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Analysis of surface and bulk properties of amphiphilic drug ibuprofen and surfactant mixture in the absence and presence of electrolyte
Accepted Manuscript Title: Analysis of surface and bulk properties of amphiphilic drug ibuprofen and surfactant mixture in the absence and presence of electrolyte Author: Naved Azum Malik Abdul Rub Abdullah M. Asiri PII: DOI: Reference:
S0927-7765(14)00294-X http://dx.doi.org/doi:10.1016/j.colsurfb.2014.06.009 COLSUB 6455
To appear in:
Colloids and Surfaces B: Biointerfaces
Received date: Revised date: Accepted date:
21-5-2014 2-6-2014 3-6-2014
Please cite this article as: N. Azum, M.A. Rub, A.M. Asiri, Analysis of surface and bulk properties of amphiphilic drug ibuprofen and surfactant mixture in the absence and presence of electrolyte, Colloids and Surfaces B: Biointerfaces (2014), http://dx.doi.org/10.1016/j.colsurfb.2014.06.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
Analysis of surface and bulk properties of amphiphilic drug
2
ibuprofen and surfactant mixture in the absence and presence of
3
electrolyte
4
Naved Azum1, 2, *, Malik Abdul Rub1, 2, Abdullah M. Asiri1, 2
5
1
8
cr
us
2
Center of Excellence for Advanced Materials Research, King Abdulaziz University, P.O. Box
an
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Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia 21589
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80203, Jeddah, Saudi Arabia 21589
M
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te Ac ce p
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ip t
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*Corresponding author. Tel.: +966 126473648
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E-mail address: [email protected]
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1
ABSTRACT
3
In the present work, the micellization, adsorption and aggregation behavior of mixed drug-
4
surfactant systems, in the absence and presence of electrolyte (100 mM NaCl) were investigated
5
by surface tension and fluorescence measurements. The critical micelle concentrations (cmc) of
6
the mixtures fall between the values of the individual components, which indicate nonideal
7
behavior of mixing of the components. On the basis of regular solution theory (RST), the
8
micellar mole fractions of surfactant (X1) and interaction parameter in solution (β) were
9
evaluated, while their interfacial mole fractions (
an
us
cr
ip t
2
) and interaction parameters at the interface
(βσ) were calculated using Rosen’s model. The results indicate that the surfactant’s contribution
11
is greater than that of the drug both at the interface and in micelles. The short and rigid
12
hydrophobic structure of the drug resists its participation in micelle formation more than in the
13
monolayer, leading to X1 <
14
group (Amin) indicate attractive interactions. Γmax increases and Amin decreases as the surfactant
15
mole fraction increases. The results have applicability in model drug delivery.
16
Keywords: Mixed micelle, Ibuprofen, Interaction parameters, Aggregation number,
17
Micropolarity
d
te
. Values of the surface excess (Γmax) and minimum area per head
Ac ce p
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M
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1
1. Introduction The amphiphilic molecules (1-5) containing both hydrophobic and hydrophilic regions
3
are known to play a vital role in many processes of interest in both fundamental as well as
4
applied sciences. One important property of amphiphilic molecule is the formation of colloidal
5
sized aggregate in solution, known as micelles (1-5), which have particular significance in
6
pharmacy. The amphiphilic mixtures are mostly applied in cosmetics, detergency, enhanced oil
7
recovery and drug delivery, since they have improved characteristics compared to the single
8
amphiphilic solutions [6, 7]. In practical applications, reduction of the interfacial tension
9
ensuring amphiphile usefulness in a given process is very often demanded. In many cases it is
10
impossible to achieve proper reduction of the water surface tension by a single surfactant,
11
therefore, different king of amphiphilic mixtures are used.
M
an
us
cr
ip t
2
In recent years, much research has been directed toward the study of mixed amphiphilic
13
systems (e.g., surfactant-surfactant, surfactant-cosurfactant, surfactant-polymer, surfactant-
14
copolymer, surfactant-drug, drug-drug etc.) [8-15]. A mixed amphiphilic system can exhibit
15
surface and colloidal properties different from those of the pure individual components. Nonideal
16
mixing of amphiphilic components often causes synergism in the properties of the mixtures that
17
may be exploited in their applications. When a mixed amphiphile system shows lower critical
18
micelle concentration (cmc) values than that of pure components, the system is said to be
19
synergistic. As a result, mixed micelles are commonly used in pharmaceutical formulations, in
20
industries, and in enhanced oil recovery processes [16-18]. Conventional surfactants have cmc
21
values in milli moles and may disintegrate upon being diluted. In vivo, this may result in
22
precipitation of encapsulated drug causing a decrease in bioavailability and ability to penetrate
Ac ce p
te
d
12
3 Page 3 of 31
1
biological barriers [19]. This problem can be overpowered by the use of mixed micelles of drug
2
with different additives i.e., surfactants, biocompatible polymers, electrolytes etc. Ibuprofen (IBF), 2-(4-isobutylphenyl) propionic acid, is a well-known non-steroidal ant-
4
inflammatory drug (Scheme 1 (a)) commonly used to treat chronic pain and inflammation.
5
Unfortunately, oral consumption results in severe side effects, including gastrointestinal,
6
ulceration and some time bleeding. Moreover, IBF is a poorly water-soluble drug. However, the
7
sodium salt of ibuprofen used in the present study is easily soluble in aqueous solution.
8
Therefore, the development of a drug delivery system allowing the controlled release of IBF
9
would be useful, especially in high dose-dependent treatment, including chronic disease such as
10
rheumatoid arthritis. Oral route is the most convenient, economical, and frequently used route of
11
drug administration, but it suffers from a major drawback of poor gastrointestinal membrane
12
permeability. Penetration enhancers may be incorporated into various formulations in order to
13
overcome the problem of low permeability and bioavailability of drugs across the biological
14
membranes. They include surfactants, fatty acids, bile salts, medium chain glycerides, calcium
15
chelators such as ethylenediaminetetraacetic acid (EDTA), acyl carnitine and alkanoylchlolines
16
etc. Since surfactants are often used as penetration enhancers, so their mixture with amphiphilic
17
drug may improve their bioavailability.
Ac ce p
te
d
M
an
us
cr
ip t
3
18
Keeping the above in view and the fact that surfactant micelles, like many other
19
amphiphilic substances, are potentially important encapsulating / solubilizing agents, we have
20
performed
21
dodecylbenzenesulfonate) surfactant mixed systems in absence and presence of 100 mM NaCl.
22
As the electrolytes are found in the body and their concentration in the membranes may vary,
23
their presence and concentration may affect the micellization tendency of the drug and surfactant
tensiometric
and
spectrometric
measurements
on
IBF-SDBS
(Sodium
4 Page 4 of 31
as well as their mixed micelles. Therefore, it is important to have knowledge of drugs’
2
association behavior in presence of electrolytes. Clint, Rubingh, Motomura’s and Rosen’s
3
approaches have been utilized to obtain various parameters related to mixed micelles.
4
2. Materials and Experimentals
ip t
1
The anionic surfactant, SDBS and amphiphilic drug, IBF were the products of
6
Sigma with purity >98%. Pyrene, used as micellar probe in the fluorescence
7
measurements, was a Sigma product with purity >98%. A stock solution of pyrene was
8
prepared in absolute methanol. All solutions were prepared in double-distilled water of
9
specific conductivity: (10 to 50) μS cm-1 and experiments were done under thermostatic
an
us
cr
5
conditions at 298.15 K with accuracy of ±0.1 K.
11
2.1 Surface tension measurements
d
M
10
The cmc was determined by the surface tension () measurement. Sigma 700
13
(Attention) performed the experiments using a platinum ring, the ring detachment method
14
in a calibrated tension at a constant temperature of 298.15 K. Detailed procedure has been
15
reported earlier [20]. Each experiment was repeated at least three times.
16
2.2 Electronic absorption measurements
Ac ce p
te
12
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UV-visible spectroscopy investigations have been carried out to understand the
18
IBF-SDBS interactions. The absorbance spectra were recorded on an Evolution 300 UV-
19
vis spectrometer with a quartz cuvette.
20
5 Page 5 of 31
1
2.3 Fluorescence measurements The micellar aggregation number (Nagg) of single and mixed amphiphilic solutions
3
was determined by steady-state fluorescence quenching measurements. Pyrene was used
4
as a probe and cetylpyridinium chloride (CPC) as quencher throughout the study. The
5
steady-state fluorescence experiments were performed with a Hitachi F-7000
6
spectrofluorometer, connected to a PC. A 3 cm3 silica cell was used for the spectral
7
measurements at a constant temperature. By selecting 335 nm as the excitation
8
wavelength of the fluorescence probe (pyrene), the emission spectra of solution
9
components prepare in pyrene were recorded from 350 to 450 nm. The first and third
10
vibronic peaks of pyrene appear at 373 and 384 nm respectively (Fig. 1). At a constant
11
probe concentration of 1 × 10-6 M, the quencher concentration was varied from 0 to 1
12
×10-5 M to ensure a Poisson distribution for equilibration of solubilizates between
13
micelles.
15
cr
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an
M
d
te
Ac ce p
14
ip t
2
3. Results and discussion
16
The aqueous solubility of IBF more than 1500 mM was checked and is found to be freely
17
soluble in water. Figure 2 shows plots of surface tension versus [total amphiphile] in the absence
18
and presence of 100 mM NaCl. The cmc value of the pure IBF was found to be 180 mM in water
19
at 298.15 K, which agrees well with the previously reported value in the literature (179 mM)
20
[21]. The cmc values of pure SDBS also agree well with the literature (Table 1) [22]. As the
21
hydrophobic group of the drug (IBF) molecule is rigid, it is difficult for the drug molecules to
22
adjust in the curved area of a micelle. Therefore, the drug forms micelles, but at high 6 Page 6 of 31
concentrations, as compared to the surfactant (SDBS). The drug molecules will not choose the
2
sites between the head groups due to electrostatic repulsion, but they can still choose the second
3
site around the exterior surface of anionic micelles, i.e., between the stern layer and shear
4
surface. The IBF ions residing outside the stern layer may now be considered to form ion-pairs
5
with the sodium counterions present in the stern layer. This is schematically; shown in Scheme 1
6
(b).This fashion of adsorption of drug molecules reduces magnitude of work for micellization
7
thus decreasing cmc. In the presence of NaCl (Fig. 2 (b)), the cmc of IBF was lowered, whereas
8
no significance change was observed for cmc of SDBS. The cmc of mixed systems of a particular
9
composition decreases further on adding inorganic salt (100 mM NaCl). The depression of cmc
10
in the presence of electrolytes is due to screening effect of the salt (the thickness of the electric
11
double layer surrounding the ionic head groups and consequent decrease electrical repulsion
12
between them in the micelle). The cmc values of the mixed systems usually fall in between the
13
values of pure components in the presence and absence of salt (100 mM NaCl). This means that
14
the mixed micelles are formed due to attractive interactions between the two components.
15
Results presented in Table 1, clearly indicate that the large decrease in cmc of drug + surfactant
16
is in the presence of NaCl.
cr
us
an
M
d
te
Ac ce p
17
ip t
1
For ideal mixtures, cmc of mixed systems can be predicted using Clint’s model [23,24]:
18
1 i cmcideal cmci
19
where αi and cmci are the stoichiometric mole fraction and cmc of ith component under the
20
similar experimental conditions. For the binary drug–surfactant systems, the equation becomes
21
1 1 2 cmcideal cmc1 cmc2
(1)
(2)
7 Page 7 of 31
cmc1 and cmc2 are the cmc of the pure surfactant (SDBS) and drug (IBF), respectively, and α1
2
and α2 are their mole fractions. The theory is over simplication and idealization, which considers
3
that the individual components are non-interacting, and their individual cmc values reflect their
4
relative tendency towards mixed micellization. Any deviation from cmcideal would, however,
5
account for interactions among amphiphiles. Divergence in positive and negative sides indicates
6
antagonism and synergism, respectively, in the system. In these systems, the cmc values come
7
out to be lower than cmcideal values– this indicates that the drug–surfactant mixed micelles are
8
formed by attractive interactions between the IBF and anionic SDBS, which is also an indication
9
of nonideal behavior of mixing. Therefore due to attractive interaction between the components
10
(IBF and SDBS) cmcid values comes out to be more than experimental cmc values. The cmc
11
values have been used to determine the composition of the mixed micelles and the micellar
12
molecular interaction parameter (β) among the components by applying the phenomenological
13
models given by Rubingh [25]. The fundamental equations of Rubingh’s model are:
14
[ln (cmcexp 1 / cmc1 X 1 )] /(1 X 1 ) 2
15
Where X1
cr
us
an
M
d
te
(3)
Ac ce p
16
ip t
1
(4)
17
X1 is micellar mole fraction of surfactant (component 1). The X1 values for mixed systems
18
increase with increase in surfactant concentration (Table 1). With the increase in concentration of
19
surfactant in the solution, contributions of surfactants in the mixed micelles also increase. In all
20
systems, X1 is always greater than α1. As the micelle mole fraction of surfactant in the solutions
21
is very small, the micelles in the ideal state should contain less surfactant. It seems that the added 8 Page 8 of 31
1
surfactant replaces some of the drug molecules from the mixed micelles resulting in some
2
reduction in steric hindrance in the micellar core. Hence, more surfactant is present in mixed
3
micelles as compared to the ideal state. All the results and discussion given above indicate synergistic interactions between the
5
two components of the mixed micelles. As such, the interaction parameter, β, comes out to be
6
negative at all mole fractions. The values are greater in the presence of NaCl, which are in line
7
with the X1 values. On adding the NaCl, the attractive interaction between two amphiphiles
8
increases. For the mixture of like charged ionic amphiphiles, the contributions to the interaction
9
between the amphiphiles are from Van der Waals interaction between the tails of the amphiphiles
10
and the repulsive interaction between the head groups. The interaction between the tails is
11
negative and that between the heads is positive. With the addition of NaCl, the repulsive
12
interaction between the like charged head groups decreases because of high ionic strength in the
13
solution, which in turn makes β becoming more negative. The β becoming more negative due to
14
addition of NaCl to the present mixed system is similar to the reported earlier [26,27].
16 17 18
cr
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an
M
d
te
The values of β are used to calculate the activity coefficients of the components using the
Ac ce p
15
ip t
4
following equations:
(5) (6)
19
From Eqs. (5) and (6), the β and X1 values are used for evaluating f1 and f2. The values of activity
20
coefficients for systems are less than unity (Table 1) indicating non-ideal behavior for mixed
21
micelles.
9 Page 9 of 31
Motomura and Aratono [28] developed a model that is an attempt to overcome the
2
limitations of Rubingh’s regular solution theory and improved the predictions of phase
3
separation model. Basically, it is a thermodynamic method that considers mixed micelles as a
4
macroscopic bulk phase where the energetic parameters of such systems can be evaluated in
5
terms of excess thermodynamic quantities. In the present study, only the micellar mole fraction
6
of mixed systems in the ideal state (X1id) has been computed using Motomura’s approximation as
7
follows:
8
X1
9
It is evident from the Table 1 that X1 values are less than X1id for all the mole fractions, indicating
10
that the mixed micelles formed by these systems contain more contribution of IBF than in its
11
ideal mixing state.
12
3.1 Interfacial phenomenon
us
(7)
M
an
1cmc2 1cmc2 2 cmc1
te
d
id
cr
ip t
1
Amphiphiles orient at the air/water interface and decrease the surface tension. The
14
physical properties of the interface can be very important in all types of natural phenomena and
15
industrial processing operations. Many industrial processes involve colloidal dispersions, such as
16
foam, emulsions and suspensions, all of which contain large interfacial areas and hence the
17
properties of these interfaces may also play a large role in determining the properties of the
18
dispersions themselves. On the basis of adsorption isotherm, maximum surface excess
19
concentration at air/water interface, Γmax can be calculated by using the Gibbs adsorption
20
equation in the following form [27]:
Ac ce p
13
(8)
21
10 Page 10 of 31
Where (d/dlog S) is the maximum slope, is the surface tension of the solution. R and T are the
2
gas constant and absolute temperature, respectively. n is introduced to allow simultaneous
3
adsorption of cation and anion. The value of n is used as 2; but in the presence of NaCl an
4
excess amount of Na+ in 100 mM NaCl, n = 1[29]. The higher the Γmax, steeper is the approach to
5
cmc and higher the surface activity. Γmax increases with the addition of NaCl (Table 2) which is a
6
general trend observed in single amphiphile solutions and such a variation in Γmax is attributed to
7
the salting-out effect of the added electrolyte. Moreover, counterion binds to the adsorption layer
8
and reduces the repulsive interaction between the head groups of the adsorbed ionic amphiphiles
9
causing enhancement of adsorption or increase of Γmax. The Γmax values were further used to
10
evaluate the minimum area per surfactant molecule, Amin at the air/water interface using the
11
following equation
M
an
us
cr
ip t
1
(9)
te
d
12
NA in this equation is the Avogadro number. These values suggest whether the amphiphile is
14
closely packed of loosely packed at air/water interface. The Amin values are lower in mixed
15
amphiphile system than the pure components. The low Amin values suggest that the amphiphiles
16
are closely packed so their orientation is almost perpendicular to the interface. In the presence of
17
NaCl, the Amin values for mixed system are higher than the SDBS but lower than IBF.
18
Ac ce p
13
The interfacial composition ( X1 ) and interaction parameter (βσ) can be evaluated using
19
Rosen’s model [30], analogous to Rubingh’s model for mixed micelles, as:
20
[ln (Cmix 1 / C1 X 1 )] /(1 X 1 ) 2
(10)
(11)
21 11
Page 11 of 31
is the monolayer mole fraction of SDBS in the mixture, C1 , C 2 and Cmix are the
1
Where
2
molar concentrations in the solution phases of mixture, component 1 and component 2,
3
respectively, at a particular mole fraction of component 1 required to produce a given value.
4
Values of
5
surfactant than the mixed micelles. Due to the rigid ring system of the drug molecules prefer the
6
monolayer and, therefore, less surfactant is present in the monolayer. In the absence of
7
electrolyte, the average βσ values are greater than β.
8
3.2 Thermodynamic parameters
ip t
cr
us
an
10
The standard free energy of micellization (
) is calculated in accordance with the
pseudophase model using the following equation [31]
M
9
are lower than X1 values indicating that the mixed monolayer contains less
d
11
(12)
Where Xcmc, is the cmc of the mixture in mole fraction unit. The
13
all the binary systems have considerable spontaneity of micellization. The standard Gibbs energy
14
of adsorption,
Ac ce p
15
values (Table 2) reveal that
te
12
, is related to Gibbs energy of micellization through relation[32,33]: (13)
16
where Π cmc is the surface pressure at the cmc and is equal to (0 − cmc) where 0 is the surface
17
tension of pure solvent and cmc is that of the solution at the cmc. The values of
18
are all negative and greater than
19
adsorb at the interface and then form mixed micelles. The values of pure components are less
20
negative than those of the mixtures, indicating that the mixed systems are more active than those
21
of the pure components.
(Table 2)
(in magnitude). This shows that amphiphiles first try to
12 Page 12 of 31
The molar Gibbs energy at the maximum adsorption attained at cmc, Gmin, is given by
1 2
[34]: (14)
ip t
3
It is the minimum Gibbs energy of the given surface with fully adsorbed amphiphile molecules.
5
The lower the value of the Gibbs energy the more thermodynamically stable is the surface
6
formed.
us
cr
4
The excess free energy of micellization, ∆Gex, can be calculated by the equation
an
7 8
(15)
The negative values suggest that the mixed micelles are more stable than the micelles of
10
pure amphiphiles. Mixed micelles have fairly different physicochemical properties from those of
11
pure micelles of individual components. From the application point of view, mixed micelles are
12
of great importance in biological, technological, pharmaceutical and medicinal formulation,
13
enhanced oil recovery process for the purpose of solubilization, suspension, dispersion, etc. It
14
was found that the cmc of mixed amphiphiles was lower than either of the individual
15
amphiphiles which is greatly valuable because it decreases the total amount of amphiphile used
16
in meticulous purpose leading in lessening of cost and environmental affect. Therefore micelle
17
formed by mixing of two components is more stable in contrast to micelle form by single
18
component. Micelles formed in the electrolyte solution are more stable shown by results (Table
19
2).
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d
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20 21
13 Page 13 of 31
1
3.3 Micro-environment and aggregation number Fluorescence spectroscopy has been successfully used for the study of central issues of
3
solutions of amphiphiles. Different techniques and methods are uniquely adapted to investigate
4
problems in this field. The extrinsic and intrinsic probes can be used, to provide information on
5
molecular association, microstructure and molecular dynamics. This constitutes an important
6
contribution to the understanding and control of microscopic properties, as well as to their
7
biological functions and technical applications. One of the most popular fluorescent probes is
8
pyrene. Its emission spectrum depends strongly on the solvent in such a way that the relative
9
intensity of I and III bands has been empirically related to environment polarity, and, therefore,
10
gives specific information on the absence or presence of micelles or other hydrophobic domains.
an
us
cr
ip t
2
The quenching of fluorescence probe will depend on its confinement in a micro domain,
12
such as a micelle or a micro emulsion droplet. From the fluorescence decay parameters the
13
concentration of micro domains can be obtained and from this the aggregation numbers can be
14
determined. In the general case of a micellar solution containing low concentrations of a
15
luminescence probe and of a quencher, there are empty micelles with either luminescent probe or
16
quencher, and micelles with both probe and quencher. The luminescence intensity can, under
17
certain conditions, be assumed proportional to the concentration of probe molecules in micelles,
18
which contain no quencher. For the simplest case, where the micelles are small and mono
19
disperses, the determination of aggregation numbers is straightforward. The probe and quencher
20
distribution are assumed stationary, following a poisson distribution.
Ac ce p
te
d
M
11
21
If a micellar solution contains an unknown micelle concentration [M] and a quencher of
22
concentration [Q], adding a luminescent probe, pyrene, to the micellar system will enable it to
23
partition both among micelles with quencher and with empty micelles. If probe molecule is
14 Page 14 of 31
1
luminescent only when it occupies an empty micelle, then the measured ratio of intensities in
2
presence (I) and absence (Io) of quencher is related as [35,36]
3
I ln Io
4
[M] can be written as
5
[M]
6
where [S]T is the total concentration of surfactant mixture, Nagg is the micellar aggregation
7
number.
8
Combining Eqs. (16) and (17) leads to
9
N agg [Q] I ln o I [S]T cmc
[Q ] [M ]
cr
ip t
(16)
(17)
(18)
d
M
an
us
[S]T cmc N agg
Eq. (18) predicts a linear plot between ln(Io/I) and [Q] with a slope equal to Nagg/([S]T)-cmc),
11
which gives the values of Nagg (Fig. 3). Aggregation number of ionic amphiphiles is reported to
12
increases in the presence of NaCl (Table 3). The added electrolyte tend to decrease the area per
13
amphiphile molecule by better screening of electrostatic repulsion between the ionic heads as a
14
result of increase in the number of counter ions in the Stern diffuse layers.
Ac ce p
te
10
15
The above results can further be explained on the basis of quenching. The strength of
16
hydrophobic environment can be evaluated by determining the first order quenching rate
17
constant, the so called Stern-Volmer binding constant (Ksv) [37], using the relation:
18
Io 1 K sv [Q] I
(19)
15 Page 15 of 31
Ksv gives an idea about bimolecular quenching and unimolecular decay as it being the product of
2
rate constant of the quenching process and lifetime of the probe in the absence of bimolecular
3
quenching [38]. Greater the solubility of the probe and quencher, higher would be the Ksv value.
4
High Ksv values (presented in Table 3) suggest an increase in quenching due to presence of both
5
pyrene and quencher in strong hydrophobic environment.
ip t
1
The results are further explained on the basis of micropolarity of the microenvironment
7
of mixed micelles over the whole mixing range. The I1/I3 ratio is directly related to the
8
environment in which pyrene is solubilized and senses the degree of hydrophobicity of that
9
environment. The ratio of intensity of the first and third vibronic peaks, i.e., I1/I3, of the pyrene
10
fluorescence emission spectrum in the presence of surfactant is considered the index of
11
micropolarity of the system. A value less than 1 generally indicates that pyrene is in the non-
12
polar environment while values greater than 1 mean pyrene having a polar surrounding [38].
13
Characteristic values of I1/I3 of pyrene in some solvents are 0.6 in cyclohexane; 1.04 in toluene;
14
1.23 in ethanol; 1.33 in methanol and 1.84 in water [38]. The average values of I1/I3 ratio at
15
different quencher concentrations are also given in Table 3. These values are close to the I1/I3
16
ratio for methanol and ethanol.
us
an
M
d
te
Ac ce p
17
cr
6
The apparent dielectric constant (D) of the medium can be estimated by the relation [37]:
18
I1 1.00461 0.01253D I3
19
The values given in Table 3 show that there is no definite trend in D values. These values are
20
close to the D values for methanol and ethanol [39], again confirming that the solubilized pyrene
21
is in a short alcohol-like environment. The ideal dielectric constant inside the mixed micelle can
22
be computed from the following relation:
(20)
16 Page 16 of 31
(21)
1
It is clear from Table 3 that the experimental values are somewhat different from the calculated
3
values. This is because IBF has some attractive interactions inside the micelle.
4
3.4 Effects of IBF concentration on the UV-vis absorption spectra of SDBS
ip t
2
The absorption spectra of SDBS+IBF in the presence and absence of NaCl are presented
6
in Fig 4. The pure SDBS exhibits two absorbtion band at 260 and 230 with or without
7
electrolyte. On the addition of IBF, the absorption of monomer band increases. The increase in
8
absorption with increase IBF concentration is due to the interaction of SDBS with IBF.
us
cr
5
10
an
9
4. Conclusion
The interfacial and micellar behavior in the mixture of SDBS and IBF amphiphile
12
systems in the absence and presence of electrolyte (100 mM NaCl) were studied. We observed
13
that, in the absence of electrolyte the attractive interaction in the mixed micelle is lower than that
14
in mixed monolayer at the air/water interface. However, the β, βσ values are negative, which
15
indicates that there is synergistic interaction in both micellar and monolayer states and in the
16
absence and presence of an electrolyte. This study has confirmed that the synergism in mixed
17
micelle formation can be enhanced by adding salt. The negative values of
18
mixed micelles are more stable than the micelles of pure amphiphiles. Micelles formed in the
19
electrolyte solution are more stable. The Nagg values of mixed surfactant system are lower than
20
SDBS. The degree of negative deviation in I1/I3 values increases with NaCl in comparison to
21
their absence. The value of Ksv of mixture increases with NaCl. The experimentally determine
22
and calculated apparent dielectric constants for our systems are lower than that of ideal one
23
because of attractive interaction inside the micelle.
Ac ce p
te
d
M
11
suggest that the
17 Page 17 of 31
1
3 4
Acknowledgments Chemistry Department and Centre of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah are highly acknowledged.
ip t
2
cr
5
us
6
an
7 8
M
9
13 14 15
te
12
Ac ce p
11
d
10
16 17 18
18 Page 18 of 31
1
3
References [1]
C. Tanford, The Hydrophobic Effect: Formation of Micelles &Biological
ip t
2
Membranes; Wiley Publishing, New York, 1980.
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[2]
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cr
5
M.S. Alam, D. Samanta, A. B. Mandal, Colloids Surf. B: Biointerfaces 92 (2012) 203– 208.
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[5]
M.S. Alam, A. B. Mandal, J. Molecular Liquids 168 (2012) 75-79.
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M.J. Rosen, in: Scamehorn, J.F. (Ed.), Phenomena in Mixed Surfactant Systems, ACS
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Symposium series 311, American Chemical Society, Washington, DC, 1989.
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R. Zana, H. Levy, K. Kwetkat, Colloid Interface Sci. 197 (1998) 370-376.
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N. Azum, M. A. Rub, A. M. Asiri, A.A.P. Khan, A. Khan, S.B. Khan, M.M. Rahman, A.O. Al-Youbi, J. Sol. Chem. 42 (2013) 1532-1544.
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R.G. Alargova, I.I. Kochijashky, M.L. Sierra, K. Kwetkat, R. Zana, J. Colloid Interface Sci. 235 (2001) 119-129.
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ud-Din, J. Chem. Thermodynamics 64 (2013) 28-39
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P. M. Holland, in: P.M. Holland, D.N. Rubingh (Eds.), Mixed Surfactant Systems, ACS Symposium Series, American Chemical Society, Washington, D.C., 1992.
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ip t
Kabir-ud-Din , J. Indus. Eng. Chem.19 (2013) 1774-1780.
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M.A. Rub, A.M. Asiri, N. Azum, A. Khan, A.A.P. Khan, S.B. Khan, M.M. Rehman,
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M.A. Rub, M.S. Sheikh, A.M. Asiri, N. Azum, A. Khan, A.A.P. Khan, S.B. Khan, Kabir-
R. M. Hill, in: K. Ogino, M. Abe (Eds.), Mixed Surfactant Systems, Surfactant Science Series, vol. 46, Dekker, New York, 1993.
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V. P. Torchilin, J. Control Release 73 (2001) 137-172.
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L.D. Song, M.J. Rosen, Langmuir 12 (1996) 1149-1153.
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A. Ridell, H. Evertsson, S. Nilsson, L.O. Sundelöf, J. Pharm. Sci. 88 (1999)1175-1181.
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A. Fachini, I. Joekes, Colloids Surfaces A 201 (2002) 151–160.
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J.H. Clint, J. Chem. Soc. Faraday Trans. 171 (1975) 1327-1334.
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[24]
J.H. Clint, Surfactant Aggregation, Chapman and Hall, New York, 1992.
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[25]
D.N. Rubingh, Solution Chemistry of Surfactants, Plenum, New York, 1979.
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[26]
K. Motomura, M. Aratono, Mixed Surfactant Systems, Dekker, New York, 1998.
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E. Junquera, E. Aicart, Langmuir 18 (2002) 9250–9258.
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A.A. Dar, G.M. Rather, A.R. Das, J. Phys. Chem. B111 (2007) 3122–3132.
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K. Motomura, M. Aratono, in: K. Ogino, M. Abe (Eds.), Mixed Surfactant Systems,
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te
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Marcel Dekker, New York, 1993.
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an
9
[30]
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[31]
2004.
2 3
M.J. Rosen, Surfactants and Interfacial Phenomena, John Wiley & Sons, New York,
[32]
K. Tsubone, K.Y. Arakawa, M.J. Rosen, J. Colloid Interface Science 262 (2003) 516524.
4
ip t
1
[33]
M.J. Rosen, S. Aronson, Colloid Surf. 3 (1981) 201-208.
6
[34]
G. Sugihara, A.M. Miyazona, S. Nagadome, T. Oida, Y. Hayashi, J.S. Ko , J Oleo Sci. 52
cr
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us
( 2001) 449-456.
7
[35]
N.J. Turro, A. Yekta, J. Am. Chem. Soc., 100 (1978) 5951-5952.
9
[36]
N. Azum, M.A. Rub, A.M. Asiri, J. Dispersion Science and Technology 35 (2014) 358363.
[37]
K.K. Rohatgi-Mukherjee, Fundamentals of Photochemistry, Wiley Eastern, New Delhi,
M
10 11
an
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1992.
12
[38]
K. Kalyanasundram, J.K. Thomas, J. Am. Chem. Soc. 99 (1977) 2039-2044.
14
[39]
N.J. Turro, P.L. Kuo, P. Somasundaran, K. Wong, J. Physical Chem. 90 (1986) 288-29.
16 17 18 19
te
Ac ce p
15
d
13
20 21 22 23
21 Page 21 of 31
1 2
Caption
4
Table 1. Various physicochemical properties of SDBS+IBF mixed amphiphilic systems.
5
Table 2. Various interfacial properties and energetic parameters of SDBS and IBF mixed
6
amphiphilic system.
7
Table 3. Aggregation number (Nagg), Stern-Volmer binding constant (Ksv), micropolarity (I1/I3),
8
and apparent dielectric constant (D) for SDBS and IBF mixed amphiphilic systems.
9
Scheme 1. Schematic diagram showing (a) chemical structure of Ibuprofen (IBF), (b) ion pair
an
us
cr
ip t
3
interaction between SDBS micelle and IBF.
11
Fig. 1. Representative fluorescence (emission) spectra of 10−6 M pyrene in 100 mM NaCl
12
solution of SDBS + IBF (4:6) at different quencher concentrations (maximum intensity indicates
13
no quencher and minimum intensity indicates maximum amount of quencher).
14
Fig. 2. Plots showing variation of surface tension () with log [S] at 298 K (a) in absence of salt
15
(b) in presence of 100 mM NaCl (c) pure IBF.
16
Fig. 3. Plots for determination of aggregation number (Nagg) of SDBD + IBF mixed systems in
17
100 mM NaCl solution.
18
Fig. 4. Absorption spectra of SDBS in presence of different concentration of IBF (A) with NaCl
19
(B) without NaCl.
Ac ce p
te
d
M
10
20 21 22 23 22 Page 22 of 31
1 2
Table 1. αSDBS
cmcid (mM)
cmcexp (mM)
β
X1
Xideal
f1
-3.28
0.825
0.975
-2.79
0.913
-2.97
0.947
-3.71
0.976
0.6 0.8 1.0
5.61
4.29
2.85
2.57
1.91
1.80
1.44
1.40 1.15 [1.59]
b
1.15
0.6 0.8
1.0
5 6 7 8
0.257 0.204 0.195
1.13
2.84 1.91 1.43
0.990
0.979
0.097
0.995
0.991
0.069
0.998
0.997
0.029
-13.26
0.616
0.971
0.141
0.006
-14.71
0.635
0.989
0.140
0.002
-15.26
0.655
0.995
0.162
0.001
-15.63
0.679
0.998
0.199
0.001
1.13
The uncertainty limits of cmc is ±2%. a
Ac ce p
4
0.501
159 5.59
d
0.4
159
te
0.0 0.2
0.107
M
SDBS + IBF + 100 mM NaCl
0.904
us
0.4
180
180 [179]a
an
0.2
cr
SDBS + IBF 0.0
f2
ip t
3
Literature value [21]
b
Literature value [22]
9 10 11
23 Page 23 of 31
1 2
Table 2. Cσideal (mM)
Xσ
βσ
107 Γmax (mol m–1)
Amin (nm2 molecule–1)
П
Gm (kJ mol-1)
SDBS + IBF 0
2.61
2.61
Gad (kJ mol-1)
Gmin (kJ mol-1)
ip t
Cσmix (mM)
αSDBS
cr
3
Gex (kJ mol-1)
11.19
1.48
38.26
-41.80
-45.22
0.283
–
22.87
0.72
39.26
-45.92
-47.63
0.134
-1.174
0.496
0.589
0.4
0.408
0.332
0.006
-8.76
26.10
0.63
37.91
-46.40
-47.85
0.123
-0.549
0.6
0.267
0.231
0.162
-4.29
22.59
0.73
37.42
-47.45
-49.10
0.144
-0.369
0.8
0.199
0.177
0.515
-2.84
26.72
0.62
37.42
-48.18
-49.58
0.122
-0.215
1
0.14
0.144
13.12
1.26
37
-48.99
-51.81
0.251
0
17.00
17
40.29
-37.16
-39.83
0.197
42.34
-49.23
-50.56
0.086
-7.773
0.43
42.59
-44.80
-45.91
0.072
-8.450
0.45
0.130
0.4
0.78
0.780
0.001
0.6
0.56
0.56
0.8
0.44
0.44
1
0.41
0.41
6
0.135
-.37
36.44
0.617
-4.72
28.20 44.34
te
5
38.10
an
-45.61
-46.78
0.075
-8.547
42.39
-46.21
-47.72
0.097
-8.440
0.37
42.14
-46.39
-47.34
0.062
Table 3.
105Ksv
I1/I3
Dexp
Dideal
0.03 1.59 0.84 0.81 1.07 1.63
1.26 1.62 1.33 1.28 1.13 1.27
21 49 26 22 10 19
21 19 19 19 19 19
SDBS + IBF + 100 mM NaCl 0.0 88 1.38 1.23 0.2 115 1.64 1.12 0.4 117 0.67 1.11 0.6 139 0.99 1.09 0.8 175 1.74 1.24 1.0 205 0.76 1.09
19 09 08 07 18 07
19 12 11 11 11 07
α1 Nagg SDBS + IBF 0.0 57 0.2 31 0.4 76 0.6 86 0.8 120 1.0 140
7
42.39
0.58
The uncertainty limits of ∆Gm, ΔGad, Gmin, and Gex ±3%, ±4%, ±4% and ±4%, respectively.
Ac ce p
4
-4.85
M
0.13
d
0.2
–
SDBS + IBF + 100 mM NaCl 15.11 1.09 – 31.95 0.51
us
0.2
–
The uncertainty limits of Nagg is ±3%. 24 Page 24 of 31
1
M
an
us
cr
ip t
2
– + – +
–
+
Ac ce p
+
te
d
(a)
–
–
O
O
+ –
–
–
+
–
+
+
SDBS micelle
Ibuprofen
(b) 3
25 Page 25 of 31
1
Scheme 1.
2
ip t
3
us
cr
4
2500
an
Intensity
2000
1500
500
0 360
380
M
1000
400
420
440
5 6 7
Fig. 1.
Ac ce p
te
d
wavelength (nm)
26 Page 26 of 31
70
SDBS= 0.2 SDBS= 0.4
65
SDBS= 0.6
60
SDBS= 0.8
50 45
cr
/ mNm
-1
ip t
55
40
30 -4.0
-3.6
-3.2
-2.8
-2.4
-2.0
an
log [S] (M)
us
35
M
(A)
SDBS= 0.4 SDBS= 0.6 SDBS= 0.8
te
35
Ac ce p
/ mNm
-1
45
40
SDBS= 0.2
d
50
30
25
-4.8
-4.4
-4.0
-3.6
-3.2
log [S] (M)
(B)
27 Page 27 of 31
60
without NaCl with NaCl
55
ip t
45
40
cr
/ mNm
-1
50
30 -1.8
-1.6
-1.4
-1.2
-1.0
(C)
Fig. 2.
-0.6
-0.4
M
1
-0.8
an
log [IBF] (M)
us
35
12
te
d
2
SDBS= 0.2
Ac ce p
SDBS= 0.4
10
SDBS= 0.6 SDBS= 0.8
ln I0 / I1
8
6
4
2
0 0.00000
0.00002
0.00004
0.00006
0.00008
[CPC] (M)
3 4
Fig. 3.
28 Page 28 of 31
5
ip t
3
1
0
200
cr
2
[IBF](mM) 0 20 40 80 120 160 180 200 220
240
260
280
(A)
M
2
7
d
6
te
4 3
Ac ce p
Absorbance
5
300
an
Wavelength(nm)
1
us
Absorbance
4
[IBF](mM) 0 20 40 80 120 160 180 200
2 1 0
200
3 4 5
220
240
260
280
300
Wavelength(nm)
(B)
Fig. 4.
6
29 Page 29 of 31
Research Highlights
2 3
1. Mixed micelles formed in the presence of electrolyte are more stable in comparison to its absence.
4
2. The synergism in mixed micelle formation can be enhanced by adding salt.
5
3. Ibuprofen form ion-pairs with the sodium counterions of the surfactant.
ip t
1
Ac ce p
te
d
M
an
us
cr
6
30 Page 30 of 31
1 2
Graphical Abstract
3
–
+
–
–
– +
–
–
+ +
+
–
+
M
–
–
an
+
SDBS micelle
8 9 10
te
7
Schematic diagram showing ion pair interaction between SDBS micelle and IBF.
Ac ce p
6
Ibuprofen
d
5
O
us
+
cr
O
ip t
4
31 Page 31 of 31
S0927-7765(14)00294-X http://dx.doi.org/doi:10.1016/j.colsurfb.2014.06.009 COLSUB 6455
To appear in:
Colloids and Surfaces B: Biointerfaces
Received date: Revised date: Accepted date:
21-5-2014 2-6-2014 3-6-2014
Please cite this article as: N. Azum, M.A. Rub, A.M. Asiri, Analysis of surface and bulk properties of amphiphilic drug ibuprofen and surfactant mixture in the absence and presence of electrolyte, Colloids and Surfaces B: Biointerfaces (2014), http://dx.doi.org/10.1016/j.colsurfb.2014.06.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
Analysis of surface and bulk properties of amphiphilic drug
2
ibuprofen and surfactant mixture in the absence and presence of
3
electrolyte
4
Naved Azum1, 2, *, Malik Abdul Rub1, 2, Abdullah M. Asiri1, 2
5
1
8
cr
us
2
Center of Excellence for Advanced Materials Research, King Abdulaziz University, P.O. Box
an
7
Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia 21589
6
80203, Jeddah, Saudi Arabia 21589
M
9
13 14
te Ac ce p
12
d
10 11
ip t
1
15
*Corresponding author. Tel.: +966 126473648
16
E-mail address: [email protected]
17 18 19 1 Page 1 of 31
1
ABSTRACT
3
In the present work, the micellization, adsorption and aggregation behavior of mixed drug-
4
surfactant systems, in the absence and presence of electrolyte (100 mM NaCl) were investigated
5
by surface tension and fluorescence measurements. The critical micelle concentrations (cmc) of
6
the mixtures fall between the values of the individual components, which indicate nonideal
7
behavior of mixing of the components. On the basis of regular solution theory (RST), the
8
micellar mole fractions of surfactant (X1) and interaction parameter in solution (β) were
9
evaluated, while their interfacial mole fractions (
an
us
cr
ip t
2
) and interaction parameters at the interface
(βσ) were calculated using Rosen’s model. The results indicate that the surfactant’s contribution
11
is greater than that of the drug both at the interface and in micelles. The short and rigid
12
hydrophobic structure of the drug resists its participation in micelle formation more than in the
13
monolayer, leading to X1 <
14
group (Amin) indicate attractive interactions. Γmax increases and Amin decreases as the surfactant
15
mole fraction increases. The results have applicability in model drug delivery.
16
Keywords: Mixed micelle, Ibuprofen, Interaction parameters, Aggregation number,
17
Micropolarity
d
te
. Values of the surface excess (Γmax) and minimum area per head
Ac ce p
18
M
10
19 20 21 2 Page 2 of 31
1
1. Introduction The amphiphilic molecules (1-5) containing both hydrophobic and hydrophilic regions
3
are known to play a vital role in many processes of interest in both fundamental as well as
4
applied sciences. One important property of amphiphilic molecule is the formation of colloidal
5
sized aggregate in solution, known as micelles (1-5), which have particular significance in
6
pharmacy. The amphiphilic mixtures are mostly applied in cosmetics, detergency, enhanced oil
7
recovery and drug delivery, since they have improved characteristics compared to the single
8
amphiphilic solutions [6, 7]. In practical applications, reduction of the interfacial tension
9
ensuring amphiphile usefulness in a given process is very often demanded. In many cases it is
10
impossible to achieve proper reduction of the water surface tension by a single surfactant,
11
therefore, different king of amphiphilic mixtures are used.
M
an
us
cr
ip t
2
In recent years, much research has been directed toward the study of mixed amphiphilic
13
systems (e.g., surfactant-surfactant, surfactant-cosurfactant, surfactant-polymer, surfactant-
14
copolymer, surfactant-drug, drug-drug etc.) [8-15]. A mixed amphiphilic system can exhibit
15
surface and colloidal properties different from those of the pure individual components. Nonideal
16
mixing of amphiphilic components often causes synergism in the properties of the mixtures that
17
may be exploited in their applications. When a mixed amphiphile system shows lower critical
18
micelle concentration (cmc) values than that of pure components, the system is said to be
19
synergistic. As a result, mixed micelles are commonly used in pharmaceutical formulations, in
20
industries, and in enhanced oil recovery processes [16-18]. Conventional surfactants have cmc
21
values in milli moles and may disintegrate upon being diluted. In vivo, this may result in
22
precipitation of encapsulated drug causing a decrease in bioavailability and ability to penetrate
Ac ce p
te
d
12
3 Page 3 of 31
1
biological barriers [19]. This problem can be overpowered by the use of mixed micelles of drug
2
with different additives i.e., surfactants, biocompatible polymers, electrolytes etc. Ibuprofen (IBF), 2-(4-isobutylphenyl) propionic acid, is a well-known non-steroidal ant-
4
inflammatory drug (Scheme 1 (a)) commonly used to treat chronic pain and inflammation.
5
Unfortunately, oral consumption results in severe side effects, including gastrointestinal,
6
ulceration and some time bleeding. Moreover, IBF is a poorly water-soluble drug. However, the
7
sodium salt of ibuprofen used in the present study is easily soluble in aqueous solution.
8
Therefore, the development of a drug delivery system allowing the controlled release of IBF
9
would be useful, especially in high dose-dependent treatment, including chronic disease such as
10
rheumatoid arthritis. Oral route is the most convenient, economical, and frequently used route of
11
drug administration, but it suffers from a major drawback of poor gastrointestinal membrane
12
permeability. Penetration enhancers may be incorporated into various formulations in order to
13
overcome the problem of low permeability and bioavailability of drugs across the biological
14
membranes. They include surfactants, fatty acids, bile salts, medium chain glycerides, calcium
15
chelators such as ethylenediaminetetraacetic acid (EDTA), acyl carnitine and alkanoylchlolines
16
etc. Since surfactants are often used as penetration enhancers, so their mixture with amphiphilic
17
drug may improve their bioavailability.
Ac ce p
te
d
M
an
us
cr
ip t
3
18
Keeping the above in view and the fact that surfactant micelles, like many other
19
amphiphilic substances, are potentially important encapsulating / solubilizing agents, we have
20
performed
21
dodecylbenzenesulfonate) surfactant mixed systems in absence and presence of 100 mM NaCl.
22
As the electrolytes are found in the body and their concentration in the membranes may vary,
23
their presence and concentration may affect the micellization tendency of the drug and surfactant
tensiometric
and
spectrometric
measurements
on
IBF-SDBS
(Sodium
4 Page 4 of 31
as well as their mixed micelles. Therefore, it is important to have knowledge of drugs’
2
association behavior in presence of electrolytes. Clint, Rubingh, Motomura’s and Rosen’s
3
approaches have been utilized to obtain various parameters related to mixed micelles.
4
2. Materials and Experimentals
ip t
1
The anionic surfactant, SDBS and amphiphilic drug, IBF were the products of
6
Sigma with purity >98%. Pyrene, used as micellar probe in the fluorescence
7
measurements, was a Sigma product with purity >98%. A stock solution of pyrene was
8
prepared in absolute methanol. All solutions were prepared in double-distilled water of
9
specific conductivity: (10 to 50) μS cm-1 and experiments were done under thermostatic
an
us
cr
5
conditions at 298.15 K with accuracy of ±0.1 K.
11
2.1 Surface tension measurements
d
M
10
The cmc was determined by the surface tension () measurement. Sigma 700
13
(Attention) performed the experiments using a platinum ring, the ring detachment method
14
in a calibrated tension at a constant temperature of 298.15 K. Detailed procedure has been
15
reported earlier [20]. Each experiment was repeated at least three times.
16
2.2 Electronic absorption measurements
Ac ce p
te
12
17
UV-visible spectroscopy investigations have been carried out to understand the
18
IBF-SDBS interactions. The absorbance spectra were recorded on an Evolution 300 UV-
19
vis spectrometer with a quartz cuvette.
20
5 Page 5 of 31
1
2.3 Fluorescence measurements The micellar aggregation number (Nagg) of single and mixed amphiphilic solutions
3
was determined by steady-state fluorescence quenching measurements. Pyrene was used
4
as a probe and cetylpyridinium chloride (CPC) as quencher throughout the study. The
5
steady-state fluorescence experiments were performed with a Hitachi F-7000
6
spectrofluorometer, connected to a PC. A 3 cm3 silica cell was used for the spectral
7
measurements at a constant temperature. By selecting 335 nm as the excitation
8
wavelength of the fluorescence probe (pyrene), the emission spectra of solution
9
components prepare in pyrene were recorded from 350 to 450 nm. The first and third
10
vibronic peaks of pyrene appear at 373 and 384 nm respectively (Fig. 1). At a constant
11
probe concentration of 1 × 10-6 M, the quencher concentration was varied from 0 to 1
12
×10-5 M to ensure a Poisson distribution for equilibration of solubilizates between
13
micelles.
15
cr
us
an
M
d
te
Ac ce p
14
ip t
2
3. Results and discussion
16
The aqueous solubility of IBF more than 1500 mM was checked and is found to be freely
17
soluble in water. Figure 2 shows plots of surface tension versus [total amphiphile] in the absence
18
and presence of 100 mM NaCl. The cmc value of the pure IBF was found to be 180 mM in water
19
at 298.15 K, which agrees well with the previously reported value in the literature (179 mM)
20
[21]. The cmc values of pure SDBS also agree well with the literature (Table 1) [22]. As the
21
hydrophobic group of the drug (IBF) molecule is rigid, it is difficult for the drug molecules to
22
adjust in the curved area of a micelle. Therefore, the drug forms micelles, but at high 6 Page 6 of 31
concentrations, as compared to the surfactant (SDBS). The drug molecules will not choose the
2
sites between the head groups due to electrostatic repulsion, but they can still choose the second
3
site around the exterior surface of anionic micelles, i.e., between the stern layer and shear
4
surface. The IBF ions residing outside the stern layer may now be considered to form ion-pairs
5
with the sodium counterions present in the stern layer. This is schematically; shown in Scheme 1
6
(b).This fashion of adsorption of drug molecules reduces magnitude of work for micellization
7
thus decreasing cmc. In the presence of NaCl (Fig. 2 (b)), the cmc of IBF was lowered, whereas
8
no significance change was observed for cmc of SDBS. The cmc of mixed systems of a particular
9
composition decreases further on adding inorganic salt (100 mM NaCl). The depression of cmc
10
in the presence of electrolytes is due to screening effect of the salt (the thickness of the electric
11
double layer surrounding the ionic head groups and consequent decrease electrical repulsion
12
between them in the micelle). The cmc values of the mixed systems usually fall in between the
13
values of pure components in the presence and absence of salt (100 mM NaCl). This means that
14
the mixed micelles are formed due to attractive interactions between the two components.
15
Results presented in Table 1, clearly indicate that the large decrease in cmc of drug + surfactant
16
is in the presence of NaCl.
cr
us
an
M
d
te
Ac ce p
17
ip t
1
For ideal mixtures, cmc of mixed systems can be predicted using Clint’s model [23,24]:
18
1 i cmcideal cmci
19
where αi and cmci are the stoichiometric mole fraction and cmc of ith component under the
20
similar experimental conditions. For the binary drug–surfactant systems, the equation becomes
21
1 1 2 cmcideal cmc1 cmc2
(1)
(2)
7 Page 7 of 31
cmc1 and cmc2 are the cmc of the pure surfactant (SDBS) and drug (IBF), respectively, and α1
2
and α2 are their mole fractions. The theory is over simplication and idealization, which considers
3
that the individual components are non-interacting, and their individual cmc values reflect their
4
relative tendency towards mixed micellization. Any deviation from cmcideal would, however,
5
account for interactions among amphiphiles. Divergence in positive and negative sides indicates
6
antagonism and synergism, respectively, in the system. In these systems, the cmc values come
7
out to be lower than cmcideal values– this indicates that the drug–surfactant mixed micelles are
8
formed by attractive interactions between the IBF and anionic SDBS, which is also an indication
9
of nonideal behavior of mixing. Therefore due to attractive interaction between the components
10
(IBF and SDBS) cmcid values comes out to be more than experimental cmc values. The cmc
11
values have been used to determine the composition of the mixed micelles and the micellar
12
molecular interaction parameter (β) among the components by applying the phenomenological
13
models given by Rubingh [25]. The fundamental equations of Rubingh’s model are:
14
[ln (cmcexp 1 / cmc1 X 1 )] /(1 X 1 ) 2
15
Where X1
cr
us
an
M
d
te
(3)
Ac ce p
16
ip t
1
(4)
17
X1 is micellar mole fraction of surfactant (component 1). The X1 values for mixed systems
18
increase with increase in surfactant concentration (Table 1). With the increase in concentration of
19
surfactant in the solution, contributions of surfactants in the mixed micelles also increase. In all
20
systems, X1 is always greater than α1. As the micelle mole fraction of surfactant in the solutions
21
is very small, the micelles in the ideal state should contain less surfactant. It seems that the added 8 Page 8 of 31
1
surfactant replaces some of the drug molecules from the mixed micelles resulting in some
2
reduction in steric hindrance in the micellar core. Hence, more surfactant is present in mixed
3
micelles as compared to the ideal state. All the results and discussion given above indicate synergistic interactions between the
5
two components of the mixed micelles. As such, the interaction parameter, β, comes out to be
6
negative at all mole fractions. The values are greater in the presence of NaCl, which are in line
7
with the X1 values. On adding the NaCl, the attractive interaction between two amphiphiles
8
increases. For the mixture of like charged ionic amphiphiles, the contributions to the interaction
9
between the amphiphiles are from Van der Waals interaction between the tails of the amphiphiles
10
and the repulsive interaction between the head groups. The interaction between the tails is
11
negative and that between the heads is positive. With the addition of NaCl, the repulsive
12
interaction between the like charged head groups decreases because of high ionic strength in the
13
solution, which in turn makes β becoming more negative. The β becoming more negative due to
14
addition of NaCl to the present mixed system is similar to the reported earlier [26,27].
16 17 18
cr
us
an
M
d
te
The values of β are used to calculate the activity coefficients of the components using the
Ac ce p
15
ip t
4
following equations:
(5) (6)
19
From Eqs. (5) and (6), the β and X1 values are used for evaluating f1 and f2. The values of activity
20
coefficients for systems are less than unity (Table 1) indicating non-ideal behavior for mixed
21
micelles.
9 Page 9 of 31
Motomura and Aratono [28] developed a model that is an attempt to overcome the
2
limitations of Rubingh’s regular solution theory and improved the predictions of phase
3
separation model. Basically, it is a thermodynamic method that considers mixed micelles as a
4
macroscopic bulk phase where the energetic parameters of such systems can be evaluated in
5
terms of excess thermodynamic quantities. In the present study, only the micellar mole fraction
6
of mixed systems in the ideal state (X1id) has been computed using Motomura’s approximation as
7
follows:
8
X1
9
It is evident from the Table 1 that X1 values are less than X1id for all the mole fractions, indicating
10
that the mixed micelles formed by these systems contain more contribution of IBF than in its
11
ideal mixing state.
12
3.1 Interfacial phenomenon
us
(7)
M
an
1cmc2 1cmc2 2 cmc1
te
d
id
cr
ip t
1
Amphiphiles orient at the air/water interface and decrease the surface tension. The
14
physical properties of the interface can be very important in all types of natural phenomena and
15
industrial processing operations. Many industrial processes involve colloidal dispersions, such as
16
foam, emulsions and suspensions, all of which contain large interfacial areas and hence the
17
properties of these interfaces may also play a large role in determining the properties of the
18
dispersions themselves. On the basis of adsorption isotherm, maximum surface excess
19
concentration at air/water interface, Γmax can be calculated by using the Gibbs adsorption
20
equation in the following form [27]:
Ac ce p
13
(8)
21
10 Page 10 of 31
Where (d/dlog S) is the maximum slope, is the surface tension of the solution. R and T are the
2
gas constant and absolute temperature, respectively. n is introduced to allow simultaneous
3
adsorption of cation and anion. The value of n is used as 2; but in the presence of NaCl an
4
excess amount of Na+ in 100 mM NaCl, n = 1[29]. The higher the Γmax, steeper is the approach to
5
cmc and higher the surface activity. Γmax increases with the addition of NaCl (Table 2) which is a
6
general trend observed in single amphiphile solutions and such a variation in Γmax is attributed to
7
the salting-out effect of the added electrolyte. Moreover, counterion binds to the adsorption layer
8
and reduces the repulsive interaction between the head groups of the adsorbed ionic amphiphiles
9
causing enhancement of adsorption or increase of Γmax. The Γmax values were further used to
10
evaluate the minimum area per surfactant molecule, Amin at the air/water interface using the
11
following equation
M
an
us
cr
ip t
1
(9)
te
d
12
NA in this equation is the Avogadro number. These values suggest whether the amphiphile is
14
closely packed of loosely packed at air/water interface. The Amin values are lower in mixed
15
amphiphile system than the pure components. The low Amin values suggest that the amphiphiles
16
are closely packed so their orientation is almost perpendicular to the interface. In the presence of
17
NaCl, the Amin values for mixed system are higher than the SDBS but lower than IBF.
18
Ac ce p
13
The interfacial composition ( X1 ) and interaction parameter (βσ) can be evaluated using
19
Rosen’s model [30], analogous to Rubingh’s model for mixed micelles, as:
20
[ln (Cmix 1 / C1 X 1 )] /(1 X 1 ) 2
(10)
(11)
21 11
Page 11 of 31
is the monolayer mole fraction of SDBS in the mixture, C1 , C 2 and Cmix are the
1
Where
2
molar concentrations in the solution phases of mixture, component 1 and component 2,
3
respectively, at a particular mole fraction of component 1 required to produce a given value.
4
Values of
5
surfactant than the mixed micelles. Due to the rigid ring system of the drug molecules prefer the
6
monolayer and, therefore, less surfactant is present in the monolayer. In the absence of
7
electrolyte, the average βσ values are greater than β.
8
3.2 Thermodynamic parameters
ip t
cr
us
an
10
The standard free energy of micellization (
) is calculated in accordance with the
pseudophase model using the following equation [31]
M
9
are lower than X1 values indicating that the mixed monolayer contains less
d
11
(12)
Where Xcmc, is the cmc of the mixture in mole fraction unit. The
13
all the binary systems have considerable spontaneity of micellization. The standard Gibbs energy
14
of adsorption,
Ac ce p
15
values (Table 2) reveal that
te
12
, is related to Gibbs energy of micellization through relation[32,33]: (13)
16
where Π cmc is the surface pressure at the cmc and is equal to (0 − cmc) where 0 is the surface
17
tension of pure solvent and cmc is that of the solution at the cmc. The values of
18
are all negative and greater than
19
adsorb at the interface and then form mixed micelles. The values of pure components are less
20
negative than those of the mixtures, indicating that the mixed systems are more active than those
21
of the pure components.
(Table 2)
(in magnitude). This shows that amphiphiles first try to
12 Page 12 of 31
The molar Gibbs energy at the maximum adsorption attained at cmc, Gmin, is given by
1 2
[34]: (14)
ip t
3
It is the minimum Gibbs energy of the given surface with fully adsorbed amphiphile molecules.
5
The lower the value of the Gibbs energy the more thermodynamically stable is the surface
6
formed.
us
cr
4
The excess free energy of micellization, ∆Gex, can be calculated by the equation
an
7 8
(15)
The negative values suggest that the mixed micelles are more stable than the micelles of
10
pure amphiphiles. Mixed micelles have fairly different physicochemical properties from those of
11
pure micelles of individual components. From the application point of view, mixed micelles are
12
of great importance in biological, technological, pharmaceutical and medicinal formulation,
13
enhanced oil recovery process for the purpose of solubilization, suspension, dispersion, etc. It
14
was found that the cmc of mixed amphiphiles was lower than either of the individual
15
amphiphiles which is greatly valuable because it decreases the total amount of amphiphile used
16
in meticulous purpose leading in lessening of cost and environmental affect. Therefore micelle
17
formed by mixing of two components is more stable in contrast to micelle form by single
18
component. Micelles formed in the electrolyte solution are more stable shown by results (Table
19
2).
Ac ce p
te
d
M
9
20 21
13 Page 13 of 31
1
3.3 Micro-environment and aggregation number Fluorescence spectroscopy has been successfully used for the study of central issues of
3
solutions of amphiphiles. Different techniques and methods are uniquely adapted to investigate
4
problems in this field. The extrinsic and intrinsic probes can be used, to provide information on
5
molecular association, microstructure and molecular dynamics. This constitutes an important
6
contribution to the understanding and control of microscopic properties, as well as to their
7
biological functions and technical applications. One of the most popular fluorescent probes is
8
pyrene. Its emission spectrum depends strongly on the solvent in such a way that the relative
9
intensity of I and III bands has been empirically related to environment polarity, and, therefore,
10
gives specific information on the absence or presence of micelles or other hydrophobic domains.
an
us
cr
ip t
2
The quenching of fluorescence probe will depend on its confinement in a micro domain,
12
such as a micelle or a micro emulsion droplet. From the fluorescence decay parameters the
13
concentration of micro domains can be obtained and from this the aggregation numbers can be
14
determined. In the general case of a micellar solution containing low concentrations of a
15
luminescence probe and of a quencher, there are empty micelles with either luminescent probe or
16
quencher, and micelles with both probe and quencher. The luminescence intensity can, under
17
certain conditions, be assumed proportional to the concentration of probe molecules in micelles,
18
which contain no quencher. For the simplest case, where the micelles are small and mono
19
disperses, the determination of aggregation numbers is straightforward. The probe and quencher
20
distribution are assumed stationary, following a poisson distribution.
Ac ce p
te
d
M
11
21
If a micellar solution contains an unknown micelle concentration [M] and a quencher of
22
concentration [Q], adding a luminescent probe, pyrene, to the micellar system will enable it to
23
partition both among micelles with quencher and with empty micelles. If probe molecule is
14 Page 14 of 31
1
luminescent only when it occupies an empty micelle, then the measured ratio of intensities in
2
presence (I) and absence (Io) of quencher is related as [35,36]
3
I ln Io
4
[M] can be written as
5
[M]
6
where [S]T is the total concentration of surfactant mixture, Nagg is the micellar aggregation
7
number.
8
Combining Eqs. (16) and (17) leads to
9
N agg [Q] I ln o I [S]T cmc
[Q ] [M ]
cr
ip t
(16)
(17)
(18)
d
M
an
us
[S]T cmc N agg
Eq. (18) predicts a linear plot between ln(Io/I) and [Q] with a slope equal to Nagg/([S]T)-cmc),
11
which gives the values of Nagg (Fig. 3). Aggregation number of ionic amphiphiles is reported to
12
increases in the presence of NaCl (Table 3). The added electrolyte tend to decrease the area per
13
amphiphile molecule by better screening of electrostatic repulsion between the ionic heads as a
14
result of increase in the number of counter ions in the Stern diffuse layers.
Ac ce p
te
10
15
The above results can further be explained on the basis of quenching. The strength of
16
hydrophobic environment can be evaluated by determining the first order quenching rate
17
constant, the so called Stern-Volmer binding constant (Ksv) [37], using the relation:
18
Io 1 K sv [Q] I
(19)
15 Page 15 of 31
Ksv gives an idea about bimolecular quenching and unimolecular decay as it being the product of
2
rate constant of the quenching process and lifetime of the probe in the absence of bimolecular
3
quenching [38]. Greater the solubility of the probe and quencher, higher would be the Ksv value.
4
High Ksv values (presented in Table 3) suggest an increase in quenching due to presence of both
5
pyrene and quencher in strong hydrophobic environment.
ip t
1
The results are further explained on the basis of micropolarity of the microenvironment
7
of mixed micelles over the whole mixing range. The I1/I3 ratio is directly related to the
8
environment in which pyrene is solubilized and senses the degree of hydrophobicity of that
9
environment. The ratio of intensity of the first and third vibronic peaks, i.e., I1/I3, of the pyrene
10
fluorescence emission spectrum in the presence of surfactant is considered the index of
11
micropolarity of the system. A value less than 1 generally indicates that pyrene is in the non-
12
polar environment while values greater than 1 mean pyrene having a polar surrounding [38].
13
Characteristic values of I1/I3 of pyrene in some solvents are 0.6 in cyclohexane; 1.04 in toluene;
14
1.23 in ethanol; 1.33 in methanol and 1.84 in water [38]. The average values of I1/I3 ratio at
15
different quencher concentrations are also given in Table 3. These values are close to the I1/I3
16
ratio for methanol and ethanol.
us
an
M
d
te
Ac ce p
17
cr
6
The apparent dielectric constant (D) of the medium can be estimated by the relation [37]:
18
I1 1.00461 0.01253D I3
19
The values given in Table 3 show that there is no definite trend in D values. These values are
20
close to the D values for methanol and ethanol [39], again confirming that the solubilized pyrene
21
is in a short alcohol-like environment. The ideal dielectric constant inside the mixed micelle can
22
be computed from the following relation:
(20)
16 Page 16 of 31
(21)
1
It is clear from Table 3 that the experimental values are somewhat different from the calculated
3
values. This is because IBF has some attractive interactions inside the micelle.
4
3.4 Effects of IBF concentration on the UV-vis absorption spectra of SDBS
ip t
2
The absorption spectra of SDBS+IBF in the presence and absence of NaCl are presented
6
in Fig 4. The pure SDBS exhibits two absorbtion band at 260 and 230 with or without
7
electrolyte. On the addition of IBF, the absorption of monomer band increases. The increase in
8
absorption with increase IBF concentration is due to the interaction of SDBS with IBF.
us
cr
5
10
an
9
4. Conclusion
The interfacial and micellar behavior in the mixture of SDBS and IBF amphiphile
12
systems in the absence and presence of electrolyte (100 mM NaCl) were studied. We observed
13
that, in the absence of electrolyte the attractive interaction in the mixed micelle is lower than that
14
in mixed monolayer at the air/water interface. However, the β, βσ values are negative, which
15
indicates that there is synergistic interaction in both micellar and monolayer states and in the
16
absence and presence of an electrolyte. This study has confirmed that the synergism in mixed
17
micelle formation can be enhanced by adding salt. The negative values of
18
mixed micelles are more stable than the micelles of pure amphiphiles. Micelles formed in the
19
electrolyte solution are more stable. The Nagg values of mixed surfactant system are lower than
20
SDBS. The degree of negative deviation in I1/I3 values increases with NaCl in comparison to
21
their absence. The value of Ksv of mixture increases with NaCl. The experimentally determine
22
and calculated apparent dielectric constants for our systems are lower than that of ideal one
23
because of attractive interaction inside the micelle.
Ac ce p
te
d
M
11
suggest that the
17 Page 17 of 31
1
3 4
Acknowledgments Chemistry Department and Centre of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah are highly acknowledged.
ip t
2
cr
5
us
6
an
7 8
M
9
13 14 15
te
12
Ac ce p
11
d
10
16 17 18
18 Page 18 of 31
1
3
References [1]
C. Tanford, The Hydrophobic Effect: Formation of Micelles &Biological
ip t
2
Membranes; Wiley Publishing, New York, 1980.
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M.S. Alam, D. Samanta, A. B. Mandal, Colloids Surf. B: Biointerfaces 92 (2012) 203– 208.
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R.G. Alargova, I.I. Kochijashky, M.L. Sierra, K. Kwetkat, R. Zana, J. Colloid Interface Sci. 235 (2001) 119-129.
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ip t
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R. M. Hill, in: K. Ogino, M. Abe (Eds.), Mixed Surfactant Systems, Surfactant Science Series, vol. 46, Dekker, New York, 1993.
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K. Motomura, M. Aratono, Mixed Surfactant Systems, Dekker, New York, 1998.
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M.J. Rosen, Surfactants and Interfacial Phenomena, John Wiley & Sons, New York,
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ip t
1
[33]
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us
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N.J. Turro, A. Yekta, J. Am. Chem. Soc., 100 (1978) 5951-5952.
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an
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1992.
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K. Kalyanasundram, J.K. Thomas, J. Am. Chem. Soc. 99 (1977) 2039-2044.
14
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16 17 18 19
te
Ac ce p
15
d
13
20 21 22 23
21 Page 21 of 31
1 2
Caption
4
Table 1. Various physicochemical properties of SDBS+IBF mixed amphiphilic systems.
5
Table 2. Various interfacial properties and energetic parameters of SDBS and IBF mixed
6
amphiphilic system.
7
Table 3. Aggregation number (Nagg), Stern-Volmer binding constant (Ksv), micropolarity (I1/I3),
8
and apparent dielectric constant (D) for SDBS and IBF mixed amphiphilic systems.
9
Scheme 1. Schematic diagram showing (a) chemical structure of Ibuprofen (IBF), (b) ion pair
an
us
cr
ip t
3
interaction between SDBS micelle and IBF.
11
Fig. 1. Representative fluorescence (emission) spectra of 10−6 M pyrene in 100 mM NaCl
12
solution of SDBS + IBF (4:6) at different quencher concentrations (maximum intensity indicates
13
no quencher and minimum intensity indicates maximum amount of quencher).
14
Fig. 2. Plots showing variation of surface tension () with log [S] at 298 K (a) in absence of salt
15
(b) in presence of 100 mM NaCl (c) pure IBF.
16
Fig. 3. Plots for determination of aggregation number (Nagg) of SDBD + IBF mixed systems in
17
100 mM NaCl solution.
18
Fig. 4. Absorption spectra of SDBS in presence of different concentration of IBF (A) with NaCl
19
(B) without NaCl.
Ac ce p
te
d
M
10
20 21 22 23 22 Page 22 of 31
1 2
Table 1. αSDBS
cmcid (mM)
cmcexp (mM)
β
X1
Xideal
f1
-3.28
0.825
0.975
-2.79
0.913
-2.97
0.947
-3.71
0.976
0.6 0.8 1.0
5.61
4.29
2.85
2.57
1.91
1.80
1.44
1.40 1.15 [1.59]
b
1.15
0.6 0.8
1.0
5 6 7 8
0.257 0.204 0.195
1.13
2.84 1.91 1.43
0.990
0.979
0.097
0.995
0.991
0.069
0.998
0.997
0.029
-13.26
0.616
0.971
0.141
0.006
-14.71
0.635
0.989
0.140
0.002
-15.26
0.655
0.995
0.162
0.001
-15.63
0.679
0.998
0.199
0.001
1.13
The uncertainty limits of cmc is ±2%. a
Ac ce p
4
0.501
159 5.59
d
0.4
159
te
0.0 0.2
0.107
M
SDBS + IBF + 100 mM NaCl
0.904
us
0.4
180
180 [179]a
an
0.2
cr
SDBS + IBF 0.0
f2
ip t
3
Literature value [21]
b
Literature value [22]
9 10 11
23 Page 23 of 31
1 2
Table 2. Cσideal (mM)
Xσ
βσ
107 Γmax (mol m–1)
Amin (nm2 molecule–1)
П
Gm (kJ mol-1)
SDBS + IBF 0
2.61
2.61
Gad (kJ mol-1)
Gmin (kJ mol-1)
ip t
Cσmix (mM)
αSDBS
cr
3
Gex (kJ mol-1)
11.19
1.48
38.26
-41.80
-45.22
0.283
–
22.87
0.72
39.26
-45.92
-47.63
0.134
-1.174
0.496
0.589
0.4
0.408
0.332
0.006
-8.76
26.10
0.63
37.91
-46.40
-47.85
0.123
-0.549
0.6
0.267
0.231
0.162
-4.29
22.59
0.73
37.42
-47.45
-49.10
0.144
-0.369
0.8
0.199
0.177
0.515
-2.84
26.72
0.62
37.42
-48.18
-49.58
0.122
-0.215
1
0.14
0.144
13.12
1.26
37
-48.99
-51.81
0.251
0
17.00
17
40.29
-37.16
-39.83
0.197
42.34
-49.23
-50.56
0.086
-7.773
0.43
42.59
-44.80
-45.91
0.072
-8.450
0.45
0.130
0.4
0.78
0.780
0.001
0.6
0.56
0.56
0.8
0.44
0.44
1
0.41
0.41
6
0.135
-.37
36.44
0.617
-4.72
28.20 44.34
te
5
38.10
an
-45.61
-46.78
0.075
-8.547
42.39
-46.21
-47.72
0.097
-8.440
0.37
42.14
-46.39
-47.34
0.062
Table 3.
105Ksv
I1/I3
Dexp
Dideal
0.03 1.59 0.84 0.81 1.07 1.63
1.26 1.62 1.33 1.28 1.13 1.27
21 49 26 22 10 19
21 19 19 19 19 19
SDBS + IBF + 100 mM NaCl 0.0 88 1.38 1.23 0.2 115 1.64 1.12 0.4 117 0.67 1.11 0.6 139 0.99 1.09 0.8 175 1.74 1.24 1.0 205 0.76 1.09
19 09 08 07 18 07
19 12 11 11 11 07
α1 Nagg SDBS + IBF 0.0 57 0.2 31 0.4 76 0.6 86 0.8 120 1.0 140
7
42.39
0.58
The uncertainty limits of ∆Gm, ΔGad, Gmin, and Gex ±3%, ±4%, ±4% and ±4%, respectively.
Ac ce p
4
-4.85
M
0.13
d
0.2
–
SDBS + IBF + 100 mM NaCl 15.11 1.09 – 31.95 0.51
us
0.2
–
The uncertainty limits of Nagg is ±3%. 24 Page 24 of 31
1
M
an
us
cr
ip t
2
– + – +
–
+
Ac ce p
+
te
d
(a)
–
–
O
O
+ –
–
–
+
–
+
+
SDBS micelle
Ibuprofen
(b) 3
25 Page 25 of 31
1
Scheme 1.
2
ip t
3
us
cr
4
2500
an
Intensity
2000
1500
500
0 360
380
M
1000
400
420
440
5 6 7
Fig. 1.
Ac ce p
te
d
wavelength (nm)
26 Page 26 of 31
70
SDBS= 0.2 SDBS= 0.4
65
SDBS= 0.6
60
SDBS= 0.8
50 45
cr
/ mNm
-1
ip t
55
40
30 -4.0
-3.6
-3.2
-2.8
-2.4
-2.0
an
log [S] (M)
us
35
M
(A)
SDBS= 0.4 SDBS= 0.6 SDBS= 0.8
te
35
Ac ce p
/ mNm
-1
45
40
SDBS= 0.2
d
50
30
25
-4.8
-4.4
-4.0
-3.6
-3.2
log [S] (M)
(B)
27 Page 27 of 31
60
without NaCl with NaCl
55
ip t
45
40
cr
/ mNm
-1
50
30 -1.8
-1.6
-1.4
-1.2
-1.0
(C)
Fig. 2.
-0.6
-0.4
M
1
-0.8
an
log [IBF] (M)
us
35
12
te
d
2
SDBS= 0.2
Ac ce p
SDBS= 0.4
10
SDBS= 0.6 SDBS= 0.8
ln I0 / I1
8
6
4
2
0 0.00000
0.00002
0.00004
0.00006
0.00008
[CPC] (M)
3 4
Fig. 3.
28 Page 28 of 31
5
ip t
3
1
0
200
cr
2
[IBF](mM) 0 20 40 80 120 160 180 200 220
240
260
280
(A)
M
2
7
d
6
te
4 3
Ac ce p
Absorbance
5
300
an
Wavelength(nm)
1
us
Absorbance
4
[IBF](mM) 0 20 40 80 120 160 180 200
2 1 0
200
3 4 5
220
240
260
280
300
Wavelength(nm)
(B)
Fig. 4.
6
29 Page 29 of 31
Research Highlights
2 3
1. Mixed micelles formed in the presence of electrolyte are more stable in comparison to its absence.
4
2. The synergism in mixed micelle formation can be enhanced by adding salt.
5
3. Ibuprofen form ion-pairs with the sodium counterions of the surfactant.
ip t
1
Ac ce p
te
d
M
an
us
cr
6
30 Page 30 of 31
1 2
Graphical Abstract
3
–
+
–
–
– +
–
–
+ +
+
–
+
M
–
–
an
+
SDBS micelle
8 9 10
te
7
Schematic diagram showing ion pair interaction between SDBS micelle and IBF.
Ac ce p
6
Ibuprofen
d
5
O
us
+
cr
O
ip t
4
31 Page 31 of 31