Aggregation and surface phenomena of amitriptyline hydrochloride and cationic benzethonium chloride surfactant mixture in different media

Journal Pre-proof Aggregation and surface phenomena of amitriptyline hydrochloride and cationic benzethonium chloride surfactant mixture in different media

Malik Abdul Rub, Abdulrahman Alabbasi, Naved Azum, Abdullah M. Asiri PII:

S0167-7322(19)35998-7

DOI:

https://doi.org/10.1016/j.molliq.2019.112346

Reference:

MOLLIQ 112346

To appear in:

Journal of Molecular Liquids

Received date:

30 October 2019

Revised date:

10 December 2019

Accepted date:

17 December 2019

Please cite this article as: M.A. Rub, A. Alabbasi, N. Azum, et al., Aggregation and surface phenomena of amitriptyline hydrochloride and cationic benzethonium chloride surfactant mixture in different media, Journal of Molecular Liquids(2019), https://doi.org/10.1016/ j.molliq.2019.112346

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

© 2019 Published by Elsevier.

Journal Pre-proof

Aggregation and surface phenomena of amitriptyline hydrochloride and cationic benzethonium chloride surfactant mixture in different media Malik Abdul Ruba, *, Abdulrahman Alabbasia, Naved Azuma, Abdullah M. Asiria,b a

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

b

of

Arabia Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah-

Jo

ur

na

lP

re

-p

ro

21589, Saudi Arabia

*To whom correspondence should be addressed: Tel.: +966 563671946. E-mail address: [email protected], [email protected]

1

Journal Pre-proof ABSTRACT Mixed association behavior of cationic nature of drug amitriptyline hydrochloride (AMHCl) and surfactant benzethonium chloride (BTC) have been studied at five mole fractions of BTC (1) in current system via surface tension (ST) and fluorescence methods at 298.15 K in occurrence of three dissimilar media (H2O, electrolyte (NaCl), urea (UR)) to evaluate the interactions present amongst them. The evaluated values of critical micelle concentration (cmc) come out beneath the values of cmcid (ideal cmc value) demonstrating attractive interactions amongst the studied constituents (AMHCl and BTC) within mixed micelles. Electrolyte decreases the cmc value of

of

the system while the effect of UR is found to increase in cmc. The micellar mole fraction of BTC

ro

(X1R) analyzed by the Rubingh model in solution mixture, mole fraction at mixed monolayer (X1σ) determined by Rosen model and argued in detail. The interaction parameter in the solution

-p

mixture (Rb) and at the interfacial surface (βσ) is constantly achieved negative in the entire cases. Activity coefficients of the mixed micellar system (f1Rb (BTC) and f2Rb (AMHCl)) and

re

mixed monolayer (f1σ (BTC) and f2σ (AMHCl)) were forever less than one telling the nonideal

lP

behavior of systems. Various surface parameters have been estimated along with various thermodynamic parameters have also been assessed. Fluorescence measurements were carried

na

out to evaluate further results for the above-stated system in all studied media. At 298.15 K, the aggregation number (Nagg) values computed by means of pyrene (PY) as a fluorescent probe

ur

along with many other related parameters were also estimated. Keywords: Amitriptyline hydrochloride; Benzethonium chloride; Urea; Fluorescence; Mixed

Jo

micellization parameters

2

Journal Pre-proof 1. Introduction In fundamental along with the applied field, surfactants participate as an imperative responsibility [1,2]. Surfactants are also employed in numerous biochemical along with pharmacological systems as well as it is also utilized for solubilization of hydrophobic substances such as drugs [3,4]. Surfactant particles are primarily adsorbed at the air-solvent interface in the aqueous or non-aqueous solvent [1,2]. On beyond an assured minimum concentration surfactant monomers self-aggregates into a particular shape entitled micelle owing to their amphiphilic character and concentration beyond which this phenomenon starts is called

of

cmc [5-8]. As compared to singular surfactant micelles, mixed micelles of employed surfactants

ro

possibly will demonstrate significant to lessen the quantity along with the expenditure of employed surfactants, in addition, to also decrease their environmental impact [2,9-12]. By

-p

means of this perspective, appliances of mixed micellar systems were utilized recently since mixtures of surfactants display outstandingly unusual as well as superior characteristics than

re

singular constituents [9-12]. The exploration of the bulk solution, the air-solvent interface as well

lP

as thermodynamic properties of studied mixed systems, both in presence/absence of additives, can grant significant information regarding constituents-constituents along with constituents-

na

solvent interactions [1,13].

Akin to most of the surfactants, several amphiphilic drugs have been found to show usual colloidal behavior and form assembly into micellar form via depressing the surface tension but at

ur

a much higher concentration than usual surfactants [1]. Nearly all drugs facing numerous

Jo

unwanted effects because always for the application of drugs for any purposes a controlled released system is required since this system must have the capability to attain their therapeutic targets along with to discharge the employed drug in an organized way [14,15]. Apart from this, a few drugs are facing solubility problems, therefore, their little fraction of the taken drug contacts through the targeted site causing a decrease in the efficiency of drugs [16]. Within this perspective, the employ of surfactant micelles shows various benefits than further options of drug carriers. Micelle is thermodynamically additional stable, and it formed spontaneously towards both dissociation as well as an association [17]. An additional benefit of micelles is that it easily solubilizes poorly soluble hydrophobic drugs along with also enhances drug bioavailability. Surfactants also form mixed micelles with amphiphilic drugs, so lessen in resultant cmc of systems occur. On the other hand, its occurrence in formulations sources

3

Journal Pre-proof numerous unwanted side outcomes [18,19]. This reveals that the requirement of various other additives which can be employed as carriers. Herein, an antidepressant drug amitriptyline hydrochloride (AMHCl) is utilized (Scheme 1). AMHCl has a rigid, relatively planar tricyclic ring system with a small alkylamine side chain having a terminal N atom (Scheme 1). The central ring of the AMHCl is seven members. Owing to the presence of alkyl amine group on AMHCl monomers proposes them to assemble into the micellar form as like of most of the surfactant did, when concentration of drug surpasses the cmc in aqueous or non-aqueous solvent, however, micelles form by drug monomers is small in size

of

roughly around 15-20 molecules per micelles as compared to usual surfactant [1,3]. This

ro

category of drugs is utilized for the cure of depression but when utilized at a small quantity they can only lessen or break the pain. AMHCl possibly will assist to get better mood along with

-p

feelings of happiness or comfort, relieve worry, as well as enhance the level of energy, the Investigation of drug-surfactant interaction has obtained enhanced concentration recently on

re

account of the widespread application of the stated system in the practical field [20-22]. This

lP

drug is used to reduce body pain as well as discomfort, along with the support you get a decent night’s sleep. These types of drugs work by growing the quantity of serotonin your brain creates.

na

It is a chemical, worked as a neurotransmitter, that the brain guides out to nerves in the human body.

Benzethonium chloride (BTC) compounds belonging to the group of quaternary

ur

ammonium salts with antimicrobial and antiseptic activity can be equally well, regarding their

Jo

structure and properties, regarded as surfactants (Scheme 2). This surfactant is utilized as an anticancer agent containing precise activity to kill the head/neck cancer [23,24]. Owing to their surface activity, BTC can trap hydrophobic materials such as hydrophobic drugs inside the micellar core or Stern layer [25]; this means BTC can work as a drug delivery representative. It is also found in cosmetics (powdery appearance on the skin and hair) and toilettes, such as mouthwashes, anti-itch ointments, and antibacterial moist towels. Still another utilization of benzethonium chloride can be found in the food industry where it is used as a surface disinfectant [26]. Herein in the current study, we have reported the mixed aggregation behavior of drug AMHCl (cationic) and BTC (cationic) mixed systems in five various ratios in different media. Up to now, no research has been accounted in the literature for aggregation behavior of AMHCl

4

Journal Pre-proof and BTC mixed systems in aqueous and in the occurrence of NaCl/UR as much as our information. Tensiometric measurements have been performed to determine the cmc of singular and mixed systems in addition to various related parameters. Different theoretical models were employed to assess various micellar and surface parameters. The salt and UR decrease and increase respectively the value of cmc of drug and extensively influence the drug activity in the human being since these compounds (salt/UR) are present in enough amounts in body fluid. Further fluorescence measurement has been utilized to evaluate aggregation number (Nagg) and

of

further allied parameters.

ro

2. Experimental section 2.1. Materials

-p

All preliminary chemicals utilized in the current study are given in Table 1. All employed substances are analytical grades and utilized as obtained from the company. Double refinery

re

water was consumed all over the study for the preparation of the solution. The specific

lP

conductivity of employed water is around 1 to 6 µS.cm-1. The mixtures of AMHCl and BTC in diverse ratios were achieved via an amalgamation of exactly weighing the quantity of both

2.2. Techniques

na

ingredients.

ur

2.2.1. Measurements of surface tension (ST)

Jo

Surface tension (γ) values of current systems in all media were evaluated through an Attension tensiometer, Sigma 701 (Germany) model and this instrument determines the γ value via ring detachment method. At 298.15 K, the values of γ of the singular in addition to their mixed system in different considered ratios were assessed by means of adding stock solutions in diverse chosen media (water, NaCl or UR). Analogous procedures for the measurements of γ value were repeated until γ values of the system under study happen to constant. The cmc values of singular and mixed systems in all studied media were attained by way of the cut-off point in the plot of the γ versus log concentration (log[C]) of utilized ingredients. The uncertainty limits in obtaining γ value were archived equal to ±0.2 mN m–1. An error in the value of cmc was achieved close to ±3% along with the error in temperature was found around ±0.2 K.

5

Journal Pre-proof 2.2.2. Fluorescence measurements Singular constituents (AMHCl and BTC) together with their mixtures in the entire ratio in different studied media aggregation numbers (Nagg) were determined by using a Hitachi F7000 fluorescence method. For Nagg determination, the entire studied system concentrations were set aside well above their relevant cmc value. Here, for the current study, pyrene (PY) and cetylpyridinium chloride (CePC) is consumed as a probe and quencher correspondingly and all studied system were prepared in PY solution. Excitation, as well as emission slit widths, were put at 2.5 nm and excitation wavelength is position at 335 nm. In conclusion, the emission

of

spectrum was noted between 350 to 450 nm wavelength. Via increasing the CePC in solution

ro

under study, the spectra intensity decreases continuously. Each spectrum illustrates five fine

-p

vibronic peaks from lower to upper wavelengths.

3. Results and discussion

re

3.1. Experimental cmc and ideal cmc (cmcid)

lP

To view the qualitative knowledge regarding the interaction of AMHCl and BTC mixed system in different ratios in bulk solution as well as at air- interfacial surface in all studied solvent, the

na

tensiometric measurements were employed. Fig. 1 illustrates the ST against log [C] of singular constituents (AMHCl and BTC) in all studied solvent at 298.15 K. Fig. 2 depicts the ST against log [C] plot of mixed system in different ratios: (a) AMHCl + BTC in water (b) AMHCl + BTC

ur

in 50 mmol·kg-1 NaCl, (c) AMHCl + BTC in 300 mmol·kg-1 UR solutions. The achieved cmc of

Jo

the current studied system (AMHCl and BTC along with their mixed systems in all ratios) in three different solvents are listed in Table 2. As shown in Figs. 1-2, the breakpoint obtained is characterized by the cmc of the studied systems and also the obtained plot is not showing minima close to the breakpoint, validating the high grades of utilized chemicals [2]. The cmc value of singular drug AMHCl in an aqueous solvent is found 32.36 mmol∙kg–1. Obtained cmc value of AMHCl is illustrating good agreement with prior accounted value [1,27,28] and the value of cmc in case of singular BTC was attained 2.95 mmol∙kg–1 viewing also in fine harmony through reported value [29,30]. Overall, the micellization phenomena depend on two features: (i) electrostatic interactions amongst the mixing amphiphile head groups of the constituents, and (ii) tail-tail hydrophobic interactions in mixed amphiphile system. Herein in our system, employed amphiphiles molecules keep positively charges ions. As a result, in the

6

Journal Pre-proof mixtures of amphiphiles, the primary factor prevents the formation of a mixed micelle, while the second factor supports the formation of the micelles. In our case, cmc values of the studied mixture were found amid the cmc of the pure ingredients’ up to mole fraction (1) of 0.5 of BTC and at 1 = 0.7 and 0.9, the mixtures cmc value was found to be below the cmc value of both employed constituents in all studied solvent. The obtained results noticeably point out that in our system hydrophobic interactions dominate in excess of the electrostatic interactions, as a result, supporting the association phenomena in the mixture of solution. Here in current system, component one or first is always used for surfactant i.e., BTC, therefore, mole fraction (α1) of the

of

first component means it’s for BTC and mole fraction (α2) of the second component means for

ro

drug (AMHCl) and summation of mole fraction is equal to one (α1 + α2 = 1). For individual amphiphiles, the cmc value of AMHCl is found much higher than BTC. As shown from their

-p

schemes, that BTC is the much higher hydrophobic as compared to AMHCl, consequently, BTC starts the formation of the micelles at lesser concentration. This is an accustomed reality that the

re

longer the hydrophobic part of any compound, the lower is the value of their cmc.

lP

Lessens in cmc value of singular constituents (AMHCl and BTC) plus their mixed systems took place in a salt solution, however, studied systems cmc value increases in UR

na

solution (Table 2). Electrolyte decline the cmc of employed constitutes in the pure and mixed

system through the lessening of the electrostatic repulsion amongst the positively charged

ur

head groups (because the repulsion between head groups is the principal cause for delay of the start of aggregation) as well as some shifting of the hydrophobic carbon chain beyond

Jo

aqueous atmosphere [31]. In order that less electrical work is needed for the start of association phenomena in a salt solution, showing the interactions amongst salt and employed components [31,32]. It is found that the presence of UR, an increase in cmc value occurs [33]. The

increase in cmc values in UR solvent is caused by the rupturing ability of the iceberg arrangement; therefore, UR places in the group of H2O structure breaker [34]. UR enhances the cmc owing to reduce in H-bonding. As the H-bonding of solvent (UR + H2O) reduces, UR shows to decrease hydrophobic interactions as well as aggregation capability, in order that timely micelle formation takes place means at somewhat higher concentration. The outcome of H2O structure breakers is somewhat resembling that attributable to enhance in

7

Journal Pre-proof temperature [35], hence an increase in cmc has been observed in the occurrence of UR in the studied system (AMHCl, BTC and AMHCl + BTC in the different ratio). Figs. 1 and 2 show that in case of singular along with mixed systems in all studied solvent, the addition of prepared assured concentration of stock solution into the solvent (water, salt or UR), the lessening of ST value is showed continuing up to a certain level, viewing the encouraging adsorption of the employed constituent in addition to their mixtures at the airsolvent interfacial surface. In the case of mixtures in the employed solvent, as the α1 (BTC) rises in the solution under study, lessening in cmc value were taken place signifying very well

of

interaction amongst the involving components (Table 2 and Fig. 3). As clear from Table 2, the

ro

cmc value of BTC is archived more or less 10 folds lower than AMHCl, accordingly, BTC have spirit to turn out in micellar form instantaneously, and the AMHCl monomers possibly will only

-p

intercalate into micelles of BTC, signifying the formed mixed micelles by mixing of both ingredients are well-off in BTC.

re

With the purpose of test out whether the mixed amphiphiles in the current system act

lP

ideally or not the cmc value in ideal state (cmcid) were theoretically evaluated via the Clint model [36] to guess the cmc of mixture of two constituents called cmcid by a known cmc value of

na

singular component by employing the subsequent equation. (1)

and

values are mole fractions of BTC and AMHCl individually. The

Jo

correspondingly and

ur

In Eq. (1) cmc1 and cmc2 are the cmc of constituents first (BTC) and second (AMHCl), experimentally and theoretically evaluated cmc values (cmc and cmcid) are recorded in Table 2. Eq. (1) discloses the difference amongst ideal and non-ideal mixed systems of amphiphiles. A lesser cmc value of the mixtures from their cmcid value, that is to say, a negative deviation was obtained specifies synergistic or attractive interactions amongst the mixing ingredients, whereas higher cmc value of the mixtures from their cmcid value is called positive deviation denotes the antagonistic or repulsive interactions between the mixing ingredients, while if experimentally and theoretically evaluated cmc approximately were obtained equal to each other (cmc  cmcid) is called ideal mixing. Our obtained data (Table 2) evidently stated that the cmc values were constantly beneath the value of cmcid in all studied solvent showing the synergistic or attractive attractions among the constituents forming mixed micelles due to nonideal behavior. Analogous

8

Journal Pre-proof results had previously been also monitored in the case of drug-surfactant mixtures of varying hydrophobicity [37,38]. The large lessening of cmc is a consequence of the enlarged hydrophobicity of the system via intercalation of drug molecules inside the BTC micelles. In subsistence of electrolyte in a studied mixed system, the more negative deviation was reached means cmc value becomes more away from cmcid than the aqueous system. Whereas reverse phenomena were attained in the subsistence of UR solvent, however, still the system behaves like non-ideal in UR solvent, however, their extent of non-ideality is somewhat decreased as compared to the aqueous system. In conclusion, If the mixed system of amphiphiles does not

of

interact through one another, then the resultant mixture is called ideal mixing and the calculated

ro

cmc of these kinds of mixture called cmcid. If they interact or repel with each other, evaluated cmc will either enhance (antagonistic interaction) or decline (synergistic interaction)

-p

respectively. Herein, the value of cmcid was achieved more as compared with the experimental cmc, representing synergism (attractive interaction) amid drug and surfactant mixtures, that also

re

viewing the nonideal behavior of solution mixtures. Consequently, as a result of attractive

lP

interaction amongst the studied constituents, the value cmcid was found more in comparison to

na

the experimental cmc value in all studied media.

3.2. Mixed micelle study of studied constituents in different solvent The interaction amongst studied mixed systems in different solvents can be additionally

ur

examined by means of Rubingh’s model and it is based on regular solution theory (RST) [39].

Jo

As suggested by Rubingh [39], the micellar composition of ingredient 1 (X1R) i.e., for BTC, along with interaction parameter (βm) of the mixed micelle is computed by means of solving the subsequently coupled equations.

(2) (3) The obtained value of composition of ingredient in mixed micelle by Rubingh’s method [39] can be compared through the micellar composition of ingredient evaluated in the ideal state (

) by concerning Motomura's approximation [40]

(4) 9

Journal Pre-proof The micellar composition of ingredient 1 (

) values and their ideal values (

)

determined from their relevant equations were stated in Table 2 and it is found that their values were increases regularly with an increase in 1 of BTC in the solution mixture in all studied were also attained higher in all cases as compared to employed α1

solvent. The values of

except at the highest α1 value of BTC. The

value was achieved in all cases higher than the

employed α1 value indicating that certainly, their values will be more than

, therefore, mixed

micelles include smaller quantity BTC as probable from the ideal state. The

values were not

demonstrating any defined pattern with 1 in salt or UR solvent, however in UR solvent, their

mixed system occurs than the aqueous system.

-p

parameter

values assessed by an iterative solution of Eq. 3 are exposed in Table 2. The value is exposing the degree of interaction among studied ingredients, but in

re

The

enhances, and so growth in cmc of the

ro

the repulsive interactions, as a result, the value of

of

value regularly decreases having exception at α1 = 0.9 (Table 2). As UR is known for burgeoning

addition, reports the divergence from ideality. In case of ideal mixing,

value is showing the repulsive or antagonistic interactions, while negative

lP

zero. Positive

supposes null means

value is entailing an attractive or synergistic interaction amongst the mixing ingredients [41]. In values were attained negative over the entire range of mole fraction

na

our case, the evaluated

(1) of BTC at the examined temperature, showing the formation of micelle is supported means

ur

the attractive interaction amongst constitutes and their magnitude also increases with 1 viewing

Jo

the interaction amongst constituents increases, means micelle formation is more favored at higher 1 (Table 2). In the current study, the value of

were found in the range of –12 to –1

viewing strong attractive interactions amongst the studied constituents in all solvent (Table 2). The type of interaction between the constituents possibly will be either attractive interaction or synergism. Synergism in any system is achieved if the resultant cmc of mixed systems were less than singular amphiphiles accompanied by subsequent 2 conditions were also fulfilled [2]: (i) values of

should always below zero, and (ii) |

|

|

|. In

our case, both the above conditions are only fulfilled by AMHCl-BTC mixed system in salt solution at the entire studied of 1 BTC, viewing synergism were found among the AMHCl and BTC mixed system in the salt solution. However, for AMHCl-BTC mixture in aqueous and UR solutions, both above conditions are fulfilled only at a higher mole fraction of BTC (0.5 1 and

10

Journal Pre-proof above), while at 0.1 and 0.3 1 only first condition is fulfilled by the system and fail to follow the second conditions. Therefore, in a mixed system of AMHCl and BTC in water/UR solvent synergism is found only at higher 1 of BTC and attractive interaction are achieved at inferior 1 of BTC. Table 2 also shows that the negative value of

were additionally enhanced in

electrolyte solvent than an aqueous solution at all studied 1 of BTC. As the interaction amongst the charged head groups becomes more owing to the high ionic strength of the studied system in the salt solution, which caused

additional negative [42]. However, as compared with the becomes fewer in UR solution, suggesting that the

of

aqueous system the negative value of

value occurs as UR ties

ro

interaction amongst constituents reduces (Table 2). The decrease in

via the hydrophobic portion of studied constituents, additionally lowers the hydrophobicity of

-p

mixed system, triggering the growth in the cmc value plus the lessening in the values of

re

(Table 2).

Consistent with the Rubingh theory, the activity coefficients values of constituents of first and

*

(

and

) + ) +

ur

The

(

(6)

values with the function of the

Jo

in all studied solvent. The

(5)

na

given below equations: *

) within the mixed micelle are assessed using the

lP

(BTC) and second (AMHCl) (

and

of BTC thus attained are recorded in Table 2

values are found below one over the whole composition

range representing non-ideal behavior along with attractive interactions amongst the constituents. Table 2 also shows that the

(BTC) value was higher as compared with

(AMHCl) which

draws attention to a more portion of BTC in the mixed micelle than AMHCl in all studied solvent.

3.3. Characteristics of AMHCl-BTC interaction at interfacial surface Herein, the evaluated values of cmc attained from ST were achieved below from those calculated theoretically called cmcid; showing that the synergism or attractive interaction was detected during the formation of mixed micelle. Akin to different parameters regarding mixed micelles formation, numerous air-solvent interfacial parameters of the studied system of

11

Journal Pre-proof AMHCl-BTC for the entire compositions has been also assessed in the current study. The quantity of monomers is always achieved higher at the air-solvent interfacial surface than inside of solution. The surface excess concentration (

) at the air-solvent interfacial surface which

indicates the number of employed molecules adsorbed at the surface can be analyzed using the Gibbs adsorption equation as specified below [43,44]:

*

– The

(mol m–2)

+

(7)

stated as how much the air-solvent interfacial surface is shielded via amphiphiles

of

dropping the ST of solvent at cmc whereas i is the number of pieces of each amphiphile

ro

monomer at the air-solvent interfacial surface after dissociation, R and T keep the traditional meaning. The number of pieces (i) contributing at the interfacial surface for studied mixed

-p

system of AMHCl and BTC in all solvent can be estimated using the equation, [45], while for the case of singular constituents, i.e., i = 2.

is the composition of

re

the first constituent i.e., BTC in the mixed monolayer at the interfacial surfaces and their values

lP

are given in Table 3 and will discuss in the latter part of the manuscript. The minimum area occupied by each amphiphilic particle (

na

ensuing equation [43,44].

) is computed via the

(Å2)

ur

(8)

NA shows the Avogadro number. The minimum area engaged via sole amphiphilic particle in ) of the mixtures is assessed by engaging Eq. (9)

Jo

ideal condition (

Amin,1 +

Amin,2

(9)

Amin,1 is the Amin of singular BTC and Amin,2 is the Amin of singular AMHCl. The evaluated values for singular and binary mixed systems in all studied solvent are presented in Table 3. The extent of

value for the case of binary mixtures of amphiphiles of

identical charge in any solvent was depended on two conflicting contributing features [46]: (i) hydrophobic interactions amid the hydrocarbon length of employed components, (ii) head grouphead group repulsive interactions amongst the employed constituents. Longer the

value,

greater is the surface activity. With the increase in the α1 of BTC in the mixed system, there is no specific trend were detected but the overall increase of

12

values were observed but their

Journal Pre-proof values were obtained lower than both singular employed constituents. Logically have the opposite trend than that of

values. The values of

or

values

propose whether the

employed ingredients monomers are closely or loosely crowded at the air-solvent interfacial surface. The values of

of a mixed system of AMHCl and BTC in all studied solvent were

achieved to lower than the values of achieved higher than the value of

. The values of

for AMHCl-BTC mixtures were

of singular components, because of the bulky along with

more hydrophobic sizes of presently utilized components produce steric deterrent. The is achieved higher in case of singular AMHCl than singular BTC, means the reverse

trend was obtained for

value in all studied solvent. In presence of salt/UR the

or

of

value

ro

value does not display any consistent movement in the entire cases.

The efficiency of air-solvent interfacial surface adsorption is projected via values of pC20

-p

[2]. The higher efficiency of adsorption more is the reduction in ST by the employed constituents. The values of C20 are analytically described as the lessening of ST by the employed

lP

re

ingredient to 20 mN.m-1. The pC20 value is computed via the Eq. (10) [2]. (10)

The evaluated values of pC20 of the entire studied system in all solvent are depicted in Table 3.

na

In the entire studied solvent, the pC20 value of singular BTC was achieved more as compared with singular AMHCl viewing that the greater surface activity of BTC, again confirming that

ur

why cmc value of BTC is more than AMHCl. Table 3 also shows that the pC20 values rise through the increase of 1 of BTC but not in all cases showing the good surface activity of mixed

Jo

system in all studied solvent and their values were achieved much higher than singular AMHCl pC20 value but nearby to pC20 value of BTC. The pC20 value of individual BTC and mixed system were increased than aqueous system except for the value of singular AMHCl which value was found nearly the same in aqueous and salt system (Table 3). The obtained of this phenomenon is showing that in salt solution adsorption efficiency at the air-solvent interface is increased demonstrating the compaction of the employed mixed ingredients means they have better surface activity than aqueous system but, in UR solvent, the pC20 value is not showing any consistent trend. The surface pressure at cmc (πcmc) which defines the maximum reduction of ST can be attained using Eq. (11) [47,48].

13

Journal Pre-proof –

(11)

In Eq. (11) γ0 and γcmc are the ST of employed solvent and ST at cmc of the studied system of singular AMHCl and BTC and AMHCl-BTC mixed system correspondingly. The evaluated value of γcmc and πcmc are given in Table 3. Higher value of πcmc of solution shows the higher ability to the reduction of ST. The πcmc value for AMHCl is lower than BTC, viewing that BTC possesses the higher capability for the reduction ST of solvent and their values were comparatively the same for the dissimilar 1 of BTC but closer the πcmc value for AMHCl of BTC in all studied solvent.

) in addition to the interaction parameter (

ro

water interfacial surface (

of

In similarity with Rubingh concept [39], the employed monomers composition at the air) in the systems of

AMHCl and BTC in all studied solvent were also determined by means of the Rosens method

-p

[2,49] using subsequent equations.

re

(12)

lP

(13)

na

where C is the concentration of AMHCl-BTC mixture, C1 is the concentration of BTC and C2 is the concentration of AMHCl at monolayers in all studied solvent and

specifies the

ur

composition of the first component (BTC) at the interface. The assessed values of

and

were exposed in Table 3. Like the behavior of βm in case of a mixed micellar solution, for the

Jo

case of a mixed monolayer system, the βσ is found close to or equal to zero for ideal mixed monolayer formation means the no interaction amongst employed constitutes. In any case for βσ less than zero showing the synergistic interaction amongst the employed constituents, however for βσ value more than zero viewing the antagonistic interaction among ingredients. All assessed

in addition to βσ values are revealed in Table 3. The

value is not

demonstrating any exact trend through the change in 1 of BTC but over their values increases with 1 because of the dissimilar structure of employed ingredients in all studied solvent. The values were achieved higher than corresponding all 1 of BTC except at 0.9 1 showing the high involvement of BTC in mixed monolayer. Average average value of

value was attained higher than the

signifying that the contribution of BTC is more at mixed monolayer than

14

Journal Pre-proof mixed micelles. By means of a higher degree of hydrophobicity of the BTC as compared to AMHCl, it prefers the interface, consequently, a higher quantity BTC is present at the interface. The

value is attained more in NaCl solvent at all studied 1 of BTC than water solvent

inspecting that salt declines the repulsive interaction amongst the head group of utilized ingredients, therefore the composition of BTC in mixed monolayer increases in salt solution than aqueous system (Table 3). Instead in the UR solvent, the

value declines as compared to UR

free solution having exception at 1 = 0.1 and 0.3, as UR, boosts the repulsions amongst studied ingredients mixture, producing the lessening of

value (Table 3).

of

The achieved values of βσ were found in all studied systems and solvents telling

ro

synergism or attractive interactions amongst the ingredients of mixed monolayer at the interfacial surface and the composition of BTC is achieved higher than AMHCl but their value did not view

-p

any regular trends via enhancing in the 1 of BTC in all mixed systems and solvents (Table 3).

re

The average value of βσ in all studied systems was achieved higher than the average value of βm showing the formation of close-fitting pack mixed monolayer means stronger interaction

lP

amongst the constituents were found at the air-solvent interface than mixed micelles (Tables 23). In NaCl/UR solvent, the value of βσ was not achieved in any proper trend.

na

The synergism phenomena in any mixtures are not only rested on the asset of interaction amongst employed constituents, but this phenomenon is also depending on the substantial

ur

characteristics of both singular employed species of mixtures [50]. Consequently, the synergism in ST reduction efficiency is attained, the moment at which entire concentration of the mixture of

Jo

constituents desired to decline the ST of pure solvent (i.e. water) to a decided ST value (20 mN.m-1) below that of a singular constituent. Apart from this, the synergism phenomena in the system are confirmed once the following both assumed conditions are satisfied [2]: (i) the value of σ should be below zero and (ii) magnitude of βσ should obtain to more than the value of ln(C1/ C2). Table 3 shows that our studied systems follow both conditions in all solvent except 0.1 1 of BTC looking synergism behavior of the studied system at air-solvent interfacial surface. Therefore, the obtained values of βσ recommend the synergism in the ST reduction efficiency. Another parameter that also telling the nonideal conduct of the mixed monolayer is called activity coefficient.

The activity coefficient (f1σ (BTC) and f2σ (AMHCl)) values were

anticipated through using Eqs. (14) and (15):

15

Journal Pre-proof (14) (15) Using above both equations, the activity coefficients (f1σ and f2σ) are achieved below unity in studied systems of different solvent which direct the attractive (interaction amongst employed constitutes were achieved stronger than interaction amid singular constituents) nonideal behavior (Table 3). The f1σ (BTC) is found higher than f2σ (AMHCl) showing the higher

of

contribution of BTC in mixed monolayer in all studied solvent systems.

3.4. Thermodynamics study

ro

The achieved cmc value of the system is often engaged in acquiring info regarding hydrophobic as well as head group interactions existing mixture constituents (AMHCl and BTC)

-p

in all employed studied solvent. As said by the equilibrium model for micellization, ) of micellization, for the case of

re

thermodynamic parameters for instance Gibbs free energy (

singular ingredients (AMHCl and BTC) along with the mixed system in various ratios in all

lP

studied solvent, can be examined through using Eq. (16) [51-53].

na

Xcmc is the ingredient cmc expressed in mole fraction. The evaluated

(16) values of the studied

system in all solvent are given in Table 4. The values of ∆Gom were constantly achieved negative

ur

in all cases signifying the micelle or mixed micelle formation phenomena is spontaneous in

Jo

character. The value ∆Gom in case singular AMHCl was achieved in good agreement with earlier stared value along with near to other antidepressant drugs [1,27,28,54]. The ∆Gom value of BTC is also found in the same range as the literature data [30,55]. The value of was achieved more with AMHCl

of singular BTC

value viewing the higher spontaneity and hydrophobicity

of BTC as compared with a drug (Table 4). Table 4 also depicts that the magnitude of ∆Gom value increases continuously with enhance in 1 of BTC, the occurrence of this phenomenon telling that the spontaneity of mixed micelles formation in the mixed system rises with the increase of 1 of BTC in the solution mixture in all studied solvent. The values of

for mixed

micelles formation of AMHCl and BTC mixture in the entire studied solvent were achieved more negative than the value of

of singular AMHCl aggregation at all 1 of BTC, observing that

mixed system is more spontaneous than singular AMHCl. At higher 1 of BTC, the negative

16

Journal Pre-proof values of mixtures were found higher than the

value of both employed constituents

(Table 4). In attendance of NaCl in all studied systems (pure and mixed), the value of

turn into

more negative value as compared with water solvent, representing that system become more spontaneous, hence, mixed aggregation starts at an inferior concentration (Table 4). On the other hand, the

negative values decline in UR solvent in all cases, telling that, the system

becomes less spontaneous to some level than the aqueous system. Another thermodynamic parameter called standard Gibbs free energy of adsorption ) were too evaluated for investigation of the aggregation behavior of the pure and mixed

of

(

ro

system in all studied solvent using Eq. (17) [56,57]:

) values of the current employed system in all studied solvent were

-p

The attained (

(17)

values were achieved negative viewing that adsorption

re

exposed in Table 4. The

phenomena occurring in the systems are physically spontaneous and their negative value was value. This more negative value of

lP

constantly acquired higher than

than

showing that the adsorption phenomena are more favorable (occurs first) than micellization

na

behavior and some effort must be done in bringing the employed molecules from the solution surface to the micellar state [58]. The

value of BTC is achieved more negative than the

ur

value of AMHCl, telling that the BTC is more surface active than singular AMHCl. The

Jo

mixed system of AMHCl and BTC are showing more

value as compared to the employed

individual ingredients, viewing that adsorption phenomena are additionally favorable in the mixed monolayer. In UR solvent, the

values are not viewing any precise trend in e case of

singular and mixed components; but, in NaCl solvent, the value of

for mixtures were

achieved higher negative signifying that adsorption phenomena in NaCl solvent are moreover spontaneous (Table 4). The minimum free energy (Gmin) of the interface is another thermodynamic parameter for the working out of synergism in case of individual constituent monolayer along with mixed constituent monolayer film in all studied solvent at equilibrium means at or above maximum adsorption is determined through employing Eq. (18) [59,60]: (18)

17

Journal Pre-proof The values of Gmin disclose the lenience of the formation of mixed monolayers via transporting the monomers from the bulk solution. The value of Gmin in the case of individual and mixed systems in all studied solvent was attained positive as well as lower in magnitude (Table 4) and their lower value indicates the exceedingly stable surface is formed; consequently, larger surface activity is obtained. Table 4 also shows that the Gmin values were not showing any definite propensity through enhancing of α1 of BTC in all studied solvent. The values of excess Gibbs energy of the mixed micelle (

) formation was attained via the Eqs. (19) and (20) [61-65].

(

)

]

The assessed values of

(19) (20)

-p

ro

[

of

monolayer (

) in addition, mixed

and

of the studied mixed system are reported in Table 4 in all

re

solvent. A negative value of excess Gibbs energy agrees that the interactions amongst employed constituents in the mixed micelles and monolayer film are gained more attractive means showing

lP

higher stability than the association of singular constituents, nevertheless for the positive value of excess Gibbs energy the opposite results were attained [2]. In all systems, both excess Gibbs

na

energy in all solvent was attained negative at all α1 of BTC, viewing the formed mixed monolayer and mixed micelles are achieved higher stable and spontaneous in nature in contrast

ur

to the formed singular ingredient’s micelles/monolayer. The negative value of both excess Gibbs energy increases via enhancing in α1 of BTC, showing the stability of the studied system rises by

Jo

increasing α1 of BTC in solution mixtures in all solvent. In the case of

only, in the

occurrence of salt, their magnitude increases, indicates that stability of mixtures increases in the salt solution, since it declines the electrostatic repulsion amongst the studied ingredient headgroups [66] and in UR solution their negative value somewhat decreases but not in large amount but in case of

values are not looking any specific behavior in UR/NaCl solvent.

3.5. Packing parameters The surfactants aggregate in various morphologies such as spherical, ellipsoidal, rod shapes, disk-like, as a result of this they make cubic, hexagonal, lamellar and cage structures. These depend on the packing of surfactants in the formation of micelle. First time in the

18

Journal Pre-proof literature Tanford and Israelacgvili et al. [67,68] explained this geometrical packing of surfactants. The association of surfactant monomers into micelles, bilayers, and vesicles due to the two opposing forces: (i) hydrophobic consequence of hydrocarbon portions (try to carry the monomers close to each other), (ii) solvation of the head groups (try to keep away hydrophilic part). If the surfactant molecules are ionic nature another factor (electrostatic repulsion of the head groups) is associated with the increase the effective head group is per molecule. According to Israelachvili et al., the shape of aggregation depends on three parameters: the volume of the hydrophobic portion (V0), length of the hydrophobic part (lc) along with the operative head group

of

area of the employed molecules. The volume and length can be computed by the Tanford

In Eqs. (21) and (22),

(21) (22)

re

-p

ro

formula [68]

is the number of carbons in the linear alkyl chain. The critical packing

lP

parameter (P) is figured via the Israelachvili equation [67]: (23)

na

The values of P describe the possible geometry of the aggregated structure formed in the solution. The accurate evaluation of head group area at the surface of micelles is difficult [2], as value attained from the surface tension method rather than the

ur

a result, we have employed

Jo

head group area as declared previously [2]. The values of P for spherical, cylindrical and lamellar amphiphiles are ~0.33, 0.33 to 0.5 and 0.5 to 1, respectively. Table 5 viewed that the P values of mixed systems at all mole fractions decrease with UR indicating the formation of smaller micelles. The values of p for the mixed system in the attendance or absence of salt and UR have values less than 0.5 confirm spherical or cylindrical shape micelle.

3.6. Aggregation number and Stern-Volmer constant The result attained by the surface tension measurements can be further explored based on the quenching of a probe by an appropriate quencher under steady-state circumstances. In our present study, we used pyrene (PY) having five vibronic peaks as a probe and a cationic surfactant CePC as a quencher. Under study state conditions the aggregation number (Nagg) of

19

Journal Pre-proof singular constituents along with their mixtures in diverse ratios have been computed using PY (probe) and CePC (quencher). Eq. (24) is used to determine the Nagg values [69,70]:

( ) In Eq. (24), linear plot of

(24) and [Q] depicts total surfactant and quencher concentration. The slope of the ( ) vs. [Q] has been used to determine the values Nagg. Fluorescence spectra of

10−6 M PY of (a) singular BTC and (b) BTC (0.5) + AMHCl (0.5) mixed system at different CePC concentrations in the aqueous micellar system is shown in Fig. 4. The values of Nagg are

of

exposed in Table 6. The attained Nagg value discloses that for mixed system at all 1 were found

ro

to be higher than the pure drug Nagg value but at 1 = 0.7 and 0.9, value of Nagg turn out to be more as compared with both employed pure constituents, observing the interaction amongst

-p

constituents rises within mixed micelles in the entire studied system accompanying to probably

re

bigger size of micelles formation. For AMHCl/BTC mixed system the Nagg values rise with the α1 of BTC. The archived outcomes are consistent with the surface tension outcomes that the

lP

AMHCl + BTC mixed micelles comprise more BTC than AMHCl. On increasing the cationic surfactant (BTC) concentration in the mixed micelle increases the hydrophobic interaction

na

increase result in the formation of larger micelle. In salt media, the Nagg values increases at all mole fraction of BTC, simply stated that charge neutralization takes place that lessens the

ur

repulsion amongst the charged parts of employed constituents and accordingly, permits aggregation having extra employed constituents’ monomers. In UR solvent, values of Nagg of

Jo

singular compounds along with their mixtures decreases, because UR rises the repulsions amongst the head groups in case of singular and mixed systems that leads to inferior Nagg and higher the cmc values.

The strength of the hydrophobic atmosphere is computed by means of Stern-Volmer binding constant (Ksv) [71,72]. (25) The values of Ksv are listed in Table 6. The Ksv values decrease with increasing AMHCl, indicates the formation of less compact micelles. Higher the values of Ksv suggest that the attendance of both PY and CePC in the durable hydrophobic atmosphere result in increased quenching.

20

Journal Pre-proof 3.6.1. Microenvironment The fluorescent quencher intensity of first (I1) and third (I3) peaks depicts a knowledge regarding the micropolarity (I1/I3) of the studied singular and mixed solutions. PY is showing lower solubility in a polar system than the non-polar hydrocarbon system, resources that PY is departed from the polar aqueous system towards the hydrocarbon province means inside the micelles. If the value of

I1/I3 is beneath one income that the probe is in the nonpolar solvent

while the values of I1/I3 more than 1 income the atmosphere is polar. It is confirmed from the data (Table 6) most of the values are less than 1.5 suggest pyrene is solubilized in a polar

of

environment (alcohol). For the case of mixtures of AMHCl and BTC, the value of I1/I3 did not

ro

show any specific trend through enhancing the α1 of BTC. In NaCl solution, the I1/I3 value for individual constituents (AMHCl and BTC) is achieved less as compared with the aqueous

-p

solution, viewing that the polarity of singular ingredients decreases in presence of the electrolyte (Table 6).

(26)

lP

re

The dielectric constant (D) of the studied systems is computed via the Eq. (26) [73].

The evaluated D values are listed in Table 6, and values were archived close to the D value for

na

alcohol [74], again confirm that the probe is in a short polar environment.

as:

(27)

Jo

∑

ur

Turro et al. [73] gave the following relation for ideal values of dielectric constant (Dideal)

Table 6 data confirmed that the experimental values (D) and ideal values (Dideal) are not the same. This deviation is because of the attractive interaction inner side of the micelle.

4. Conclusion Current study comprises the tensiometry and spectroscopic investigation of the cationic drug AMHCl and cationic surfactant BTC mixed systems in three different solvents at T = 298.15 K. The cmc values were evaluated through tensiometeric technique and were further used to acquire various physio-chemical parameters. Surfactants are usually employed as drug carriers. Consequently, it is significant to have information regarding the outcome of surfactant on the aggregation behavior of amphiphilic drugs. Mixed systems of employed ingredients

21

Journal Pre-proof (AMHCl+BTC) showing good non-ideal behavior, as specified via the values of cmc and cmcid since the cmc values are constantly achieved to be lower than cmcid values. Contribution of BTC (X1Rb and X1σ), computed from Rubingh and Rodenas theories, demonstration higher involvement of BTC in mixed micelles as well as in mixed monolayers. The values of Rb and βσ emerge negative in all solutions in all solvent suggesting the synergism or attraction interactions among constituents in mixed micelles/mixed monolayers. The obtained negative ∆Gom values validating the micellization and mixed micellization are spontaneous phenomena, however, a negative

and

values indicate the high stability of mixed systems. The magnitude of

of

∆Gom increased is salt solvent while their values decrease in the UR solvent than the aqueous

ro

system. The value of Nagg was increasing continuously through raising the α1 of BTC in a mixed system of aqueous solution and obtained to be more in salt solution while in UR their value

-p

decreases.

re

Acknowledgment

lP

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant No. (DF-865-130-1441). The authors, therefore, gratefully

Jo

ur

na

acknowledge DSR technical and financial support.

22

Journal Pre-proof References [1] D. Attwood, A.T.

Florence, Surfactant systems. Their chemistry, pharmacy and

biology, Chapman and Hall, New York, 1983. [2] M.J. Rosen, Surfactants and Interfacial Phenomena, third ed. John Wiley & Sons, New York, 2004. [3] S. Schreier, S.V.P. Malheiros, E. de Paula, Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects, Biochim. Biophys. Acta 1508 (2000) 210-234.

of

[4] C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Experimental and

ro

computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Delivery Rev. 46 (2001) 3-26.

-p

[5] D. Kumar, M.A. Rub, Catalytic role of 16-s-16 micelles on condensation reaction of ninhydrin and metal-dipeptide complex, J. Phys. Org. Chem. 32 (2019) e3918. Kumar,

M.A.

Rub,

Role

of

cetyltrimethylammonium

re

[6] D.

bromide

(CTAB)

lP

surfactantmicelles on kinetics of [Zn(II)-Gly-Leu]+ and ninhydrin, J. Mol. Liquids 274 (2019) 639-645.

na

[7] D. Kumar, M.A. Rub, Synthesis and characterization of dicationic gemini surfactant micelles and their effect on the rate of ninhydrin–copper-peptide complex reaction, Tenside Surfactant Deterg. 55 (2018) 78–84.

ur

[8] D. Kumar, M. A. Rub, Study on the reaction of ninhydrin with tyrosine in gemini

Jo

micellar media, RSC Adv. 9 (2019) 22129-22136. [9] A. Srivastava, H. Uchiyama, Y. Wada, Y. Hatanaka, Y. Shirakawa, K. Kadota, Y. Tozuka, Mixed micelles of the antihistaminic cationic drug diphenhydramine hydrochloride with anionic and non-ionic surfactants show improved solubility, drug release and cytotoxicity of ethenzamide, J. Mol. Liq. 277 (2019) 349–359. [10] N.C. Christov, N.D. Denkov, P.A. Kralchevsky, K.P. Ananthapadmanabhan, A. Lips, Synergistic sphere-to-rod micelle transition in mixed solutions of sodium dodecyl sulfate and cocoamidopropyl betaine, Langmuir 20 (2004) 565–571. [11] N. Fatma, M. Panda, Kabir-ud-Din, Mixed micellization of novel cationic ester-bonded gemini surfactants: Investigations by conductometric and tensiometric measurements, J. Mol. Liquids 219 (2019) 959-966.

23

Journal Pre-proof [12] 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. Liquids 238 (2017) 389-396. [13] A. Pal, R. Punia, Mixed micellization behaviour of tri-substituted surface active ionic liquid and cationic surfactant in aqueous medium and salt solution: Experimental and theoretical study, J. Mol. Liquids 296 (2019) 111831. [14] K.E. Uhrich, S.M. Cannizzaro, R.S. Langer, K.M. Shakesheff, Polymeric systems for controlled drug release, Chem. Rev. 99 (1999) 3181-3198.

of

[15] Y. Jin, T. Li, P. Ai, M. Li, X. Hou, Self-assembled drug delivery systems: 1. Properties

ro

and in vitro/in vivo behavior of acyclovir self-assembled nanoparticles (SAN), Int. J. Pharm. 309 (2006) 199-207.

-p

[16] S.R. Vippagunta, W. Zaren, S. Hornung, S.L. Krill, Factors Affecting the formation of eutectic solid dispersions and their dissolution behavior, J. Pharm. Sci. 96 (2007) 294-

re

304.

lP

[17] R.J. Hunter, Introduction to Modern Colloid Science, Oxford Univ. Press, Oxford, 1993. [18] J.D. Adams, K.P. Flora, B.R. Goldspiel, J.W. Wilson, S.G.I. Arbuck, Taxol: a history of

na

pharmaceutical development and current pharmaceutical concerns, J. Natl. Cancer Inst. Monogr. 15 (1993) 141-147.

[19] K. Woodburn, D. Kessel, The alteration of plasma lipoproteins by cremophor EL, J.

ur

Photochem. Photobiol. B 22 (1994) 197-201.

Jo

[20] M.A. Rub, N. Azum, F. Khan, A.M. Asiri, Aggregation of sodium salt of ibuprofen and sodium taurocholate mixture in different media: A tensiometry and fluorometry study, J. Chem. Thermodynamics 121 (2018) 199-210. [21] D. Kumar, S. Hidayathulla, M.A. Rub, Association behavior of a mixed system of the antidepressant drug imipramine hydrochloride and dioctyl sulfosuccinate sodium salt: Effect of temperature and salt, J. Mol. Liquids 271 (2018) 254-264. [22] M.A. Hoque, M.M. Alam, M.R. Molla, S. Rana, M.A. Rub, M.A. Halim, M.A. Khan, A. Ahmed, Effect of salts and temperature on the interaction of levofloxacin hemihydrate drug with cetyltrimethylammonium bromide: Conductometric and molecular dynamics investigations, J. Mol. Liquids 244 (2017) 512-520.

24

Journal Pre-proof [23] K.W. Yip, X. Mao, P.Y. Au, D.W. Hedley, S. Chow, S. Dalili, J.D. Mocanu, C. Bastianutto, A. Schimmer, F.F. Liu, Benzethonium chloride: a novel anticancer agent identified by using a cell-based small-molecule screen, Clin. Cancer Res. 12 (2006) 5557-5569. [24] H.H. Paradies, U. Hinze, M. Thies, Hydrodynamic studies on benzethonium chloride micelles in dilute aqueous solution, Ber. Bunsenges. Phys. Chem. 98 (1994) 938-946. [25] F.M. Menger, The structure of micelles, Acc. Chem. Res. 12 (1979) 111-117. [26] M. Malmstein, Surfactants and Polymers in Drug Delivery, Ed. Swarbrick James,

of

Pharmaceu Tech, Inc. Pinehurst, North Carolina, USA, 2002, pp. 1–26.

ro

[27] F. Khan, M.S. Sheikh, M.A. Rub, N. Azum, A.M. Asiri, Antidepressant drug amitriptyline hydrochloride (AMT) interaction with anionic surfactant sodium dodecyl

-p

sulfate in aqueous/brine/urea solutions at different temperatures, J. Mol. Liquids 222 (2016) 1020-1030.

re

[28] M.A. Rub, N. Azum, A.M. Asiri, S.Y.M. Alfaifi, S.S. Alharthi, Interaction between in

low concentration

range

in

lP

antidepressant drug and anionic surfactant

aqueous/salt/urea solution: A conductometric and fluorometric study, J. Mol. Liquids 227 (2017) 1-14.

na

[29] J.L. Rodrı´guez, R.M. Minardi, E.P. Schulz, O. Pieroni, P.C. Schulz, The composition of mixed micelles formed by dodecyl trimethyl ammonium bromide and benzethonium

ur

chloride in water, J. Surfact. Deterg. 15 (2012) 147-155.

Jo

[30] A. Karumbamkandathil, S. Ghosh, U. Anand, P. Saha, M. Mukherjee, S. Mukherjee, Micelles of benzethonium chloride undergoes spherical to cylindrical shape transformation: An intrinsic fluorescence and calorimetric approach, Chemical Physics Letters 593 (2014) 115-121. [31] E.J. Kim, D.O. Shah, Cloud point phenomenon in amphiphilic drug solutions, Langmuir 18 (2002) 10105-10108. [32] A. Jakubowska, Interactions of different counterions with cationic and anionic surfactants, J. Colloid Interface Sci. 346 (2010) 398−404. [33] A. Masunav, J.J. Dannenberg, Theoretical study of urea and thiourea. 2. Chains and ribbons, J. Phys. Chem. B 104 (2000) 806-810.

25

Journal Pre-proof [34] M. Manabe, M. Koda, K. Shirahama, The effect of 1-alkanols on ionization of sodium dodecyl sulfate micelles, J. Colloid Interface Sci. 77 (1980) 189-194. [35] R. Bhanumathi, S.K. Vijayalakshamma, Proton NMR chemical shifts of solvent water in aqueous solutions of monosubstituted ammonium compounds, J. Phys. Chem. 90 (1986) 4666-4469. [36] J.H. Clint, Micellization of mixed nonionic surface-active agents. J Chem. Soc., Faraday Trans 1. 71 (1975) 1327-1334. [37] M.A. Rub, N. Azum, S.B. Khan, F. Khan, A.M. Asiri, Physicochemical properties of

of

amphiphilic drug and anionic surfactant mixtures: Experimental and theoretical

ro

approach, J. Disp. Sci. Technology 36 (2015) 521-531.

[38] M.A. Rub, N. Azum, F. Khan, A.M. Asiri, Surface, micellar, and thermodynamic

-p

properties of antidepressant drug nortriptyline hydrochloride with TX-114 in aqueous/urea solutions, J. Phys. Org. Chem. 30 (2017) e3676.

lP

Chem. 87 (1983) 1984-1990.

re

[39] P.M. Holland, Rubingh DN. Nonideal multicomponent mixed micelle model, J. Phys.

[40] K. Motomura, M. Yamanaka, M. Aratono, Thermodynamic consideration of the mixed

na

micelle of surfactants, Colloid. Polym. Sci. 262 (1984) 948-955. [41] S.P. Moulik, S. Ghosh, Surface chemical and micellization behaviours of binary and ternary mixtures of amphiphiles (Triton X-100, Tween-80 and CTAB) in aqueous

ur

medium, J. Mol. Liquids 72 (1997) 145-161.

Jo

[42] O.G. Singh, K. Ismail, Effect of sodium chloride on the aggregation, adsorption and counterion binding behavior of mixtures of sodium dioctylsulfosuccinate and sodium dodecylsulfate in water, Colloids Surf. A 414 (2012) 209-215. [43] Q. Zhou, M.J. Rosen, Molecular interactions of surfactants in mixed monolayers at the air/aqueous solution interface and in mixed micelles in aqueous media:  the regular solution approach, Langmuir 19 (2003) 4555-4562. [44] 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. Solution Chem. 45 (2016) 791803.

26

Journal Pre-proof [45] G.B. Ray, S. Ghosh, S.P. Moulik, Ternary mixtures of alkyltriphenylphosphonium bromides (C12TPB, C14TPB and C16TPB) in aqueous medium: their interfacial, bulk and fluorescence quenching behavior, J. Chem. Sci. 122 (2010) 109-117. [46] R. Sharma, S. Mahajan, R.K. Mahajan, Surface adsorption and mixed micelle formation of surface-active ionic liquid in cationic surfactants: conductivity, surface tension, fluorescence and NMR studies, Colloids and Surfaces A 427 (2013) 62-75. [47] K.S. Rao, T. Singh, T.J. Trivedi, A. Kumar, Aggregation behavior of amino acid ionic liquid surfactants in aqueous media, J. Phys. Chem. B 115 (2011) 13847-13853.

H NMR study of mixed micellization of non-steroidal anti-inflammatory drug sodium

ro

1

of

[48] M.A. Rub, F. Khan, M.S. Sheikh, N. Azum, A.M. Asiri, Tensiometric, fluorescence and

salt of ibuprofen in the presence of non-ionic surfactant in aqueous/urea solutions, J.

-p

Chem. Therm. 96 (2016) 196-207.

[49] M.J. Rosen, F. Zhao, Binary mixtures of surfactants. The effect of structural and

re

microenvironmental factors on molecular interaction at the aqueous solution/ air

lP

interface, J. Colloid Interface Sci. 95 (1983) 443-452. [50] F. Li, M.J. Rosen, S.B. Sulthana, Surface properties of cationic gemini surfactants and

na

their interaction with alkylglucoside or -maltoside surfactants, Langmuir 17 (2001) 1037-1042.

[51] M.N. Islam, T. Kato, Temperature dependence of the surface phase behavior and micelle

ur

formation of some nonionic surfactants, J. Phys. Chem. 107 (2003) 965–971.

Jo

[52] F. Khan, U.S. Siddiqui, M.A. Rub, I.A. Khan, Kabir-ud-Din, Micellization behavior of butanediyl-1, 4-bis(dimethyldodecylammonium bromide) gemini surfactant in presence of organic additives, J. Disp. Sci. Technol. 36 (2015) 83-93. [53] N. Azum, A.Z. Naqvi, M.A. Rub, A.M. Asiri, Multi-technique approach towards amphiphilic drug-surfactant interaction: A physicochemical study, J. Mol. Liquids 241 (2017) 189-195. [54] F. Khan, M.A. Rub, N. Azum, A.M. Asiri, Mixtures of antidepressant amphiphilic drug imipramine hydrochloride and anionic surfactant: Micellar and thermodynamic investigation, J. Phys. Org. Chem. 31 (2018) e3812.

27

Journal Pre-proof [55] J. Oremusová, Z. Vitková, Anton Vitko, Study of micelle properties and thermodynamics of micellization of the benzethonium chloride, Tenside Surf. Det. 49 (2012) 322-329. [56] M.J. Rosen, S. Aronson, Standard free energies of adsorption of surfactants at the aqueous solution/air interface from surface tension data in the vicinity of the critical micelle concentration, Colloids Surf. 13 (198) 201-208. [57] N. Azum, A. Ahmed, M.A. Rub, A.M. Asiri, S.F. Alamery, Investigation of aggregation behavior of ibuprofen sodium drug under the influence of gelatin protein and salt, J.

of

Mol. Liquids 290 (2019) 111187.

ro

[58] A. Zdziennicka, B. Janczuk, Thermodynamic parameters of some biosurfactants and surfactants adsorption at water-air interface, J. Mol. Liq. 243 (2017) 236-244.

-p

[59] G. Sugihara, A.M. Miyazono, S. Nagadome, T. Oida, Y. Hayashi, J.S. Ko, Adsorption and micelle formation of mixed surfactant systems in water. II a combination of cationic

re

gemini-type with MEGA-10, J. Oleo Sci. 52 (2003) 449-461.

lP

[60] N. Azum, M.A. Rub, A.M. Asiri, Bile salt–bile salt interaction in mixed monolayer and mixed micelle formation, J. Chem. Thermodynamics 128 (2019) 406-414.

na

[61] E. Rodenas, M. Valiente, M.S. Villafruela, Different theoretical approaches for the study of the mixed tetraethylene glycol mono-n-dodecyl ether/hexadecyltrimethylammonium bromide micelles, J. Phys. Chem. B 103 (1999) 4549–4554.

ur

[62] D. Kumar, M.A. Rub, Aggregation behavior of amphiphilic drug promazine

Jo

hydrochloride and sodium dodecylbenzenesulfonate mixtures under the influence of NaCl/urea at various concentration and temperatures, J. Phys. Org. Chem. 29 (2016) 394-405.

[63] S. Mahbub, M.A. Rub, M.A. Hoque, M.A. Khan, Mixed micellization study of dodecyltrimethylammonium chloride and cetyltrimethylammonium bromide mixture in aqueous/urea medium at different temperatures: Theoretical and experimental view, J. Phys. Org. Chem. 31 (2018) e3872. [64] D. Kumar, M.A. Rub, Effect of sodium taurocholate on aggregation behavior of amphiphilic drug solution, Tenside Surfactants Deterg. 52 (2015) 464-472.

28

Journal Pre-proof [65] N. Azum, M.A. Rub, A.M. Asiri, Interaction of triblock copolymer with cationic gemini and conventional surfactants: A physicochemical study, J. Dispersion Sci. Technol. 38 (2017) 1785-1791. [66] S. Javadian, H. Gharibi, Z. Bromand, B. Sohrabi, Electrolyte effect on mixed micelle and interfacial properties of binary mixtures of cationic and nonionic surfactants, J. Colloid Interface Sci. 318 (2008) 449-456. [67] J.N. Israelachvili, D.J. Mitchell, B.W. Ninham, Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers, J. Chem. Soc., Faraday Trans. 2 (1976) 1525-

of

1568.

ro

[68] C. Tanford, The hydrophobic effect: formation of micelles and biological membranes, John Wiley & Sons, New York, 1980.

-p

[69] N.J. Turro, A. Yekta, Luminescent probe for detergent solutions: a simple procedure for 673 determination of the mean aggregation number of the micelles, J. Am. Chem. Soc.

re

100 (1978) 5951-5952.

lP

[70] 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.

na

Chem. Eng. Data 62 (2017) 3216-3228.

[71] K.K. Rohatgi-Mukherjee, Fundamentals of Photochemistry, Wiley Eastern, New Delhi, 1992.

ur

[72] M.A. Rub, J.M. Khan, N. Azum, A.M. Asiri, Influence of antidepressant clomipramine

Jo

hydrochloride drug on human serum albumin: Spectroscopic study, J. Mol. Liquids 241 (2017) 91–98.

[73] N.J. Turro, P.L. Kuo, P. Somasundaran, K. Wong, Surface and bulk interactions of ionic and nonionic surfactants, J. Phys. Chem. 90 (1986) 288-291. [74] R.C. Weast, Handbook of Chemistry and Physics, CRC Press, West Palm Beach, FL, 1978.

29

Journal Pre-proof Figure captions Scheme 1. Molecular model of amitriptyline hydrochloride (AMHCl) drug. Scheme 2. Molecular model of benzethonium chloride (BTC). Fig. 1. Surface tension (γ) vs. concentration (C) plots for individual amphiphiles ((a) AMHCl and (b) BTC) in a different solvent at 298.15 K. Fig. 2. Surface tension (γ) vs. concentration (C) plots for AMHCl-BTC mixtures in diverse ratio (different mole fraction of BTC (α1)): (a) aqueous solution, (b) 50 mmol∙kg-1 NaCl, (c) 300 mmol∙kg-1 UR at 298.15 K.

of

Fig. 3. Variation of cmc/cmcid of AMHCl-BTC mixtures against mole fraction (α1) of BTC in the different solvent at 298.15 K.

ro

Fig. 4. Fluorescence spectra of 10−6 M pyrene of (a) pure BTC, and (b) BTC (0.5) + AMHCl

Jo

ur

na

lP

re

-p

(0.5) mixed system at different quencher (CePC) concentrations in aqueous micellar solution.

30

Jo

ur

na

lP

re

-p

Scheme 1.

ro

of

Journal Pre-proof

Scheme 2.

31

Journal Pre-proof

70 Pure AMHCl Pure AMHCl + 50 mmol.kg

65

-1

Pure AMHCl + 300 mmol.kg

60

NaCl -1 UR

mN.m

-1

(a)

55

50

0.8

1.0

1.2

1.4

of

45

1.6

1.8

-p

ro

log [AMHCl] / mmol.kg

-1

Pure BTC

70

-1 Pure BTC + 50 mmol.kg NaCl -1 Pure BTC + 300 mmol.kg UR

re

65 60

lP

50 45 40

ur

35

(b)

na

mN.m

-1

55

30

Jo

-1.5

-1.0

-0.5

0.0

log [BTC] / mmol.kg

Fig. 1

32

0.5 -1

1.0

Journal Pre-proof

65

70

(b)

65

60

60

55

mN.m

BTC

0.1 0.3 0.5 0.7 0.9

50 45

0.5

1.0

1.5

-1.5

-1

-0.5

0.0

log [C] / mmol.kg

-p

70 65

re

(c)

60 55 50

-1.0

of

0.0

log [C] / mmol.kg

ro

-0.5

BTC

lP

-1.0

0.1 0.3 0.5 0.7 0.9

35

0.1 0.3 0.5 0.7 0.9

45 40

na

35

BTC

40

35

-1.5

ur

40

-1

45

mN.m

50

-1

55

Jo

mN.m

-1

(a)

-1.0

-0.5

0.0

log [C] / mmol.kg

Fig. 2.

33

0.5 -1

1.0

1.5

-1

0.5

1.0

Journal Pre-proof

18

cmc of AMHCl + BTC in H2O -1

14

cmc of MHCl + BTC + 50 mmol.kg NaCl -1 cmc of MHCl + BTC + 300 mmol.kg UR id cmc of MHCl + BTC in H2O

12

cmc of MHCl + BTC + 50 mmol.kg NaCl id -1 cmc of MHCl + BTC + 300 mmol.kg UR

16

-1

10 8 6 4

of

id

cmc, cmc / mmol.kg

-1

id

0.2

0.4

ro

2

0.6

-p



Jo

ur

na

lP

re

Fig. 3.

34

0.8

Journal Pre-proof

4000

(a)

[CePC]/mmol.kg 0

Intensity

3000

2000

1.49 x 10

-2

2.97 x 10

-2

4.43 x 10

-2

5.88 x 10

-2

7.32 x 10

-2

8.74 x 10

-2

-1

0 360

380

400

420

440

re lP

1500

1000

1.49 x 10

-2

2.97 x 10

-2

4.43 x 10

-2

5.88 x 10

-2

7.32 x 10

-2

8.74 x 10

-2

ur

na

Intensity

2000

0

[CePC]/mmol.kg 0

(b)

2500

500

-p

ro

wavelength / nm

of

1000

Jo

360

380

400

wavelength / nm

Fig. 4.

35

420

440

-1

Journal Pre-proof Table 1. The source and purity of the employed compounds in the current study. Chemical name

Source

CAS number

Amitriptyline hydrochloride (AMHCl)

Sigma (USA)

549-18-8

Purification methods

Vacuum drying

Mass fraction purity

≥ 0.98

Analytic methods

TLCa

-p

ro

of

Benzethonium chloride Sigma (USA) 121-54-0 NA ≥ 0.98 (BTC) NaCl BDH 7647-14-5 Vacuum 0.98 NA (England) drying Urea (UR) Sigma 57-13-6 Vacuum drying 0.98 HPLCb (Germany) Pyrene (PY) Sigma (USA) 129-00-0 Vacuum drying 0.99 NA Cetylpyridinium Merck 6004-24-6 Vacuum drying NA chloride monohydrate (Germany) (CePC)c a GC, gas chromatography, bHPLC, high performance liquid chromatography (provided by

Anhydrous compound was acquired subsequent to drying the CePC hydrate declared in the

lP

c

re

supplier).

Jo

ur

na

table.

36

Journal Pre-proof Table 2. Various physicochemical parameters for AMHCl-BTC mixtures prepared in different solvent at temperature T = 298.15 K and pressure p = 0.1 MPa.a cmc cmcid X1Rb (mmol·kg-1) (mmol·kg-1) Aqueous system 0 32.36 0.1 13.45 16.20 0.5360 0.3 5.75 8.11 0.6951 0.5 3.76 5.41 0.7499 0.7 2.64 4.06 0.7686 0.9 2.04 3.24 0.7925 1 2.95 50 mmol∙kg-1 NaCl 0 29.75 0.1 5.13 14.30 0.5222 0.3 2.09 7.01 0.6051 0.5 1.33 4.65 0.6396 0.7 0.67 3.47 0.6419 0.9 0.5 2.77 0.6671 1 2.52 300 mmol∙kg-1 UR 0 35.10 0.1 15.48 18.05 0.5285 0.3 6.46 9.16 0.6896 0.5 4.25 6.13 0.7464 0.7 3.02 4.61 0.7682 0.9 2.35 3.69 0.7937 1 3.36 a Standard uncertainties (u) are u(T) = 0.20 K,

X1id

Rb

f1Rb

f2Rb

0.5493 0.8246 0.9164 0.9624 0.9899

-0.75 -1.87 -2.61 -3.82 -5.62

0.8506 0.8412 0.8498 0.8153 0.7853

0.8058 0.4071 0.2315 0.1055 0.0294

-2.40

ro -4.13 -5.70 -6.82 -9.65 -11.89

0.3898 0.4111 0.4125 0.2899 0.2676

0.3245 0.1241 0.0615 0.0187 0.0050

-2.47

-0.62 -1.84 -2.57 -3.71 -5.44

0.8717 0.8364 0.8473 0.8189 0.7931

0.8416 0.4141 0.2381 0.1112 0.0323

-2.35

re

-p

0.5674 0.8349 0.9219 0.9649 0.9906

lP

na

ur

Jo

ln(cmc1/ cmc2)

of

α1

0.5372 0.8174 0.9126 0.9605 0.9894

u(NaCl) = 1 mmol∙kg-1, u(UR) = 2 mmol∙kg-1 and

u(p) = 5 kPa (level of confidence = 0.68). Relative standard uncertainties (ur) are ur(cmc/cmcid) = ±3%, ur(X1Rb/X1id) = ±3%, ur(βRb) = ±3%, and ur(f1Rb/f2Rb) = ±4%.

37

Journal Pre-proof Table 3. Various interfacial parameters for AMHCl-BTC mixtures prepared in different solvent at temperature T = 298.15 K and pressure p = 0.1 MPa.a α1

X1σ

βσ

f1 σ

f2 σ

Γmax 107 (mol m-2)

Amin./ (Ǻ2)

γcmc

πcmc (mN m-1)

pC20

ln(C1/ C2 )

ur

na

lP

re

-p

ro

of

Aqueous system 0 20.13 82.49 42.48 28.52 1.87 0.1 0.5380 -9.33 0.1362 0.0669 8.84 187.78/91.20 34.83 36.17 3.33 0.3 0.6018 -8.83 0.2464 0.0407 8.94 185.66/92.23 35.42 35.58 3.50 0.5 0.7701 -3.42 0.8344 0.1313 9.67 171.62/94.96 35.51 35.49 3.09 -3.06 0.7 0.8518 -3.08 0.9348 0.1081 10.47 158.62/96.28 36.36 34.64 3.14 0.9 0.8336 -5.46 0.8595 0.0224 9.58 173.35/95.99 36.5 34.50 3.30 1 16.82 98.68 36.83 34.17 3.19 50 mmol∙kg-1 NaCl 0 20.37 81.49 43.04 27.96 1.86 0.1 0.7561 -4.20 0.7787 0.0904 5.77 287.72/156.70 34.22 36.78 3.50 0.3 0.8576 -3.99 0.9222 0.0530 6.18 268.36/166.80 33.42 37.58 3.85 0.5 0.8384 -5.68 0.8620 0.0183 6.18 268.06/164.89 33.38 37.62 4.11 -5.48 0.7 0.7845 -8.89 0.6614 0.0041 6.19 267.80/159.52 32.8 38.20 4.40 0.9 0.8595 -8.16 0.8511 0.0024 7.09 234.05/166.98 32.77 38.23 4.36 1 9.17 180.96 32.69 38.31 4.27 -1 300 mmol∙kg UR 0 24.05 69.05 42.43 28.57 1.72 0.1 0.6645 -2.87 0.7236 0.2811 7.22 230.08/109.11 35.76 35.24 2.69 0.3 0.7035 -5.18 0.6336 0.0767 6.51 255.18/111.45 35.15 35.85 3.21 0.5 0.7558 -5.26 0.7304 0.0493 7.12 233.34/114.61 34.11 36.89 3.34 -3.82 0.7 0.7478 -7.22 0.6314 0.0176 6.33 262.24/114.13 35.11 35.89 3.55 0.9 0.8174 -7.12 0.7885 0.0086 6.75 245.90/118.32 36.17 34.83 3.52 1 12.84 129.33 36.78 34.22 3.38 a Standard uncertainties (u) are u(T) = 0.20 K, u(NaCl) = 1 mmol∙kg-1, u(UR) = 2 mmol∙kg-1 and

Jo

u(p) = 5 kPa (level of confidence = 0.68). Relative standard uncertainties (ur) are ur(X1σ) = ±2%, ur(βσ) = ±3%, ur(f1σ/f2σ) = ±4%, ur(Γmax) = ±5%, ur(Amin/Aid) = ±5%, ur(πcmc) = ±2%, ur(pC20) = ±3% and ur(γcmc) = ±2%.

38

Journal Pre-proof Table 4. Thermodynamic parameters for AMHCl-BTC mixtures prepared in different solvent at temperature T = 298.15 K and pressure p = 0.1 MPa.a α1

ΔGom (kJ mol-1)

ΔGoads (kJ mol-1)

Gmin (kJ mol-1)

(kJ mol-1)

(kJ mol-1)

Jo

ur

na

lP

re

-p

ro

of

Aqueous system 0 -18.45 -32.62 21.10 0.1 -20.63 -61.53 39.39 -0.46 -5.75 0.3 -22.73 -62.51 39.61 -0.97 -5.24 0.5 -23.78 -60.46 36.71 -1.21 -1.50 0.7 -24.66 -57.75 34.73 -1.68 -0.95 0.9 -25.29 -61.31 38.11 -2.29 -1.87 1 -24.38 -44.69 21.89 50 mmol∙kg-1 NaCl 0 -18.66 -32.38 21.13 0.1 -23.01 -86.75 59.30 -2.55 -1.92 0.3 -25.23 -85.98 54.02 -3.37 -1.21 0.5 -26.35 -87.16 53.95 -3.89 -1.91 0.7 -28.05 -89.67 52.91 -5.50 -3.73 0.9 -28.78 -82.67 46.19 -6.55 -2.44 1 -24.77 -66.53 35.63 300 mmol∙kg-1 UR 0 -18.25 -30.13 17.65 0.1 -20.27 -69.11 49.56 -0.38 -1.59 0.3 -22.44 -77.54 54.02 -0.96 -2.68 0.5 -23.48 -75.33 47.94 -1.20 -2.41 0.7 -24.33 -81.01 55.45 -1.64 -3.38 0.9 -24.95 -76.53 53.57 -2.21 -2.64 1 -24.06 -50.72 28.65 a Standard uncertainties (u) are u(T) = 0.20 K, u(NaCl) = 1 mmol∙kg-1, u(UR) = 2 mmol∙kg-1 and u(p) = 5 kPa (level of confidence = 0.68). Relative standard uncertainties (ur) are ur(ΔGom) = ±3%, ur(ΔGoads) = ±4%, ur(Gmin) = ±4%, and ur(

39

) = ±5%.

Journal Pre-proof Table 5. Various packing parameter for AMHCl-BTC mixtures prepared in different solvent at temperature T = 298.15 K and pressure p = 0.1 MPa.a

ur

na

lP

re

-p

ro

of

α1 V0 (Å3) lc (Å) P Aqueous system 0 1130.8 25.48 0.54 0.1 2475.8 56.98 0.23 0.3 2475.8 56.98 0.23 0.5 2475.8 56.98 0.25 0.7 2475.8 56.98 0.27 0.9 2475.8 56.98 0.25 1 1453.6 33.04 0.45 -1 50 mmol∙kg NaCl 0 1130.8 25.48 0.54 0.1 2475.8 56.98 0.15 0.3 2475.8 56.98 0.16 0.5 2475.8 56.98 0.16 0.7 2475.8 56.98 0.16 0.9 2475.8 56.98 0.19 1 1453.6 33.04 0.24 300 mmol∙kg-1 UR 0 1077 24.22 0.64 0.1 2475.8 56.98 0.19 0.3 2475.8 56.98 0.17 0.5 2475.8 56.98 0.19 0.7 2475.8 56.98 0.17 0.9 2475.8 56.98 0.18 1 1453.6 33.04 0.34 a -1 Standard uncertainties (u) are u(T) = 0.20 K, u(NaCl) = 1 mmol∙kg , u(UR) = 2 mmol∙kg-1, and

Jo

u(p) = 5 kPa (level of confidence = 0.68). Relative standard uncertainties (ur) are ur(V0) = ±3%, ur(lc) = ±3% and ur(P) = ±4%.

40

Journal Pre-proof Table 6. Aggregation number (Nagg) and other related parameters for AMHCl-BTC mixtures prepared in different solvent at temperature T = 298.15 K and pressure p = 0.1 MPa.a

ur

na

lP

re

-p

ro

of

α1 Nagg I1/I3 Ksv x 10-4 Dexp Dideal Aqueous system 0 22 1.57 1.54 45.23 0.1 31 1.50 7.21 39.17 40.01 0.3 40 1.39 1.10 30.45 38.47 0.5 47 1.39 0.88 30.62 37.94 0.7 58 1.44 0.78 34.44 37.76 0.9 71 1.45 0.61 35.19 37.52 1 50 1.45 0.58 35.51 50 mmol∙kg-1 NaCl 0 36 1.42 1.08 33.82 0.1 42 1.40 2.45 31.34 32.96 0.3 57 1.41 1.01 31.97 32.83 0.5 69 1.48 0.73 37.68 32.78 0.7 83 1.41 0.60 32.15 32.76 0.9 97 1.48 0.56 37.76 32.73 1 74 1.41 0.49 32.20 300 mmol∙kg-1 UR 0 20 1.58 1.62 46.04 0.1 26 1.47 5.85 37.38 40.04 0.3 33 1.35 1.48 27.64 38.21 0.5 41 1.42 2.66 32.95 37.57 0.7 49 1.44 2.14 34.94 37.32 0.9 59 1.45 1.78 35.51 37.03 1 39 1.44 0.69 34.69 a Standard uncertainties (u) are u(T) = 0.20 K, u(NaCl) = 1 mmol∙kg-1, u(UR) = 2 mmol∙kg-1 and

Jo

u(p) = 5 kPa (level of confidence = 0.68). Relative standard uncertainties (ur) are ur(Nagg) = ±4%, ur(I1/I3) = ±3%, ur(Ksv) = ±3% and u(Dexp/Dideal) = ±4%.

Author Statement Conceptualization: Malik Abdul Rub, Naved Azum Investigation: Malik Abdul Rub, Naved Azum, Abdullah M. Asiri Validation: Malik Abdul Rub, Abdulrahman Alabbasi, Naved Azum, Abdullah M. Asiri Formal analysis: Malik Abdul Rub, Naved Azum Methodology: Malik Abdul Rub, Abdulrahman Alabbasi, Naved Azum, Abdullah M. Asiri Project administration: Malik Abdul Rub, Naved Azum, Abdullah M. Asiri Visualization: Malik Abdul Rub, Naved Azum, Abdullah M. Asiri

41

Journal Pre-proof Supervision: Malik Abdul Rub, Abdullah M. Asiri Writing – original draft: Malik Abdul Rub, Naved Azum Writing – review & editing: Malik Abdul Rub, Abdulrahman Alabbasi, Naved Azum, Abdullah M. Asiri

Conflict of Interests

ro

of

The authors have declared that no competing interests exist.

-p

Research highlights

re

Aggregation of AMHCl and BTC surfactant mixtures have been investigated.

More value of

lP

Effect of NaCl and urea has been seen on the interaction of AMHCl and BTC. than

showing that the adsorption is more favorable.

negative.

na

Interaction parameter βm (bulk solution mixture) and βσ (mixed interface) were achieved

Jo

ur

Aggregation number (Nagg) and many other related parameters were also evaluated.

42