH rises from 6.7 to 7.15, the nitrogen can be deprotonated, reducing both intra- and intermicellar repulsions which in turn diminish the CP. 3.3.3. Clouding of AMT in the Presence of Cationic Conventional/Gemini Surfactants. The effect of conventional surfactants such as TTAB, CTAB, and 14-m-14 gemini surfactants (where m is a polymethylene chain, −(CH2)m−; m = 4, 5, and 6] on CP of the AMT drug solution in different concentrations (wt %) of EtOH−WR media is illustrated in Figure 7. Mixed micelle formation between amphiphilic drugs and cationic surfactants has been reported by several authors,43−49 and the addition of surfactants is known to change the micellar structure of the drug. Their existence as a monomer or micellar form depends on the type of interaction between the two entities. In the case of conventional surfactants, the effect on CP of AMT was found to be directly related to the length of the alkyl chain of surfactants (tail of

properties of solvent or mixed media, which is often decided by the dielectric constant of the mixed media. In 15 wt % EtOH− WR mixed media (at pH 6.95), CP increases up to 148 mmol kg−1 of KF salt, after which it decreases until 588 mmol kg−1. Beyond 588 mmol kg−1, the CP values are found to become stagnant with further increases in concentration. At pH 6.95, the CP is higher for Cl− than for Br− and follows the trend Cl− > Br− > F−. The results show that at 15% EtOH−WR mixed media, the effect of anionic co-ions on the CP of the AMT drug solution does not relate to the Hofmeister series, unlike other studied compositions of EtOH−WR mixed media. The effects of cationic co-ions on the CP of the AMT drug solution in aqueous and in different concentrations (wt %) of EtOH−WR mixed media are illustrated in Figure 4. The variation of CP by these co-ions can be explained according to their ability with respect to hydration, which directly depends on their ionic size and follows the order Li+ < Na+ < K+ < NH4+. The smaller the size, the greater the hydration of such cations and the greater the thermal energy that would be required to remove the water from the AMT drug micelles. Accordingly, most hydrated Li+ ions have higher CP values whereas poorly hydrated K+ ions have smaller CP values in water and in 5 and 10 wt % EtOH−WR mixed media. Alam et al. have also obtained a similar trend for another drug, chlorpromazine hydrochloride, which they studied at 50 mM.40 However, NH4+ shows the least hydration nearly equal to that of the K+ ion but its CP was found to be exceptionally high, and this can be thought of as being due to its hydrogen bonding capability. The effectiveness of cationic co-ions to raise the CP was found be almost equal in the lower concentration region (up to 100 mmol kg−1) in pure water and in 5 wt % EtOH−WR mixed media. The effect of solvent is found to be more prominent from 10 wt % EtOH−WR composition onward. Beyond the 100 mmol kg−1 concentration range, relatively higher CP changes are noticed. On comparing the CP values obtained at lower compositions of F



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found to be distinct with the compositions of the mixed media. The special behavior is believed to be due to the role of a spacer, which imposes an additional geometric restriction on the intramolecular surfactant packing. The shape of micelles progressively becomes more spherical or ellipsoidal with the increase or decrease in the length of the spacer.53 A nonmonotonical increase in the surface charge with the increase in the spacer length has been reported in the literature.52,53 The results suggest that, in case of geminis, polymethylene spacers play a vital role in their clouding behavior. Both the drug and surfactants used herein are cationic in nature, and as a result, micellar repulsion can be associated more with the increase in the concentration of surfactants. This can lead to the formation of large/loose micelles, wherein the hydration/ solvation of headgroups will be greater, leading to higher CP values. The obtained results depict that the CP values are less with the 14-4-14 gemini surfactant than with the other two gemini surfactants in all compositions of EtOH−WR mixed media. For the surfactants used, the capability to augment CP values of AMT is found to follow the order TTAB < CTAB < 14-m-14 (m = 4−6) in the studied compositions of EtOH− WR mixed media. It can be seen that CP values are greater for CTAB than for the 14-4-14 gemini surfactant in the intermediate concentration range in 5 wt % EtOH−WR mixed media, but after 6.95 mmol kg−1 concentration, again CP with a 14-4-14 gemini surfactant increases. Such unique behavior could be due to the peculiar solvent properties as well as the unique nature of gemini at that composition. The variation of the CP of the AMT solution in different concentrations (wt %) of EtOH−WR mixed media in the presence surfactants is plotted in Figure 8. The CP of the AMT drug along with additives are significantly influenced by the addition of EtOH, as can be seen from both Figures 5 and 8 as a result of the change in the solvation of salts/surfactants as well as the micellar system. AMT shows clouding at pH 6.7 up

Figure 6. (a) Effect of pH on the cloud point of 50 mmol kg−1 AMT with KCl salt in 15 wt % EtOH−WR mixed media. (b) Effect of pH on the cloud point of 50 mmol kg−1 AMT without additives in 15 wt % EtOH−WR mixed media.

surfactant): longer-surfactant CTAB shows a higher CP than does TTAB. Compared to conventional surfactants, gemini contains two monomer units of hydrophobic alkyl tails joined by a covalent bond with a polymethylene spacer at the level of their headgroups which offer unique properties such as a relatively low cmc,50 a higher ability to reduce surface tension,50 a greater potential to solubilize water-insoluble compounds, and unusual rheological properties.51,52 The addition of gemini surfactants (14-4-4, 14-5-14, and 14-6-14) boosts the CP values more than does the addition of conventional surfactant (TTAB and CTAB), as clear in Figure 7, and the trend is

Figure 7. Effect of surfactants on the CP of a 50 mmol kg−1 AMT solution in different compositions of EtOH−WR mixed media. G



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Figure 8. Effect of the EtOH−WR composition on the CP of AMT in the presence of surfactants.

to 15 wt % of EtOH in their mixed media with water and it is not observed on heating the system up to bp of EtOH at 20, 25, 30, 35, and 40 wt % compositions of EtOH−WR mixed media. However, in our previous study,19,54 clouding had been observed even up to 40 wt % mixed media under identical physicochemical conditions wherein the solvent was ethylene glycol and glycerol. This can be understood in terms of the difference in their dielectric constant values. EtOH, being the lowest among the three, enhances electrostatic repulsion most between the cationic headgroups of AMT molecules, raising CP values more efficiently even at just 15 wt % composition.

Among anionic co-ions, Br− has higher CP values except for 15% EtOH−WR mixed media, and the binding effect of cationic co-ions follows the order NH4+ > Li+ > Na+ > K+.

4. CONCLUSIONS Experimental results show that the addition of EtOH raises the cmc and CP (with or without additives) values of the AMT solution. The enhancement of the clouding temperature is due to the change in the dielectric constant of the mixed media favoring electrostatic repulsion in the micellar system and changes in the hydrated/solvated sizes of the inorganic ions (when additives are used). In 15 wt % EtOH−WR mixed media, the CP is close to the boiling point of ethanol, and clouding could not be observed in 20 wt % EtOH−WR mixed media at pH 6.7. The conductance studies of AMT solution in the presence of additives reveal that the cmc and degree of counterion dissociation (α) values increase with increasing wt % of EtOH in the mixed media, and the results are supported by the UV−visible spectroscopic study. The decline in clouding temperature with the variation of pH (between 6.7 to 7.15) in 15 wt % EtOH−WR mixed media in the presence of KCl could be due to nonprotonation of the AMT molecules. The hydrophobicity of the surfactants is responsible for boosting the CP, and the efficiency of the studied surfactants is found to follow the order TTAB < CTAB < 14-m-14. Unlike conventional surfactants, gemini surfactants show a distinct CP trend at all concentrations (wt %) of EtOH−WR mixed media.

Corresponding Author

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.8b00463. Cloud points (PDF)

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AUTHOR INFORMATION

*E-mail: [email protected]; [email protected]. ORCID

Ajmal Koya Pulikkal: 0000-0001-9870-6594 Funding

Financial support from the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), New Delhi, India as a research grant (SB/FT/CS146/2013) is highly appreciated. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors are thankful to Prof. Rajat Gupta, Director, NIT Mizoram for providing research facilities. REFERENCES

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