Chapter-I

General Introduction

Amphiphile is a term describing a chemical compound possessing both

hydrophilic (water-loving) and lipophilic (fat-loving) properties. Such a compound

is called amphiphilic or amphipathic. It is derived from Greek word amphi,

meaning both, and terms relates to the facts that all surfactant molecules consist of

at least two parts, one which is soluble in specific fluid (the lyophilic part) and one

which is insoluble (the lyophobic part). When the fluid is water, one usually talks

about the hydrophobic and hydrophilic parts, respectively. A hydrophilic molecule

or portion of a molecule is one that is typically charge-polarized and capable of

hydrogen bonding, enabling it to dissolve more readily in water than in oil or other

hydrophobic solvents. Hydrophilic and hydrophobic parts of molecules are also

known as polar and non-polar, respectively. Hydrophobic portion of molecules in

water often cluster together forming micelles. Water on hydrophobic surfaces will

exhibit a high contact angle.

Amphiphilic compounds bear an ionic (cationic, anionic, or zwitterionic) or

non-ionic polar head group and a hydrophobic portion. In aqueous medium, they

are able to organize themselves as micelles, bilayers, monolayers, hexagonal or

cubic phases. Aggregation is not, however, just limited to aqueous solution; it is

sometimes observed in non-aqueous polar solvents such as ethylene glycol and

non-polar solvents such as hexane (in the latter case giving rise to inverse

structures) [1]. The extent of the hydrophobic and hydrophilic portions determines

the extent of partitioning. The spatial separation between the polar and non-polar

moieties, as well as molecular shape [2] and hydrophilic and hydrophobic balance

[3], determines their tendency to form the different structures, which eventually

can be interconverted as a function of pH, temperature, ionic strength, and

concentration. Alkyl chain-containing surfactants seem to associate according to

phase separation model. Normally, these micelles exhibit aggregation numbers

between 50 and 200 [4]. The amphiphile with more or less equilibrated

hydrophilic and lipophilic tendencies are likely to migrate to surface or interface.

It doesn‟t happen if the amphiphilic molecule is too hydrophilic or too

hydrophobic, in which case it stays in one of the phases. Because of its dual

affinity, an amphiphilic molecule doesn‟t feel „at ease‟ in any solvent. This is why

amphiphilic molecules exhibit a very strong tendency to migrate to interface or

surfaces and to orientate so that the polar group lies in water and the non-polar or

apolar is placed out of it. Amphiphiles often exhibit other properties besides

lowering of surface tension.

Amphiphiles play a key role in the existence of the life and widely used in

the industry, medicine, pharmacology, etc. [5, 6]. The single features of

amphiphiles that give rise to broad utility is their ability to coexist with and

function as an interface between polar and non-polar phases. This ability is

determined by a balance between ionic and dipolar interactions with polar media

and dispersion interactions with non-polar media.

Solutes showing hydrophobic self-association may be classified into four

categories on the basis of chemical structure: (1) flexible chain compounds

(surfactants, etc.), (2) aromatic or heterocyclic ring or fused ring structures (drugs,

dyes, etc.), (3) alicyclic fused ring compounds (bile salts, etc.), and (4)

macromolecular solutes (proteins, etc.) [7]. The self-association behavior must

relate to the chemical structure of solutes. The simplest type of association, viz.,

dimerization, may take place in all the self-associating systems being considered.

The formation of higher multimers may overshadow it, however, more or less

completely [7].

Surfactants and Their Classification

The term surfactant is a blend of surface active agent [8]. Surfactants are

usually organic compounds that are amphiphilic, meaning they contain both

hydrophobic groups (their tails) and hydrophilic groups (their heads). Therefore,

they are soluble in both organic solvents and water. The term surfactant was

coined by Antara products in 1950. In Index Medicus and the United States

National Library of Medicine, surfactant is reserved for the meaning pulmonary

surfactant. The tail part may consist of one or more hydrocarbon chains, usually

with 6-22 carbon atoms. The chains may be linear or branched, may contain

unsaturated portions or aromatic moieties, and may be partly or completely

halogenated (as in fluorocarbon surfactants) while a charged or uncharged

hydrophilic species (group) acts as the head part of the molecule. The hydrocarbon

chain interacts weakly with the water molecules in an aqueous environment,

whereas the polar or ionic head group interacts strongly with water molecules via

dipole or ion–dipole interactions. It is this strong interaction with the water

molecules that renders the surfactant soluble in water.

Surfactants reduce the surface tension of water by adsorbing at the liquid-

gas interface. They also reduce the interfacial tension between oil and water by

adsorbing at the liquid-liquid interface. Many surfactants can also assemble in the

bulk solution into aggregates. Examples of such aggregates are vesicles and

micelles. Thermodynamics of the surfactant systems are of great importance,

theoretically and practically [9]. This is because surfactant systems represent

systems between ordered and disordered states of matter. Surfactant solutions may

contain an ordered phase (micelles) and a disordered phase (free surfactant

molecules and/or ions in the solution).

Surfactants have been widely used in both industrial and domestic fields

since the first surface-active product was prepared commercially by C. Schollar in

Germany in 1930 [10]. Surfactants have impact on almost all aspects of our daily

life, either directly in household detergents and personal care products or

indirectly in the production and processing of materials which surround us [10-

14]. Surfactants have even been the subject of investigation into the origin of life,

meteorites containing lipid- like compounds and may be an interstellar prebiotic

earth source of cell membrane materials [15]. Moreover, surfactants play a major

role in the oil industry, for example in enhanced and tertiary oil recovery. They are

also occasionally used for environmental protection, e.g., in oil slick dispersants.

Some surfactants are known to be toxic to animals, ecosystems and humans, and

can increase the diffusion of other environmental contaminants [16-18]. Despite

this, they are routinely deposited in numerous ways on land and into water

systems, whether as part of an intended process or as industrial and household

waste. Some surfactants have proposed or voluntary restrictions on their use.

A surfactant can be classified by the presence of formally charged groups in

its head. A non-ionic surfactant has no charge groups in its head. The head of an

ionic surfactant carries a net charge. If the charge is negative, the surfactant is

more specifically called anionic; if the charge is positive, it is called cationic. If a

surfactant contains a head with two oppositely charged groups, it is termed

zwitterionic.

(i) Cationic surfactants

The vast majority of cationic surfactants are based on the nitrogen atom

carrying positive charge. Both amine and quaternary ammonium-based products

are common [19, 20]. A common class of cationics is the alkyl trimethyl

ammonium chloride, where R contains 8–18 C atoms. Primary, secondary or

tertiary amines of cationic surfactants are pH dependent. Primary amines become

positively charged at pH < 10, secondary amines become charged at pH < 4. The

prime use of cationic surfactants is their tendency to adsorb at negatively charged

surfaces, e.g., anticorrosive agents for steel, flotation collectors for mineral ores,

dispersants for inorganic pigments, antistatic agents for plastics, other antistatic

agents and fabric softeners, hair conditioners, anticaking agent for fertilizers and

as bactericides.

Examples: Dodecyltrimethylammonium bromide CH3 (CH2)11N+

(CH3) Br–

Dodecylamine hydrochloride CH3 (CH2)11N+H3 Cl

–

(ii) Anionic Surfactants

The surface-active portion of the molecules bears a negative charge.

Carboxylate (CnH2n+1COO–X

+), sulfate (CnH2n+1OSO3

–X

+), and sulfonate

(CnH2n+1SO3–X

+), are the polar groups found in anionic surfactants. These are the

most widely used class of surfactants in industrial applications [21, 22] due to their

relatively low cost of manufacture. Anionics are used in most detergent

formulations and the best detergency is obtained by alkyl and alkylarye chains in

the C12–C18 range. The counterions most commonly used are sodium, potassium,

ammonium, calcium and various protonated alkyl amines.

Examples: Sodium laurate NaCOO)(CHCH 1023

Sodium dodecylbenzene sulfonate NaSOHC)(CHCH 3461123

(iii) Non-ionic surfactants

The surface-active portion of the molecules bears no apparent ionic charge.

Non-ionic surfactants have either a polyether or a polyhydroxy unit as the polar

group. In the vast majority of non-ionics, the polar group is a polyether consisting

of oxyethylene units, made by polymerization of ethylene oxide. Several classes

can be distinguished: alcohol ethoxylates, alkyl phenol ethoxylates, fatty acid

ethoxylates, monoalkanolamide ethoxylates, sorbitan ester ethoxylates, fatty amine

ethoxylates and ethylene oxide–propylene oxide copolymers (sometimes referred

to as polymeric surfactants).

Examples: Polyoxyethylene monohexadecyl ether OH)CH(OCH)(CHCH21221523

Polyoxyethylene octylphenylether 9.5422214

O)HO(CHC

(iv) Zwitterionic surfactants

Zwitterionic surfactants contain two charged groups of different sign.

Whereas the positive charge is almost invariably ammonium, the source of

negative charge may vary, although corboxylate is by far the most common.

Zwitterionics are often referred to as amphoterics. An amphoteric surfactant is one

that changes from net cationic via zwitterionics to net anionic on going from low

to high pH. Neither the acid nor the basic site is permanently charged, i.e.,

compound is only zwitterionic over a certain pH range.

The change in charge with pH of the truly amphoteric surfactants naturally

affects properties such as foaming, wetting, detergency, etc. These will all depend

strongly on solution pH. At the isoelectric point the physico-chemical behavior

often resembles that of non-ionic surfactants. Zwitterionic as a group are

characterized by having excellent dermatological properties. They also exhibit low

eye irritation and are frequently used in shampoo and other cosmetic products.

Common types of zwitterionic surfactants are N-alkyl derivatives of simple amino

acid, such as glycine (NH2CH2COOH), betaine (CH2)2NCH2COOH) and amino

propionoic acid (NH2CH2CH2COOH).

Examples: 3-(Dimethyldodecylammonio)-propane-1-sulfonate

332231123 SO)(CH)(CHN)(CHCH

N-Dodecyl-N,N-dimethyl betaine COOCH)(CHN)(CHCH 2231123

(iv) Polymeric surfactants

There has been considerable recent interest in polymeric surfactants due to

their wide application as stabilizers for suspensions and emulsions. These are

formed by association of one or several macromolecular structures exhibiting

hydrophilic and lipophilic characters.

Example: Polystyrene-block-poly(vinyl acetate)

–CHm

CH2

–

Br

Br

CC

O

)n

(CH2CH2OCH3

(v) Gemini surfactants

A surfactant usually contains only one polar group. Recently, there has

been considerable research intrest in a new class of surfactants, the gemini

surfactants [23-25] have generated interest in colloid chemistry due to their

superior performance over conventional surfactants in various industrial

applications. Gemini surfactants are also referred to as twin surfactants, dimeric

surfactants [8, 26], or bis surfactants. The term „Gemini surfactant‟, coined by

Menger, has become accepted in the surfactant literature for describing dimeric

surfactants, that is, surfactant molecules containing two hydrophobic groups and

two hydrophilic groups, connected by a linkage (spacer) close to hydrophilic

groups. A schematic representation of a gemini surfactant is shown in Fig.1.1.

Most geminis are composed of two identical halves, but unsymmetrical gemini

surfactants have also been synthesized, either having different hydrophobic tail

lengths, or different types of polar groups (heterogemini surfactants), or both. The

first reports on dimeric surfactants concerned bisquaternary ammonium halide

surfactants which were used to catalyze chemical reactions [27].

Tail Spacer TailHead Head

Fig.1.1: Schematic representation of a gemini surfactant.

Gemini surfactants are subject to much evaluation work at the present time

and one may foresee that the attractive features of these surfactants, such as high

efficiency, low cmc (at least one order of magnitude lower than for the

corresponding conventional (monomeric) surfactants, on a weight percent basis)

and surface tension values (10–100 times more efficient at reducing the surface

tension of water and the interfacial tension at an oil/water interface than

conventional surfactants), and a very steep rise in viscosity with concentration,

will find practical use. The high surfactant efficiency and the low cmc values have

triggered much effort into the potential use of gemini surfactants as solubilizers of

various kinds. In model experiments, using hydrocarbons as the compound to be

solubilized, geminis have been found to be better than conventional surfactants,

both on a molar and weight basis. Gemini is also of interest as lubricating agents

as a result of their tight packing at the surfaces. Some anionic gemini surfactants

have low Krafft temperatures, which make them applicable in cold water. Also,

cationic gemini surfactants possess interesting biological properties.

Much effort is also being devoted to exploit the specific geometry of

gemini surfactants to create structures of well-defined geometry. Gemini

surfactants form vesicles and liquid crystalline phase over broad concentration

ranges, a property that can be taken advantage of for a variety of applications. One

example of such work is the preparation of mesoporous molecular sieves. A

number of patents and papers have appeared in scientific literature [24, 25, 28,

29]. All charge types of gemini surfactants cationic [30, 31], anionic [32], non-

ionic [33] and zwitterionic [34] and a variety of structural types; alkylglucoside

based [35], sugar based [36], with unsaturated linkages [37] and almost all types

with flexible, rigid, and heterotype spacers have been synthesized. The search for

the synthesis of new novel types of gemini surfactants is increasing from their

application point of view [38, 39].

(vi) Bolaform Surfactants

Connecting two surfactant moieties towards the end of their hydrophobic

tail results in a so-called „bolaform surfactant‟ (Fig.1.2) and the physico-chemical

properties of such species are very different from those of conventional and

gemini surfactants. Their self-association ability is less, compared to conventional

ionic surfactants. However, they show biological activity [40, 41] and some

special bolaforms are capable giving rise to organized assemblies of peculiar

structure [42].

Fig.1.2: Schematic representation of a bolaform surfactant.

Micelle formation and critical micelle concentration

Micelle formation, or micellization, is an important phenomenon not only

because a number of important interfacial phenomena, such as detergency and

solubilization, depend on the existence of micelles in solutions, but also because it

affects other interfacial phenomena, such as surface or interfacial tension

reduction, that do not directly involve micelles.

The characteristic property of amphiphilic molecules is their capacity to

aggregate in solutions. The aggregation process depends on the amphiphilic

species and the conditions of the system at which they are dissolved. The

concentration at which this phenomenon occurs is called the critical micelle

concentration (cmc) [43, 44]. Micelle formation is primarily controlled by three

forces: the hydrophobic repulsion between the hydrocarbon chains and aqueous

solution, the charge repulsion of ionic head groups, and the van der Waals

attraction between the hydrocarbon tails [45, 46]. The length of the hydrocarbon

tail, size of the head group, and interaction of the hydrocarbon tails, with one

another and with the aqueous solution determines the size and shape of the

micelle, the cmc, and the aggregation number. Shapes of micelles can vary from

rough spheres to prolate ellipsoids, and the diameter of micelles generally ranges

from 3 to 6 nm [46]. This small diameter prevents micelles from being filtered

from solution and form appreciably scattering light. The term cmc was established

by Davis and Bury [47] defining it as a concentration range below which the

surfactant molecules in the solution remain as monomers and above which

practically all additional surfactants added to the solution form micelles. cmc is an

important property of the surfactants which reflects its micellization ability. Below

the cmc value, the physico-chemical properties of ionic surfactants resemble those

of strong electrolytes and, above the cmc, these properties change dramatically,

indicating a highly cooperative association is taking place. This is illustrated by

Preston‟s classic graph [43] in Fig.1.3. Just above the cmc, micellar structure is

considered to be roughly globular or spherical [4, 48].

Fig.1.3: Preston‟s classic graph showing variation in physical properties of

surfactant solutions below and above the cmc value of sodium dodecyl sulphate.

The determination of the value of cmc can be made by use of many

physical properties, but most commonly the breaks in electrical conductivity,

surface tension, light scattering, or fluorescence spectroscopy–concentration

curves have been used for this purpose. The cmcs also have very frequently been

determined from change in spectral characteristics of some dyestuff added to

surfactant solution when the cmc of the latter is reached. However, this method is

open to the serious objection that the presence of dyestuff may affect the value of

cmc. An excellent critical evaluation of the methods determining cmc is included

in a comprehensive compilation by Mukerjee and Mysels [44].

In a micellar solution, there is always a dynamic equilibrium between

surfactants monomers, monolayers and micelles (Fig.1.4).

Fig.1.4: Surfactant existence in different phases, dependent on surfactant

concentration.

Types of micelles

Normal micelle

Normal micelle structure just above the cmc can be considered as roughly

spherical [49-51]. In aqueous solution the hydrocarbon tails are oriented inward

and head groups are positioned into the bulk solvent [52]. The micelles are always

in dynamic equilibrium. The interior of a micelle is viewed as being much like a

liquid hydrocarbon droplet.

The micellar surface appears to be an amphipathic structure which is

supported by the binding of both hydrophobic organic molecules and hydrophilic

ions with micelles. The amphipathicity is a property shared with the surfaces of

proteins and membranes [53, 54]. Menger has proposed that water can penetrate

inside the micelle upto a certain level [55, 56], the idea get support from

fluorescence and 1H–NMR measurements. Partial molar volume determinations

indicate that the alkyl chains in the core are more expanded than those in the

normal liquid state [57].

An ionic micelle formed in polar solvents such as water generally consists

of three regions (Fig.1.5): (i) The interior or core of the micelle which is

hydrocarbon like as it consists of hydrocarbon chains of the ionic surfactant

molecules. (ii) Surrounding the core is an aqueous layer known as the Stern layer.

The Stern layer constitutes the inner part of the electrical double layer. It contains

the regularly spaced charged head groups and 60-90% of the counterions (the

bound counterions). The head groups are hydrated by a number of water

molecules. One or more methylene groups attached to the head group may be wet.

The core and the Stern layer form the kinetic micelle. (iii) The outer layer is a

diffuse layer and contains the remaining counterions and is called the Gouy-

Chapman layer that extends further into aqueous phase. The thickness of this layer

is determined by the (effective) ionic strength of the solution.

Fig.1.5: Schematic representation of the regions of spherical micelle.

Counterions binds a considerable amount to ionic micelles, which can be

evaluated by electrochemical measurement. They are bound to micelles primarily

not only by strong electrical field created by head groups, but also by specific

interactions that depend upon head group and counterion type [4, 51, 58]. A two-

site model has been successfully applied to the distributions of counterions; i.e.,

they are assumed to be either “bound” to the micellar pseudophase or “free” in the

aqueous phase [59-61]. The head group and counterion concentrations in the

interfacial region of an ionic micelle are on the order of 3-5 M, which gives the

micellar surface some of the properties of concentrated salt solutions [61-63].

Although the solution as a whole is electrically neutral, both the micellar and

aqueous pseudophases carry a net charge because thermal forces distribute a

fraction of the counterions radially into the aqueous phase [60, 61].

For non-ionic micelles the structure is essentially the same, except that the

outer region contains no counterions. It arrests water molecules at the palisade

layer (which includes the head groups and first few methylene groups) by

hydrogen bonding of the water with polyethylene oxide groups [64]. Water may

remain trapped in this region.

Reverse micelle

Aggregation of monomers can occur when amphiphiles are dissolved in

non-polar organic solvents. In reversed micelles the hydrocarbon tails are oriented

outward into the bulk solvent while the hydrophilic head groups are oriented

inward. Reverse micelle is more complex than normal micelles but can be used to

solubilize polar solutes in non-polar solvents. Dipole-dipole [65, 66] interactions

hold the hydrophilic head groups together in the core. The water molecules are

strongly associated with the head groups of surfactant. The aggregation properties

of surfactants in non-polar media are often altered markedly by the presence of

traces of water or additives. The size and properties of reverse micelles vary with

amount of water present [67-70]. Water in reverse micelles is expected to behave

very differently from ordinary water because of extensive binding and orientation

effects induced by polar heads forming the water core [71]. The inner cavity of

reverse micelles has been compared with active site of enzymes [69, 70]. Enzymes

have been encapsulated inside the water pool of reverse micelles without affecting

their activity. In recent years, the field of reverse micelles has witnessed a

significant growth of interest, partly due to the finding that proteins, other

biopolymers, and even bacterial cell can be solubilized in the reverse micellar

system: in fact, this has permitted the extension of area of interest to new domains,

i.e., biocatalysis and chemical biotechnology.

Mixed micelle

The formation of micelles from more than one chemical species gives rise

to what are known as mixed micelles. As usually used, however, the mixed

micelles means a micelle composed of amphiphiles capable themselves of forming

micelles. Thus mixed micellization is a special case of solubilization. The physico-

chemical properties of mixed micelles are quite different from those of pure

micelles of individual components. From the application point of view, mixed

micelles are of great importance in biological, technological, pharmaceutical and

medicinal formulation, enhanced oil recovery process for the purpose of

solubilization, suspension, dispersion, etc. [72]. Clint [73] developed analytical

description which contained both micelle composition and monomer concentration

above the mixed cmc for mixtures of non-ionic surfactants. Clint‟s treatment

assumed ideal mixing in the micelle. The properties of mixtures of ionic and non-

ionic amphiphiles [74-76] have been interpreted with the aid of the mixed micelle

formation. It was pointed out that the cmc of mixed surfactants was lower than

either of the single surfactants [73, 77].

Mixed micelles may also form when low molecular weight solutes are

solubilized by micelles of amphiphiles containing a relatively larger non-polar side

chain. The solubilized substances, also called as the penetrating additives [78],

may be located in both the hydrocarbon core [79] and in the hydrophilic mantle

[80-82].

Aggregation number

One of the most fundamental parameters defining a micelle is the

aggregation number (N), which provides direct information about the general size

and shape of aggregates formed by amphiphiles in the solution, and how these

properties are related to the molecular structure of amphiphile. The average

number of monomers in a micelle in a given population distribution or simply the

numbers of monomers making up a micelles, is known as the aggregation number

and is typically 30-200 in water. It is affected by the different factors such as

nature of amphiphile, temperature [2, 83-85], type and concentration of added

electrolyte [83, 86-88], organic additives [89-92], etc. Generally, in aqueous

medium greater the dissimilarity between amphiphile and solvent, the greater the

aggregation number. Hence, aggregation number appears to increase with increase

in hydrophobic character of the amphiphile. An increase in the temperature

appears to cause a small decrease in the aggregation number in aqueous medium

of ionics. For non-ionic surfactants, it increases markedly [93-95].

Micellar aggregation number decreases continuously with increase in

pressure for non-ionic surfactants [96, 97], although the number for ionic

surfactants passes through a minimum at around 1000 atm. Aggregation number of

ionic micelles is reported to increase [98-101] by the addition of electrolytes.

Various experimental techniques, like dynamic light scattering (DLS),

small angle neutron scattering (SANS), steady-state fluorescence quenching

(SSFQ), time-resolved fluorescence quenching (TRFQ), etc., have been used for

determination of the aggregation number [102-109].

Molecular shape

The extent of interaction between water and amphiphilic molecules can be

expressed by molecular shape and it is mainly determined by a balance between

hydrophobic interactions of the hydrocarbon tails, electrostatic repulsion and

hydration of head groups [14]. The shape of micelle produced in aqueous media

determines various amphiphilic solution properties such as, viscosity,

solubilization, and cloud point. Amphiphiles, which form spherical micelles in

water, have a conical shape in this aggregate type. Cylindrically formed molecules

have a polar region that is equal to non-polar, whereas wedge-shaped molecules

have a large non-polar region thus forming, for example, reversed micelles.

Substances with one hydrocarbon chain often belong to the conical group whereas

substances with two chains or one chain with unsaturations, giving kinks, belong

to cylinders and wedges.

A theory of micellar structure, based upon the geometry of various micellar

shapes and space occupied by the hydrophilic and hydrophobic groups of the

amphiphile molecules, has been developed by Israelachvilli, Mitchell, and Ninham

[110, 111]. The volume VH occupied by the hydrophobic groups in the micellar

core, the length of hydrophobic group in the core lc, and the cross-sectional area a0

occupied by the hydrophilic group at the micelle-solution interface are used to

calculate a packing parameter (Rp), which determines the shape of the micelle

Rp = VH / a0lc (1.1)

The optimal cross-sectional area per amphiphile molecule is observed

experimentally by X-ray diffraction of bilayer systems while the volume and

length of hydrocarbon tail may be calculated by Tanford [112] equations:

VH = (27.4 + 26.9 n) Å3 (1.2)

lc = (1.5 + 1.26 n) Å (1.3)

(n is the number of carbon atoms in the hydrocarbon chain).

As shown in Table 1.1, spherical micelles are formed when Rp is lower than

1/3; wormlike micelles are formed when Rp has a value in between 1/3 to 1/2;

vesicles or bilayers are formed when 1/2 < Rp < 1. When the volume of the

hydrocarbon part is large relative to the head group area (Rp > 1), reverse micelles

are formed.

Table 1.1: Aggregate structures with their corresponding packing parameters.

Effective shape of the

surfactant molecule

Packing parameter

(Rp)

Type of aggregation

cone

<1/3

spherical micelles

truncated cone

1/3–1/2

wormlike micelles

cylinder

1/2–1

bilayers

vesicles

inverted cone

>1

reverse micelles

However, it is to be noted that the solution parameters such as

concentration, pH, temperature and solvent polarity may heavily modify the

specific structures formed.

Factors affecting the value of critical micelle concentration

Since the properties of solutions of amphiphiles change markedly when

micelle formation commences, a great deal of work has been done on elucidating

the various factors that determine the concentration at which micelle formation

becomes significant (i.e., cmc), especially in aqueous media.

Among the factors known to effect the cmc markedly in aqueous solutions

are: (i) structure of amphiphiles, (ii) presence of various additives in the solution,

(iii) experimental conditions such as temperature, pressure, pH, solvent, etc.

(i) Structure of amphiphiles

(a) The hydrophobic group: The large majority of amphiphiles, whether

ionic or non-ionic have hydrophobic regions composed of hydrocarbon chains. For

ionic amphiphiles, increase in the number of carbon atoms in the unbranched

hydrocarbon chains leads to a decrease in the cmc. A generally used rule for

amphiphiles is that the cmc is halved by the addition of one methylene group to a

straight chain hydrophobic group attached to a single terminal hydrophilic group.

The presence of branched chains or double bond hinders micelle formation and

thus increases the cmc. When the number of carbon atoms in a straight-chain

hydrophobic group exceeds 16, however, the cmc no longer decreases so rapidly

with increase in the length of the chain and when the chain exceeds 18 carbon

atoms it may remain substantially unchanged with further increase in the chain

length. This may be due to the coiling of these long chains in water [14]. A phenyl

group that is a part of a hydrophobic group with terminal hydrophilic group is

equivalent to about three and one-half methylene groups. The replacement of

hydrocarbon-based hydrophobic group by a fluorocarbon-based one with the same

number of carbon atoms appears to cause a decrease in cmc. This is explained in

term of the enhanced hydrophobicity.

(b) The hydrophilic group: There is pronounced difference between the

cmcs of ionic and non-ionic surfactants with identical hydrophobic moieties. The

lower cmcs of non-ionic surfactants are a consequence of the lack of electrical

work necessary in forming the micelles.

Effect of nature of polar group of ionic surfactants on the micellar

properties has been reported by Anacker and coworkers and they concluded that

an important factor controlling the micellar size was mean distance of closest

approach of a counterion to the charge center of the surfactant [113]. Thus, for

example, decylammonium bromide forms very much larger micelles than

decyltrimethylammonium bromide because the Br- counterions are able to

approach more closely the charged nitrogen atom of decylammonium thus

effectively shielding the repulsive electrical forces and allowing larger micelle to

form. The more charged groups in the surfactants, the higher the cmc due to

increased electrical work required to form micelles [114, 115]. Zwitterionics

appear to have about the same cmc as ionics with the same number of carbon

atoms in the hydrophobic group. As the hydrophilic group is moved from the

terminal position to a more central position, however, the cmc increases. It is

because the hydrophobic group seems to act as if it had become branched at the

position of the hydrophilic group.

(ii) Presence of various additives in the solution

(a) Effect of electrolytes: Addition of electrolyte causes a reduction in the

thickness of the ionic atmosphere surrounding the polar head groups and a

consequent decreased repulsion between head groups of ionic micelles. These

effects are manifest as a reduction in cmc and an increase in aggregation number,

the effect being more pronounced for anionic and cationic than for zwitterionic

surfactants, and more pronounced for zwitterionics than for non-ionics. The effect

of the concentration of electrolyte on the cmc of ionics is given by the following

relation

log cmc = a log c1 + b (1.4)

where a and b are constants for a particular ionic group and c1 denotes the total

counterion concentration in molar unit [116].

For non-ionics and zwitterionics, Eq. (1.4) does not hold. Instead, the effect

is given by equation [117]

log cmc = – k c1 + constant (c1 < 1) (1.5)

where k is the constant for a particular surfactant, electrolyte and temperature and

c1 is concentration of electrolyte.

The size of counterion is also a determining factor for the cmc value. As the

size of counterion increases, counterion binding also increases due to decrease in

hydrated radius of ion, and hence decrease in cmc occurs [14]. This is the reason

why N)HC( 473 is more efficient in reducing the cmc than N)HC( 452 , which is

more efficient than N)(CH 43 .

There have been attempts to examine the salts effect on micelle formation

in the light of Hofmeister (lyotropic) series [118, 119]. The series plays a notable

role in a wide range of biological and physico-chemical phenomena. The change

in cmc of non-ionics and zwitterionics on the addition of electrolyte has been

attributed [120, 121] mainly to salting-out or salting-in (i.e., the effects of ion size

and decrease in dielectric constant) of the hydrophobic groups in the aqueous

solvent by the electrolyte, rather than to effect of the latter on the hydrophilic

groups of the amphiphile. Electrolytes capable of salting-out reduce the cmc of

non-ionic surfactants while salting-in electrolytes increase the cmc. The effect of

anion and cation in the electrolyte is additive and appear to depend on the radius

of the hydrated ion, that is, the lyotropic number; the smaller the radius of the

hydrated ion, the greater the effect. A very recent study carried out by Moulik and

coworkers [122] shows that, for a given anionic surfactant, the order of

effectiveness in reducing the cmc decreases in the order: 2Mg > Cs > K >

4NH > Na > Li . For a given non-ionic surfactant, the effect of anions on the

cmc follows the order: F > Cl > 2

4SO > Br > 3

4PO > 3

353 O(COO)HC > I >

SCN , and the effect of cations follows the order: K > Na > Rb > Li > 2Ca >

3Al [123].

(b) Effect of organic additives: Organic materials may produce marked

changes in the cmc in aqueous media, even if it is present in small amount. Since

some of these materials may be present as impurities or byproducts of the

amphiphiles, their presence may alter the properties of amphiphiles. A knowledge

of the effects of organic materials on the cmc of amphiphiles is therefore of great

importance for both theoretical and practical purposes. The main factor which

causes a decrease in cmc is likely to be the reduction of the free energy of the

micelle due to diluted surface charge density on micelle.

Organic compounds affect the cmc either by penetrating into the micellar

region, or by modifying solvent-micelle or solvent-monomer interactions. Both

increase and decrease of cmc are observed on addition of non-electrolytes like

urea, amides, amino acids, esters, carbohydrates, alcohols, etc. [124-131].

Methanol and ethanol cause a cmc increase, the higher alcohols butanol and

pentanol cause a decrease in this property. Propanol exhibits an intermediate

effect, low concentrations causing a decrease in cmc, higher concentrations (> 1

M) causing an increase. The cmc increasing effect of the lower alcohols has been

attributed to a weakening of the hydrophobic bonding. The cmc decreasing effects

are thought to be a consequence of the penetration of the alcohols into the palisade

layer of micelle, forming a mixed micelle.

Compounds that affect the cmc by modifying solvent-micelle or solvent-

surfactant interactions do so by modifying the structure of the water, its dielectric

constant, or its solubility parameter (cohesive energy density). Water structure

breakers like urea, formamide, and guinidinium salts are believed to increase the

cmc of surfactants in aqueous solutions (the increase of cmc of ionics by urea is

small), because of their disruption of water structure. Materials that promote water

structure such as xylose or fructose decrease the cmc of surfactants [132].

(iii) Effect of experimental conditions

(a) Temperature: The cmc value at a particular temperature is affected by

two different ways: (i) dehydration of hydrophilic group and (ii) disruption of

structured water around the hydrophobic group. Dehydration of hydrophilic part

favors the micellization while disruption of structured water around the

hydrophobic part disfavors the micellization. The relative magnitude of these two

opposing effects, therefore, determines whether the cmc increases or decreases

over a particular temperature range.

The micellization of amphiphile (ionic or non-ionic) is affected by

temperature due to change in interactions between hydrophobic tails and polar

head groups. cmc vs. temperature studies have been performed to obtain

information on these interactions [133]. For ionic systems, cmc first decreases to a

minimum value with temperature and then increases showing a U-shaped behavior

[134, 135]. However, in some cases continuous increase in cmc is observed with

increasing temperature [136, 137]. For non-ionic systems, cmc decreases

continuously with an increase in temperature due to an increase in the

hydrophobicity caused by destruction of hydrogen bonds between water molecules

and hydrophilic group [94]. From the data available, the minimum in the cmc-

temperature curve appears to be around 25 C for ionics [134] and around 50 C

for non-ionics [138, 139]. Data on the effect of temperature on zwitterionics are

limited. They appear to indicate a steady decrease in the cmc of alkylbetains with

increase in the temperature in the range of 6–60 C [140, 141].

(b) Effect of pressure: The effect of pressure on micelle formation of ionic

[142] and non-ionic surfactants [143] has been studied. The cmc increases upto

pressure of about 1000 atmosphere and decreases with further increase of pressure.

It has been suggested that the surfactant molecules when present in the micelle are

in a more expanded condition than when present as the monomer in solution, so

that the initial effects of pressure tend to compress the micelle and mitigate against

the increased freedom of the monomer in the micelle, thus giving a rise in cmc.

The decrease in cmc on increasing the pressure above 1000 atmospheres may be

due to an increase in the dielectric constant of water, making less electrical work

necessary to bring the monomer into a micelle. For non-ionic amphiphiles, the

cmc values increase monotonously and then level off with increasing pressure.

(c) Effect of pH: When amphiphile molecules contain ionizable groups such

as –NH2, –(CH3)2NO and –COOH, the degree of dissociation of the polar group

will be dependent on pH [144]. In general, the cmc will be high at pH values

where the group is charged (low pH for –NH2 and –(CH3)2NO, high pH for

-COOH) and low when uncharged. Some zwitterionic surfactants become cationic

at low pH, a change that can be accompanied by a rapid rise in the cmc [145], or a

more modest rise [146], depending on the structure and hence hydrophilicity of the

zwitterionic form.

(d) Solvent medium: In ethylene glycol, the cmc of surfactants decrease as

the length of the hydrophobic chain increases, but the change is much smaller than

that in water [147]. For polyoxyethylenated non-ionic solutions in benzene and

carbon tetrachloride, cmc decreases with increase in the length of the

polyoxyethylene group at constant hydrophobic chain length.

The cmc in benzene for alkylammonium carboxylates increases with

increase in the length of the alkyl chain of the anion but decreases with increase in

the length of the alkyl chain of the cation; in carbon tetrachloride, there is no

significant change in the value of the cmc with these structural changes. The cmc

is lower in D2O than H2O for different amphiphiles [148, 149]. The hydrophobic

bonds are expected to be stronger in D2O than H2O [150]. Also, micelles in D2O

are larger than H2O [151].

Thermodynamics of micellization

The process of micellization is one of the most important characteristics of

surfactant solution from theoretical as well as practical purposes and hence it is

essential to understand its mechanism (the driving force for micelle formation).

This requires analysis of the dynamics of the process (i.e., the kinetic aspects) as

well as the equilibrium aspects whereby the laws of thermodynamics may be

applied to obtain the free energy, enthalpy and entropy of micellization.

Two general approaches have been employed to tackle micelle formation.

The first and simplest approach treats micelles as a single phase, and is referred to

as the phase separation model [152-154]. Here, micelle formation is considered as

a phase separation phenomenon and the cmc is then the saturation concentration of

the amphiphile in the monomeric state whereas the micelles constitute the

separated pseudophase. Above the cmc, phase equilibrium exists with a constant

activity of the surfactant in the micellar phase. The Krafft point is viewed as the

temperature at which solid hydrated surfactant, micelles and a solution saturated

with undissociated surfactant molecules are in equilibrium at a given pressure. In

the second approach, micelles and single surfactant molecules or ions are

considered to be in association–dissociation equilibrium. In its simplest form, a

single equilibrium constant is used to treat the process. The cmc is merely a

concentration range above which any added surfactant appears in solution in a

micellar form. Since the solubility of the associated surfactant is much greater than

that of the monomeric surfactant, the solubility of the surfactant as a whole will

not increase markedly with temperature until it reaches the cmc region. Thus, in

the mass action [155-157] approach, the Krafft point represents the temperature at

which the surfactant solubility equals the cmc.

(1) The phase separation model

According to this model, micelles and counterions are treated as separate

phase. However, the micelles do not constitute a “phase” according to the true

definition of this concept since they are not homogeneous and uniform throughout.

Similarly, there are problems associated with the application of the phase rule

[158] while considering micelles as separate phase.

(i) Application of the phase separation model to non-ionic surfactants

To evaluate the thermodynamic parameters for the process of micellization

a primary requisite is to define the standard state. The hypothetical standard state

for the surfactant in the aqueous phase is taken to be the solvated monomer at unit

mole fraction with the properties of the infinitely dilute solution. For the surfactant

in the micellar state, the micellar state itself is considered to be the standard state.

If µs and µm are the chemical potentials per mole of the unassociated surfactant in

the aqueous phase and associated surfactant in the micellar phase, respectively,

then since these two phases are in equilibrium

µs = µm (1.6)

For non-ionized amphiphile,

µs = µ0

s + RT ln as (1.7)

where µ0

s is the chemical potential of standard state.

Since the micellar state is in its standard state

µm = µ0

m (1.8)

At low concentration of free monomers, the activity as is replaced by mole fraction

Xs.

If the 0

mΔG is the standard free energy for the transfer of one mole of

amphiphile from the solution to micellar phase, then

0

mΔG = µ0

m – µ0

s = µm – (µs – RT lnXs) = RT lnXs (1.9)

Assuming that the concentration of free surfactant in the presence of micelle is

constant and equal to the cmc value, Xcmc, then

0

mΔG = RT lnXcmc (1.10)

Xcmc is the cmc expressed as a mole fraction, therefore,

Xcmc = ns /(ns + nH2O) (1.11)

Since the number of moles of free surfactant, ns, is small compared to number of

moles of water, nH2O, therefore, Eq. (1.11) can be written as

Xcmc = ns /nH2O (1.12)

Substituting Eq. (1.12) into Eq. (1.10) and applying logarithm we get

0

mΔG = 2.303RT (logcmc – logw) (1.13)

where w = 55.40 M at 20 C.

Application of Gibbs–Helmholtz equation to Eq. (1.10) gives

∂/∂T( 0

mΔG /T)p = – R(∂lnXcmc /∂T)P = 0

mΔH /T2 (1.14)

Hence the standard enthalpy of micellization per mole of monomer, 0

mΔH , is

0

mΔH = – RT2 (∂lnXcmc /∂T)P = R (∂ lnXcmc /∂(1/T))P (1.15)

Also, standard entropy of micellization per mole of monomer, 0

mSΔ , is given by

0

mSΔ = ( 0

mΔH – 0

mΔG ) /T (1.16)

(ii) Application of phase separation model to ionic surfactants

Consider an anionic surfactant, in which n surfactant anions, S–, and n

counter ions M+ associate to form a micelle, i.e.,

nS– + nM

+ Sn

The micelle is simply a charged aggregate of surfactant ions plus an equivalent

number of counterions in the surrounding atmosphere and is treated as a separate

phase.

In the calculation of 0

mΔG , it is necessary to consider the transfer of (1 – g)

moles of counterions from its standard state to micellar state in addition to transfer

of surfactant molecules from the aqueous phase (g is degree of dissociation).

Therefore, Eq. (1.9) can be written as

0

mΔG = RT lnXs + (1 – g) RT lnXx (1.17)

where Xs and Xx are the mole fractions of surfactant ions and counterions,

respectively.

The analogous equations to Eqs. (1.10) and (1.13) for an ionic surfactant in the

absence of added electrolyte are

0

mΔG = (2 – g) RT lnXcmc (1.18)

0

mΔG = (2 – g) 2.303RT (logcmc – logw) (1.19)

It is assumed that micellar phase is composed of the charged aggregates together

with an equivalent number of counterions, and Eqs. (1.18) and (1.19) are

approximated to

0

mΔG = 2RT lnXcmc (1.20)

and

0

mΔG = 4.606RT (logcmc – logw) (1.21)

The enthalpy of micellization, 0

mΔH , for ionic surfactants is given by

0

mΔH = – 2 RT2

(∂ln Xcmc /∂T)P (1.22)

The phase separation model has been questioned for two main reasons. Firstly,

according to this model a clear discontinuity in the physical property of a

surfactant solution, such as surface tension, turbidity, etc., should be observed at

the cmc. This is not always found experimentally and the cmc is not a sharp break

point. Secondly, if two phases actually exist at the cmc, then equating the chemical

potential of the surfactant molecule in the two phases would imply that the activity

of the surfactant in the aqueous phase would be constant above the cmc. If this

was the case, the surface tension of a surfactant solution should remain constant

above the cmc. However, careful measurements have shown that the surface

tension of a surfactant solution decreases slowly above the cmc, particularly when

using purified surfactants.

(2) The mass-action model

This model assumes dissociation-association equilibrium between

surfactant monomers and micelles–thus equilibrium constant can be calculated.

The mass-action model was originally applied to ionic surfactants but latter it was

applied to non-ionic surfactants also.

(i) Application of the mass-action model to non-ionic surfactants

Micelles, M, are considered to be formed by a single step reaction from n

monomers, D, according to

nD M (1.23)

The equilibrium constant for micelle formation, Km, is then given by

Km = am/ (as)n (1.24)

Corkill et al. [159] have shown that at the cmc the standard free energy of

micellization, 0

mΔG , is given by

0

mΔG = RT [(1–1/ n) lnXcmc + f(n)] (1.25)

where

f(n) = 1/ n [ln n2(2n–1/ n –2) + (n –1) ln n(2n –1)/ 2(n

2 –1)] (1.26)

If n is large, Eq. (1.25) reduces to

0

mΔG = RT lnXcmc (1.27)

Applying the Gibbs–Helmohltz equation and assuming the aggregation number, n,

to be large and independent of temperature

0

mΔH = – RT2 (∂lnXcmc /∂T)P = R (∂lnXcmc /∂(1/T))P (1.28)

The aggregation numbers of many non-ionic surfactants vary with temperature and

in some cases a concentration dependence of n has been reported. In such cases

Eq. (1.28) is not applicable.

(ii) Application of mass-action model to ionic surfactants

The ionic micelles, M+p

, is considered to be formed by the association of n

surfactant ions, A+, and (n – p) firmly bound counterions, X

–

nD+ + (n – p) X

– M

+p (1.29)

The equilibrium constant for micelle formation assuming ideality, is thus,

Km = Xm/ (Xs)n (Xx)

n–p (1.30)

where Xx is the mole fraction of counterion.

The standard free energy of micellization per mole of monomeric surfactant is

given by

0

mΔG = – RT/ n lnKm = – RT/ n lnXm/ (Xs)n (Xx)

n-p (1.31)

When n is large, and when data in the region of the cmc are considered, Eq. (1.31)

becomes

0

mΔG = (2 – p /n) RT lnXcmc (1.32)

Eq. (1.32) is of the same form as Eq. (1.18) from the phase-separation model,

since g = p /n. The two equations differ slightly because of differences in the way

in which the mole fractions are calculated. In the phase-separation model the total

number of moles present at the cmc is equal to the sum of the moles of water and

surfactant whereas the total number of moles in the mass-action model is equal to

the sum of the moles of water, surfactant ions, micelles, and free counterions.

The standard enthalpy of micellization (per mole of monomer) is given by

0

mΔH = – (2 – g) RT2 (∂lnXcmc /∂T)P

= (2 – g) R [(∂lnXcmc/∂(1/T)]P (1.33)

The mass action model is more realistic model than the phase separation

model in describing the variation of monomer concentration with total

concentration above cmc. However, it suffers a serious limitation in that it

considers monodispersity of micelle size inspite of polydispersity. The phase

separation model assumes constant surfactant activity and hence surface tension

above cmc although neither of them remains constant. If aggregation number n is

infinite then mass action and phase separation models are equivalent.

Both the mass action and phase separation models, despite their limitations,

are useful representations of the micellar process and may be used to derive

equations relating the cmc to the various factors that determine it. Neither mass

action nor phase separation models are enough to explain the thermodynamics of

micellization completely. From the practical point of view a comprehensive

approach was developed, known as multiple equilibrium model [160], which

corrects the flaws of mass action model. The thermodynamic parameters are

determined either by calorimetry or by measuring cmc at different temperatures

but the results don‟t agree well. So it is clear from the above discussion that more

reliable data are necessary to overcome the present difficulties in the quantitative

interpretation of micellization and also should be aware of limitations and analyze

findings in terms of appropriate models.

Nevertheless, because of the simplicity of its application, the pseudophase

model is widely used to model thermodynamic data, particularly for long chain

surfactants having low cmc values. The mass action model allows for modeling of

thermodynamic properties over a broader concentration range, i.e., premicellar

range as opposed to the pseudo-phase model, which is applicable only in the post-

micellar range. As well, prediction of aggregation numbers can be made from the

mass action model, and it has been more successfully applied to short chain

surfactants.

(3) Other thermodynamic models

The thermodynamics of small systems developed by Hill [161] has been

applied to non-ionized, non-interacting surfactant systems by Hall and Pethica

[162]. In this approach, aggregation number is treated as thermodynamic variable,

thereby enabling variations in the thermodynamic functions of micelle formation

with the mean aggregation number, <n>, to be examined. The thermodynamic

functions of micellization, assuming solution ideality, are as under

0

mΔG = RT [lnX s– (lnXm /<n>)] (1.34)

0

mΔH = – RT2 [(dlnXs /dT)P – 1/ <n>(dlnXm /dT)P] (1.35)

0

mSΔ = – RT (dlnXs /dT)P + RT/ <n>(dlnXm /dT)P – R lnXs + (R/ <n>)lnXm (1.36)

For systems where <n> is large and changes little with temperature, Eqs.

(1.34) to (1.36) are reduced to the corresponding equations of mass-action or

phase-separation models.

Another approach for that of small systems was formulated by Corkill and

coworkers and applied to systems of non-ionic surfactants [163, 164]. This

multiple equilibrium model considers equilibria between all micellar species

present in solution rather than a single micellar species, as was considered by

mass-action theory. The standard free energy and enthalpy of micellization are

given by equations of similar form to equations (1.32) and (1.33) and are shown to

approximate satisfactorily to the appropriate mass-action equations for systems in

which the mean aggregation number exceeds 20.

An interesting model of micelle formation based on geometrical

considerations of micelle shape has been proposed by Tanford [165]. Equations

are presented which relate the micelle size and cmc to a size-dependent free

energy of micellization. The calculations are based on the assumptions of an

ellipsoidal shape. The hydrophobic component of the free energy is estimated in

terms of the area of contact between the hydrophobic core and the solvent. The

hydrophilic component of 0

mΔG , i.e., the free energy of repulsion between the head

groups, is assumed to be inversely proportional to the surface area per head group.

This approach has been further developed by Ruckenstein and Nagarajan [166]

and used in the prediction of the properties of sodium octanoate micellar solutions

[167].

Drugs and Their Classification

The term drug is derived from French word „Drogue‟ which means a dry

herb. A very broad definition of a drug would include „all chemicals other than

food that affect living processes‟. If the affect helps the body, the drug is a

medicine. However, if a drug causes a harmful effect on the body, the drug is a

poison. The same chemical can be a medicine and a poison depending on

conditions of use and the person using it.

Another definition would be “medicinal agents used for diagnosis,

prevention, treatment of symptoms, and cure of diseases”. Contraceptives would

be outside of this definition unless pregnancy was considered a disease.

It is to be noted that drugs are to be used for the benefit of recipient and it is

presumed that this refers to total benefit–physical, mental as well as economical.

Drugs are regarded as biologically active chemical compounds mostly with

a therapeutic purpose which can be broadly classified according to various criteria

including chemical structure or pharmacological action into:

(A) Biological classification

(B) Chemical classification

(C) Classification of drugs according to commercial consideration

(D) Classification by the lay public

(A) Biological classification

Biological classification is based on pharmacotherapeutic and

chemotherapeutic agent, i.e., this is as disease oriented classification of medicinal

agents used in various diseases and hence this classification is based on medicinal

agents which are overall descriptive but not very accurate on scientific grounds.

The broad classification based on gross overall biological effects is as follows:

(a) Drugs acting on central nervous system and peripheral nervous

systems: The central nervous system (CNS) which consists of brain and spinal

cord, and controls and regularizes the special functions like circulation, digestion

and respiration and it also modifies the psychic reactions such as feeling, attitude,

thoughts, and memory. It directs the functions of all tissues of the body. Chemical

influences are capable of producing a myriad of effects on the activity and

function of the central nervous system. Stimulants are drugs that exert their action

through excitation of the central nervous system. Psychic stimulants include

caffeine, cocaine, and various amphetamines. These drugs are used to enhance

mental alertness and reduce drowsiness and fatigue. However, increasing the

dosage of caffeine above 200 mg (about 2 cups of coffee) does not increase mental

performance but may increase nervousness, irritability, tremors, and headache.

(b) Chemotherapeutic drugs: Chemotherapy, in its most general sense, is

the treatment of disease by chemicals especially by killing micro-organisms or

cancerous cells. Various drugs used in chemotherapy are known as

chemotherapeutic drugs, which have important therapeutic use in the treatment of

parasitic infections due to insects, worms, protozoa, viruses, bacteria, etc. These

drugs destroy offending parasites or organisms without damaging the host tissues.

First modern chemotherapeutic agent was Paul Ehrlich's arsphenamine, an arsenic

compound discovered in 1909 and used to treat syphilis. This was later followed

by sulfonamides discovered by Domagk and penicillin discovered by Alexander

Fleming. Most commonly, chemotherapy acts by killing cells that divide rapidly,

one of the main properties of most cancer cells. This means that it also harms cells

that divide rapidly under normal circumstances: cells in the bone marrow,

digestive tract and hair follicles.

(c) Pharmacodynamic agents: These drugs affect the normal processes of

the body like blood circulation, hemodynamic process, i.e., blood pressure, cardiac

outputs, etc. Phamacodynamic agents include mainly the drugs which affect the

heart and blood circulation. It also includes a wide variety of the drugs used in

allergic and gastrointestinal diseases.

(d) Metabolic diseases and endocrine function: It includes variety of drugs

which are not conveniently classified in the other groups, like:

(i) Antirheumatic and autoimmuno disease drugs: Diseases modifying

antirheumatic drugs are the focus of treatment that addresses constant pain and

inflammations of the lung, heart and eye and autoimmune diseases arise from an

overactive immune response of the body against substances and tissues normally

present in the body. In other words, the body actually attacks its own cells. The

treatment of autoimmune diseases is typically with immunosuppression-

medication which decreases the immune response.

(ii) Dermatologicals: Dermatology is the branch of medicine dealing with

the skin and its diseases, a unique specialty with both medical and surgical

aspects. A dermatologist takes care of diseases, in the widest sense, and some

cosmetic problems of the skin, scalp, hair, and nails.

(iii) Anti-inflammatory drugs: Anti-inflammatory drugs are drugs with

analgesic and antipyretic (fever-reducing) effects and which have, in higher doses,

anti-inflammatory effects (reducing inflammation). The most prominent members

of this group of drugs are aspirin, ibuprofen, and naproxen.

(B) Chemical classification

Chemical classification is based on their chemical structure. According to

this classification drugs may come under one or more of these categories such as

quinines, semicarbazides, phenols, lactones, azo compounds, amides, alcohols,

acetals, ketones, hydrocarbons, halogenated compounds, guanides, enols, esters,

etc.

The implication of this classification is that similar chemical structure

should yield similar biological activities. Thus, structurally close analogous

compounds are grouped together with some overall activity but sometimes this

classification is not very accurate as a few compounds with similar structure lack

the activity test. Chemical structural classification of drugs is of advantage for

study of methodology and structure-activity relationship.

(C) Classification of drugs according to commercial consideration

The manufacturers and distributors of therapeutic agents classify the drugs

according to their operational expenses, research investment and profit margins.

Medicines for relatively rare diseases are called orphan drugs and such drugs lack

patient protection as production costs are high and demand is less.

Another classification of commercial consideration depends on the way of

administration of drug, i.e., drugs are given orally, parenterally (meaning

introduced subcutaneously, intravenously or by any route other than by way of the

digestive tract) by inhalation, sublingually, rectally, etc. On the whole, orally

active drugs are preferred by physicians and patients.

(D) Classification by the lay public

The few broad public classification depends upon the action of the drug, for

example, antiseptic and disinfectant, anthelmintics, expectorants, cough mixtures,

laxative and purgative, analgesics, tonics, ointments for skin diseases, etc., but this

classification is scientifically inadequate and public should be well informed about

all aspects of chemistry, biological action and fate of medicinal agent by

experimental biologists and medicinal chemists.

Many pharmacologically active compounds are amphiphilic or hydrophobic

molecules, which may undergo different kinds of association, and whose site of

action in the organism frequently is the plasma membrane. Even if their target is

intracellular, the interaction with this first barrier plays a fundamental role [168].

Classes of amphiphilic drugs include phenothiazine [169-175] and

benzodiazepine [176] tranquillizers [177-179], analgesics [179], peptide [180] and

nonpeptide [182, 183], antibiotics [183, 184], tricyclic antidepressants [185-188],

antihistamines [189], anticholinergics [190], -blockers [191], local anesthetics

(LA) [192-195], non-steroidal anti-inflammatory drugs [196], anticancer drugs

[197], etc. Many of these drugs contain one ore more (condensed or not) aromatic

nuclei, while others are of peptide nature. A great deal of data on the surface

active properties of the amphiphilic drugs can be found in the book by Attwood

and Florence [198] and other reviews [199-201].

Surface active drugs of quite different chemical structure are reported to

self-associate and bind to membranes, causing disruption and solubilization, in a

surfactant-like manner [168]. Depending on the kind of drug, the self-association

of these drugs is classified into two modes: micellar and nonmicellar aggregations.

Here the micellar aggregation means a single multimer (micelle) forms above the

cmc, and nonmicellar (stepwise) aggregation means that i-mer is successively

formed by aggregation of (i-1)-mer and monomer [198].

Mode of drug action

It is important to distinguish between actions of drugs and their effects.

Actions of drugs are the biochemical physiological mechanisms by which the

chemical produces a response in living organisms. The effect is the observable

consequence of a drug action. For example, the action of penicillin is to interfere

with cell wall synthesis in bacteria and the effect is the death of the bacteria.

One major problem of pharmacology is that no drug produces a single

effect. The primary effect is the desired therapeutic effect. Secondary effects are

all other effects beside the desired effect which may be either beneficial or

harmful. Drugs are chosen to exploit differences between normal metabolic

processes and any abnormalities which may be present. Since the differences may

not be very great, drugs may be nonspecific in action and alter normal functions as

well as the undesirable ones. This leads to undesirable side effects.

The biological effects observed after a drug has been administered are the

result of an interaction between that chemical and some part of the organism.

Mechanisms of drug action can be viewed from different perspectives, namely, the

site of action and the general nature of the drug-cell interaction.

Sites of drug action

(i) Enzyme inhibition

Drugs act within the cell by modifying normal biochemical reactions.

Enzyme inhibition may be reversible or non-reversible; competitive or non-

competitive. Antimetabolites may be used which mimic natural metabolites. Gene

functions may be suppressed.

(ii) Drug-receptor interaction

Drugs act on the cell membrane by physical and/or chemical interactions.

This is usually through specific drug receptor sites known to be located on the

membrane. A receptor is the specific chemical constituent of the cell with which a

drug interacts to produce its pharmacological effects. Some receptor sites have

been identified with specific parts of proteins and nucleic acids. In most cases, the

chemical nature of the receptor site remains obscure.

(iii) Non-specific interactions

Drugs act exclusively by physical means outside of cells. These sites

include external surfaces of skin and gastrointestinal tract. Drugs also act outside

of cell membranes by chemical interactions. Neutralization of stomach acid by

antacids is a good example.

Theories of Mixed Micellization

A mixed micelle consists of surfactant molecules of more than one type.

Interest in mixed micelles has largely been driven by industry, in search of

properties that may improve the performance of surfactant systems. Such a

synergistic effect greatly improves many technological applications in areas such

as emulsion formulations, interfacial tension reduction, cosmetic products,

pharmaceuticals, and petroleum recovery, etc. A synergistic interaction display

between the components of a mixture makes its physico-chemical properties better

than individual formulation. Many theoretical models have been put forward for

dealing with the mixed binary system to evaluate the composition and interaction

parameter among the components at the air/water interface and in the micellar

phase.

The first model given by Lange [77, 202] and used by Clint [73], is based

on phase separation model that relates the mole fraction and the critical micellar

concentration (cmc) of the component in an ideal mixture, which is applicable to

systems of mixed surfactants of similar structure, but hardly applicable to

dissimilar combinations. This model is an idealization which neglects the

interaction among different surfactants in the aggregated state. Rubingh [203] and

Rosen [204, 205] have made an attempt to explain the composition and specific

interaction parameters between two surfactants of nonideal mixture in the bulk and

in the interface, on the basis of regular solution theory (RST). The Rubingh model

treats the mixed micelles as a regular solution. Though these theories are

satisfactory but are questioned on thermodynamic grounds [206-208]. Motomura

[209] considered the mixed micelles as a macroscopic bulk phase and proposed his

thermodynamic model to describe the mixed micellar properties as a function of

excess thermodynamic quantities, defined with reference to the spherical dividing

surface. This model is independent of nature of surfactants and their counterions

and is suitable for prediction of micellar composition. Maeda [210] explained that

a mixed ionic-nonionic surfactant system often has a lower cmc much lower than

the cmc of the pure components. This can be attributed to the decrease in the ionic

head group repulsion caused by the presence of non-ionic surfactant molecules

between the head groups. Maeda suggested that besides regular solution

interaction parameter, there could be another parameter that actually contributes to

the stability of mixed micelles and put forward an equation to calculate the

thermodynamic stability of ionic-nonionic mixed micelle through free energy of

micellization function of micellar mole fraction of ionic components in the mixed

micelles. By the introduction of values of interaction parameter and micellar mole

fraction from different models, thermodynamic stability of mixed micelles can be

evaluated.

Georgiev‟s model is based on Markov‟s chain model [211] for

polymerization process of mixed micelles, and has introduced two molecular

parameters instead of one as in RST. Blankschtein [212, 213] has

thermodynamically formulated models for mixed-surfactant systems (nonideal

mixtures) to evaluate various physico-chemical parameters. This is based on the

cmc, chemical structure of hydrophobic and hydrophilic moieties of individual

components, surfactant concentration, temperature, salt effect, etc. This theory

helps to find out the cmc of binary surfactant mixtures, size and shape of the

micelles and phase behavior of solutions.

Molecular thermodynamic theory has a quantitative basis than RST, and

can be extended to multicomponent systems, expected to work better to know

exact information on a mixed surfactant system [213].

Clouding Phenomenon in Aqueous Solutions

The cloud point (CP) of a fluid is the temperature at which dissolved solids

are no longer completely soluble, precipitating as a second phase giving the fluid a

cloudy appearance [214]. This term is relevant to several applications with

different consequences. Phase separation results from the competition between

entropy, which favors miscibility of micelles in water, and enthalpy, which favors

separation of micelles from water [215, 216]. Depending on the variation of these

two contributions with temperature, either a lower or an upper consolute point can

result [215, 216].

Binary liquid mixtures that display partial miscibility exhibit critical

solution temperatures (CST) or consolute temperatures. CST‟s are of two kinds:

upper critical solution temperature (UCST), above which the liquid pair is

completely miscible and below which phase separation occurs, and lower critical

solution temperature (LCST), below which the two components are completely

miscible while above it the two components become partially miscible and form

two separate phases. The appearance of LCST is a rather rare phenomenon for

solutions of small molecules but is more frequent when at least one of the

molecules is large. The importance of the entropy of mixing, which favors mixing,

becomes relatively less important when the molecules get larger and the mixing

process becomes more dominated by the enthalpy term, which may favor or

disfavor mixing.

If the solution is cold, a temperature below which the amphiphile is not

really very soluble (Fig.1.6) at all is reached, known as the Krafft temperature

[217-220]. If, on the other hand, the temperature is raised, especially for non-ionic

amphiphiles or those with some non-ionic polar groups, a two-phase region is

encountered, above what is known as the CP [221-223] where two liquid

(micellar) phases are in equilibrium. Finally, if we increase concentrations at

ambient temperature, one starts to encounter, usually at amphiphile concentrations

above 40 % by weight, a series of mesomorphic phases sometimes called liquid

crystalline phases.

Cloudy micellaremulsion (2-phase)

Micelles Liquid crytals (mesophases)

Crystals

T

0 100Concentration (%)

Fig.1.6: Schematic temperature (T)–concentration phase diagram illustrating the

types of amphiphilic aggregates encountered by moving away from the micellar

region.

One may find from the literature that there are two classes of surfactants

and the temperature effect on the solution behaviors of each class are in sharp

contrast. The first class is the non-ionic surfactants, the micellar size of which

increases (or at least does not decrease) with increase in temperature. Such

systems always have cloud point properties [19, 224-232]. This behavior has been

attributed to dehydration of the hydrophilic group of the surfactant with increasing

temperature [227]. The absence of long range electrostatic interactions between

aggregates and the decreasing hydration of non-ionic head groups with increasing

temperature result in spontaneous phase separation.

The ionic surfactants belong to the second class in which the cloud point

phenomenon is rarely observed [228]. Until recently it was thought that this type

of behavior was not possible in binary ionic surfactant-water solutions due to large

electrostatic repulsions between the aggregates.

The clouding behavior of amphiphiles is strongly affected by the presence

of various additives in the solution either by changing the structural properties of

the micelles by solubilization in the micellar aggregates or by dissolving in water

phase and thus changing the environment of the micelles [229-234].

The mechanism of CP has not been exactly known and has been discussed

from two view points. One is that the aggregation number of the micelles increases

and intermicellar repulsions decrease with the increase in temperature [14, 235].

As the temperature increases, micellar growth and increased intermicellar

attraction cause the formation of particles, e.g., rod like micelles that are so large

that the solution becomes visibly turbid [236]. Turbidity measurements [224, 237-

239] have been performed in order to determine the micellar size. However, this

interpretation has been criticized [240, 241] because the turbidity must show a big

increase owing to the presence of CP, a phenomenon that has nothing to do with

an increase in the molecular weight of the micelles.

Other methods used to determine the micellar size [239, 242, 243], e.g.

diffusion, viscosity and sedimentation measurements and osmometry, have, in

general, confirmed that the micelles are small at low temperatures but larger at

higher ones. However, these methods are also subject to difficulties in

distinguishing between molecular weight and intermicellar interactions.

Corti et al. [222] explained the behavior as critical fluctuation. The

interpretation is that as the CP is approached the micelles come together, and

above the CP they separate out as second phase. They were able to evaluate the

critical exponents from the light scattering data. The existence of attractive

interactions between poly(oxyethylene) alkyl ethers at elevated temperatures has

been demonstrated convincingly by Claesson et al. [244]. Lindman [245] has

advanced a model based on conformational changes in the poly(oxyethylene)

chain with changing temperature, from which a change in the dipole moment of

the hydrophilic chain arises. This, in turn, leads to a decrease in the polarity or

hydrophilicity of the surfactant and, hence, to phase separation. Kjellender [246,

247] has argued persuasively that attractions between spherical micelles cannot

give rise to the low observed critical concentrations but are a consequence of

attraction between anisotropic micelles.

High concentration of salts can cause ionic surfactant solutions to separate

into immiscible surfactant-rich and surfactant-poor phases [19]. This phenomenon

has been investigated since the 1940s and was first observed for mixtures of the

cationic surfactant Hyamine 1622 with salts such as potassium thiocynate (KSCN)

and potassium chloride (KCl) [248, 249]. The phase separation is typically of the

upper consolute type, i.e., it occurs on cooling below a characteristic temperature,

which, in turn, increases with salt content. Later on, few more studies on ionic

surfactant-salt combinations were performed to show CP phenomenon (lower

consolute type) [250, 251]. Appell and Porte [228] found cloud points at high

concentrations of sodium chlorate (NaClO3) in aqueous solutions of either

cetyltrimetylammonium bromide (CTAB) or cetylpyridinium bromide (CPB). In a

later study Warr et al. [250] showed that quaternary ammonium surfactants with

tributyl head groups exhibit cloud points in binary aqueous solution. Adding salt

to these surfactant solutions lowers the cloud point temperature. They [250]

advanced a mechanism involving hydration shells to account for cloud points,

whereas Appell and Porte [228] interpreted the clouding of CPB/NaClO3 mixtures

as being analogous to the phase separation of polymers in a poor solvent.

Recently, Raghavan et al. [252] has reported the clouding behavior in ionic

amphiphiles in presence of salts with hydrophobic counterions. The plausible

hypothesis given is that the binding of hydrophobic counterions promotes micellar

branching. As free micellar ends are incorporated into a branched network, the

viscosity of the solution drops, and the entropic attraction between junction

eventually causes phase separation. Interest has been focussed on the possibility

that upper or lower critical points could occur within ordered liquid crystal phases.

An upper consolute loop within a lamellar phase has been reported for binary

anionic [253] or cationic [254] surfactants in water. However, lower consolute

loops are much rarer. Some ionic surfactants are reported [250] to undergo phase

separation without the addition of electrolyte, and their micelles remain spherical

or near spherical throughout their region of stability. The parameters, which

govern the phase equilibria and particularly the lower consolute behavior of ionic

surfactant solutions, have been detailed [251].

According to Yu and Xu [255], there may be four factors responsible for

the CP phenomenon in ionic amphiphiles: van der Waals attraction, electrical

repulsion, solvation layer and hydrophobic interactions. They proposed a

mechanism for clouding in tetrabutyltetradecyl sulfate. They postulated that butyl

chains belonging to TBA+ associated with one micelle could cross-link to another

micelle helping overcome the effects of electrostatic repulsion and an energetic

barrier due to oriented water near the surfaces of the two micelles. To be operative

geometrically, it appears that the two micelles would have to approach one another

intimately due to the limited extent of short butyl chains.

Zana et al. [256-259] opposed the mechanism for clouding in TBADS [or

SDS + TBA+] which explains that reducing the water hydrating the micelles is

responsible for CP. The hypothesis is supported by the fact that alkylammonium

counterions are quite bulkyl and ought to expel water from the palisade layer in

the same way that bulky head groups do [260]. Measurements of the water content

of the palisade layer will be needed to confirm the expectation [261]. If indeed

clouding is induced somehow by dehydrating the micelle surface, then the

interpretation of the data will be further complicated by presence of Na+ because

increasing the aggregation number of globular micelle leads to less water per

surfactant [259, 261]. This is a consequence of fact that the surface area of a

micelle grows more slowly than its volume, leading to a smaller volume per

surfactant in which to fit the water [259, 261]. Adding Na+ increases the

aggregation number of SDS. Therefore, there would be two competing

mechanisms to dehydrate: one displacement of water by the counterions and

another by the geometric constrictions due to micelle growth. Therefore, one

would need to know the details of the micelle aggregation numbers in the presence

of both TBA+ and Na

+ to gain a clear understanding.

To the previously suggested mechanisms for clouding in ionic micelles,

they suggested [256] that a second layer of TBA+ is loosely attached outside the

polar shell of the TBADS micelle because steric restrictions did not appear to

allow enough available volume to house a sufficient number of counterions. If this

second layer is in fact available, the cross-linking between micelles could take

place between butyl groups of the TBA+ ions in the second layer This possibility is

supported by the tendency of TBA+ ions to self-associate [262-265].

Recently, Kim and Shah [266-268] have observed the CP phenomenon in

amphiphilic drug amitriptyline hydrochloride solutions and have explored the

effect of additives. Also, Kabir-ud-Din and his group [269-271] have studied CP

phenomenon in some amphiphilic drug solutions and examined the effects of

different additives.

Relevance of the Research Problem

Although the pharmacological activity of the amphiphilic drugs appears at

low concentration where aggregation is negligible [201], the accumulation of drug

can occur at certain site of organism after long period of administration, giving

rise to formation of aggregates that are unable to pass through membranes;

decreasing transport rate and consequently leading to adverse effect on health.

Thus, the study of physico-chemical properties of amphiphilic drugs is important

from physical, chemical, biological and pharmaceutical point of view for their

implication. As most of the drugs that we have so far considered form micelles at

concentrations which they do not attain in vivo, it is most likely that it is their

surface-active characteristics which are most important biologically, although the

propensity of the molecules to form associations by hydrophobic bonding will

manifest itself. The study of the properties of surface active drugs in solution

provides an opportunity to investigate the influence of the structure of the

hydrophobe on the mode of association of amphiphiles.

A most common challenge faced by pharmaceutical scientists as well as

industry is to design and develop drugs with good aqueous solubility while

simultaneously retaining potency and selectivity [272]. The absorption properties

(which cause also bioavailability) of these compounds are influenced by their

physico-chemical and biological properties. A number of methodologies have

been adopted to improve the aqueous solubility (and hence bioavailability) of

drugs. This problem can be overpowered by the use of mixed micelles of drug–

surfactant or surfactant–surfactant. Drug delivery systems which have attracted

much attention for their potential to improve the pharmacological properties of the

drug include nanocapsules [273], cell ghost [274], liposomes [275] and micelles

[272, 276].

Micellar solubilization is the most convenient method to increase the

solubility of drugs. A mixed amphiphile system can exhibit surface and colloidal

properties different from those of the pure individual components. Nonideal

mixing of amphiphilic components often causes synergism in the properties of the

mixtures that may be exploited in their applications. When a mixed amphiphile

system shows lower critical micelle concentration (cmc) values than that of pure

components, the system is said to be synergistic. As a result, mixed micelles are

commonly used in pharmaceutical formulations, in industries, and in enhanced oil

recovery processes [72, 277, 278].

Nowadays, gemini surfactants [26] are gaining wide attention due to their

superior properties. These surfactants contain two hydrophobic tails and two

hydrophilic heads joined with a spacer (of variable nature) at the level of head

groups. These surfactants have cmc values 10–100 times lower than conventional

surfactants.

Keeping the above in view and the fact that surfactant micelles, like many

other amphiphilic substances, are potentially important encapsulating/solubilizing

agents, we have performed conductometric measurements on some amphiphilic

drug-surfactant mixed systems.

The solution properties of amphiphiles are sensitive to the presence of

additives. The values of cmc are found to depend on the type and nature of

additives. To optimize the applications of amphiphile mixtures, it is, therefore,

important to understand the interplay of forces that govern the micellization

behavior in the presence of additives. It was shown by Mouritsen and Jorgensen

[279] and Tieleman et al. [280] that amphiphilic drugs insert into membranes as

interstitial components and they affect the organization of lipids. As the electrolyte

concentration in the membranes may vary, their presence and concentration may

affect the micellization tendency of the drug. Therefore, it is important to have

knowledge of drug‟s association behavior with temperature and also when present

with electrolytes.

In order to understand the effect of additives on the micellar properties of

amphiphilic drugs, we have, therefore, determined the cmc in presence of

inorganic salts and urea/thiourea as well as with the change in temperature by

conductometric method.

The amphiphilic drugs, because of their surfactant-like nature, exhibit

concentration, temperature and pH-dependent phase separation [254-256]. It was

observed that cloud point (CP) can vary with additives. When using these drugs it

should be kept in mind that normal body temperature is typically 12 degrees above

ambient. Even if the CP of pure drug in buffer is above this temperature, it may

decrease in presence of additives, especially surfactants which are used as drug-

carrier. As clouding concentrates the drug in a small volume, it may affect the

activity of drugs and, therefore, it is important to have knowledge of clouding

behavior of the drugs in designing more effective drug-carrier combinations. With

this idea in mind, effects of various additives, viz., electrolytes, non-electrolytes,

alcohols, surfactants, sugars, and amino acids have been examined on CP behavior

of some amphiphilic drugs.

Layout of the Thesis

This thesis consists of five chapters including this one which is concerned

mainly with the general introduction of amphiphiles. Experimental details are

provided in Chapter II.

Chapter III presents a detailed and systematic study of micellar properties

of two antidepressants (AMT and IMP) and a phenothiazine (PMT) drugs in

presence of surfactants (conventional and gemini) in aqueous media. Surfactants

are generally used as drug carriers in pharmaceuticals but presence of surfactants

may alter the micellization tendency of a drug as surfactants form mixed micelles

with the drug: this may affect the activity of the drug. Therefore, it is important to

have knowledge of the effect of surfactants on micelle formation of drugs and the

related energetics.

Chapter IV presents the effect of additives (salts and ureas) on the

association behavior of the above mentioned drugs. Electrolytes and urea are

found in the body and study of their effect on micellization will allow the better

designing of effective therapeutic agents.

Studies on the effect of various additives on the CP values of the above

mentioned drugs are described in Chapter V.

References:

[1] M. J. Lawrence, Chem. Soc. Rev., 23, 1994, 417.

[2] J. N. Israelachvilli, Intermolecular and Surface Forces, Academic Press,

London, 1991.

[3] W. C. Griffin, J. Soc. Cosmet. Chem., 1, 1949, 311.

[4] J. H. Fendler, Membrane Mimetic Chemistry, Wiley-Interscience, New York,

1982.

[5] G. J. T. Tiddy, A. Khan, Curr. Opin. Colloid Interface Sci., 4, 1999, 379.

[6] S. Lang, Curr. Opin. Colloid Interface Sci., 7, 2002, 12.

[7] P. Mukerjee, in: Physical Chemistry: Enriching Topics from Colloid and

Surface Science, H. van Olphen, K. J. Mysels (Eds.), Theorex, La Jolla, CA,

1975.

[8] M. J. Rosen, Surfactants and Interfacial Phenomena, 3rd

ed., John Wiley &

Sons, New Jersey, 2004.

[9] S. A. Baeurle, J. Kroener, Math. Chem., 36, 2004, 409.

[10] D. Myers, Surfactant Science and Technology, 3rd

ed., VCH Publishers, New

Jersey, 2005.

[11] Y. Moroi, Micelles, Theoretical and Applied Aspects, Plenum Press, New

York, 1992.

[12] R. Zana, in: Structure-Performance Relationship in Surfactants, K. Esumi, M.

Ueno (Eds.), 2nd

ed., Marcel Dekker, New York, 2003.

[13] K. R. Lange, in: Surfactants: A Practical Handbook, K. R. Lange (Ed.),

Hanser Publishers, Munich, 1999.

[14] M. Hellsten, in: Industrial Applications of Surfactants, D. R. Karsa (Ed.), The

Royal Society of Chemistry, London, 1987.

[15] D. W. Deamer, R. M. Pashley, Origins Life Evol. Biosphere, 19, 1989, 21.

[16] T. L. Metcalfe, P. J. Dillon, C. D. Metcalfe, Environ. Toxicol. Chem., 27,

2008, 811.

[17] E. Emmanuel, K. Hanna, C. Bazin, G. Keck, B. Clément, Y. Perrodin,

Environment International, 31, 2005, 399.

[18] M. G. Murphy, M. Al-Khalidi, J. F. Crocker, S. H. Lee, P. O'Regan, P. D.

Acott, Chemosphere, 59, 2005, 235.

[19] Cationic Surfactants, E. Jungermann (Ed.), Marcel Dekker, New York, 1970.

[20] Cationic Surfactants: Physical Chemistry, D. N. Rubingh, P. M. Holland

(Eds.), Marcel Dekker, New York, 1991.

[21] Anionic Surfactants, W. M. Linfield (Ed.), Marcel Dekker, New York, 1967.

[22] Anionic Surfactants: Physical Chemistry of Surfactant Action, E. H. Lucassen-

Reynders (Ed.), Marcel Dekker, New York, 1981.

[23] S. De, V. K. Aswal, P. S. Goyal, S. Bhattacharya, J. Phys. Chem., 100, 1996,

11664.

[24] M. J. Rosen, D. J. Tracy, J. Surfact. Deterg., 1, 1998, 547.

[25] F. M. Menger, J. S. Keiper, Angew. Chem. Int. Ed., 39, 2000, 1906.

[26] Novel Surfactants, K. Holmberg (Ed.), Marcel Dekker, New York, 1998.

[27] C. A. Bunton, L. Robinson, J. Schaak, F. M. Stam, J. Org. Chem., 36, 1971,

2346.

[28] M. J. Rosen, CHEMTECH, 23, 1993, 30.

[29] F. M. Menger, A. V. Peresypkin, J. Am. Chem. Soc., 123, 2001, 5614.

[30] R. Zana, Adv. Colloid Interface Sci., 97, 2002, 205.

[31] F. Devinsky, I. Marasova, I. Lacko, J. Colloid Interface Sci., 105, 1985, 235.

[32] M. J. Rosen, Z. H. Zhu, X. Y. Hua, J. Am. Oil Chem. Soc., 30, 1992, 69.

[33] G. Paddon-Jones, S. Regismond, K. Kwetkat, R. Zana, J. Colloid Interface

Sci., 243, 2001, 496.

[34] V. E. Sevedynk, M. Alami, K. Nyden, K. Holmborg, A. V. Peresypkin, F. M.

Menger, Langmuir, 16, 2002, 206.

[35] M. J. L. Castro, J. Kovensky, A. F. Cirrelli, Langmuir, 18, 2002, 2477.

[36] M. A. Johnsson, M. C. A. Stuart, J. B. F. N. Engbert, Langmuir, 19, 2003,

4609.

[37] F. M. Menger, J. S. Keiper, V. Azov, Langmuir, 16, 2000, 2062.

[38] L. Perez, J. L. Torres, A. Manresa, C. Solans, M. R. Infante, Langmuir, 12,

1996, 5296.

[39] K. Sakai, S. Umezawa, M. Tamura, Y. Takamatsu, K. Tsuchiya, K. Torigoe,

T. Ohkubo, T. Yoshimura, K. Esumi, H. Sakai, M. Abe, J. Colloid Interface

Sci., 318, 2008, 440.

[40] F. M. Menger, S. Wrenn, J. Phys. Chem., 78, 1974, 1387.

[41] S. Agharkar, S. Lindenbaum, J. Phys. Chem., 79, 1975, 2068.

[42] R. Zana, in: Specialist Surfactants, I. D. Robb (Ed.), Blackie, Academic and

Professional, New York, 1997.

[43] W. C. Preston, J. Phys. Colloid Chem., 52, 1948, 84.

[44] P. Mukerjee, K. J. Mysels, Critical Micelle Concentrations of Aqueous

Surfactant Systems, Natl. Stand. Ref. Data. Ser. (U. S. Natl. Bur. Standands),

No. 36, 1971.

[45] L. J. Cline Love, J. G. Habarta, J. G. Dorsey, Anal. Chem., 56, 1984, 1132A.

[46] D. W. Armstrong, Sep. Purif. Methods, 14, 1985, 213.

[47] D. G. Davis, C. R. Bury, J. Chem. Soc., 1930, 2263.

[48] J. H. Fendler, E. J. Fendler, Catalysis in Micellar and Macromolecular

Systems, Academic Press, New York, 1975.

[49] K. Shinoda, T. Nakagawa, B. Tamamushi, T. Isemura, Colloid Surfactants:

Some Physico-Chemical Properties, E. Hutchinson, P. van Rysselberghe

(Eds.), Academic, New York, 1963.

[50] P. H. Elworthy, A. T. Florence, C. B. Macfarlane, Solubilization by Surface

Active Agents and its Applications in Chemistry and Biological Science,

Chapman and Hall, London, 1968.

[51] K. J. Mysels, Introduction to Colloid Chemistry, Wiley, New York, 1959.

[52] J. G. Dorsey, Adv. Chromatogr., 27, 1987, 167.

[53] W. Marcel, Proteins: Struct. Funct. Genet., 1, 1986, 4.

[54] E. H. Cordes, Pure and Appl. Chem., 50, 1978, 617.

[55] F. M. Menger, J. M. Jerkunica, J. C. Johnston, J. Am. Chem. Soc., 100, 1978,

4676.

[56] F. M. Menger, Acc. Chem. Res., 12, 1979, 111.

[57] J. M. Corkill, J. F. Goodman, T. Walker, Trans. Faraday Soc., 63, 1967, 768.

[58] P. Mukerjee, K. Mysels, P. Kapauan, J. Phys. Chem., 97, 1993, 2764.

[59] H. Gustavsson, B. Lindman, J. Am. Chem. Soc., 100, 1978, 4647.

[60] B. Lindman, H. Wennerstrom, Top. Curr. Chem., 87, 1980, 1.

[61] C. A. Bunton, F. Nome, F. H. Quina, L. S. Romsted, Acc. Chem. Res., 24,

1991, 357.

[62] D. Stigter, J. Phys. Chem., 68, 1964, 36.03.

[63] D. W. R. Gruen, Prog. Colloid Polym. Sci., 70, 1985, 6.

[64] S. P. Moulik, S. Gupta, A. R. Das, Can. J. Chem., 67, 1989, 356.

[65] M. Ueda, Z. A. Schelly, Langmuir, 4, 1988, 653.

[66] M. Bourrel, R. S. Schechter, Microemulsions and Related Systems, Marcel

Dekker, New York, 1991.

[67] G. W. Brady, M. Kaplan, J. Chem. Phys., 58, 1973, 3535.

[68] G. W. Brady, J. Chem. Phys., 58, 1973, 3542.

[69] Y. M. Tricot, D. N. Furlong, W. H. F. Sasse, Aust. J. Chem., 37, 1984, 1147.

[70] J. H. Fendler, Acc. Chem. Res., 13, 1980, 7.

[71] W. D. Weatherford, J. Dispersion Sci. Technol., 6, 1985, 467.

[72] R. M. Hill, in: Mixed Surfactant Systems, K. Ogino, M. Abe (Eds.), Marcel

Dekker, New York, 1993.

[73] J. H. Clint, J. Chem. Soc., Faraday Trans.1, 71, 1975, 1327.

[74] T. Nakagawa, H. Inoue, Bull. Chem. Soc. Jpn., 76, 1956, 104.

[75] J. M. Corkill, J. F. Goodman, J. R. Tate, Trans. Faraday Soc., 60, 1964, 986.

[76] D. N. Rubingh, T. Jones, Ind. Eng. Chem. Prod. Res. Dev., 21, 1982, 176.

[77] H. Lange, K. H. Beck, Kolloid Z. Z. Polym., 251, 1973, 424.

[78] M. F. Emerson, A. Holtzer, J. Phys. Chem., 89, 1985, 3320.

[79] P. Mukerjee, J. Pharm. Sci., 60, 1971, 1528.

[80] P. Mukerjee, J. Pharm. Sci., 60, 1971, 1531.

[81] Ch. D. Prasad, H. N. Singh, P. S. Goyal, K. S. Rao, J. Colloid Interface Sci.,

155, 1993, 415.

[82] P. M. Lindemuth, G. L. Bertrand, J. Phys. Chem., 97, 1993, 7769.

[83] C. Tanford, The Hydrophobic Effect, Formation of Micelles and Biological

Membranes, Wiley, New York, 1980.

[84] R. Zana. C. Weill, J. Phys. Lett., 46, 1985, L-953.

[85] W. Binana-Limbele, R. Zana, J. Colloid Interface Sci., 121, 1988, 81.

[86] N. A. Mazer, in: Dynamic Light Scattering, R. Pecora (Ed.), Plenum, London,

1991.

[87] P. J. Missel, N. A. Mazer, M. C. Carey, G. B. Benedeck, J. Phys. Chem., 93,

1989, 8354.

[88] R. Alargova, J. Petkov, D. Petsev, I. B. Ivanov, G. Broze, A. Mehreteab,

Langmuir, 11, 1995, 1530.

[89] S. Kumar, Kirti, Kabir-ud-Din, J. Am. Oil Chem. Soc., 71, 1994, 763.

[90] P. Lianos, J. Lang, C. Strazielle, R. Zana, J. Phys. Chem., 86, 1982, 1019.

[91] P. Lianos, J. Lang, R. Zana, J. Phys. Chem., 86, 1982, 4809.

[92] F. Grieser, J. Phys. Chem., 85, 1981, 928.

[93] A. Malliaris, J. L. Moigne, J. Sturm, R. Zana, J. Phys. Chem., 89, 1985, 2709.

[94] Nonionic Surfactants, M. J. Schick (Ed.), Marcel Dekker, New York, 1967.

[95] W. Brown, R. Johnson, P. Stilbs, B. Lindman, J. Phys. Chem., 87, 1983, 4548.

[96] N. Nishikido, M. Shinozaki, G. Sugihara, M. Tanaka, J. Colloid Interface Sci.,

82, 1981, 352.

[97] M. Okawauchi, M. Shinoazki, Y. Ikawa, M. Tanaka, J. Phys. Chem., 91, 1987,

109.

[98] S. Hayashi, S. Ikeda, J. Phys. Chem., 84, 1980, 744.

[99] S. Ikeda, S. Hayashi, T. Imae, J. Phys. Chem., 85, 1981, 106.

[100] J. -M. Chen, T. -M. Su, C. Y. Mou, J. Phys. Chem., 90, 1986, 2418.

[101] S. Kumar, V. K. Aswal, P. S. Goyal, Kabir-ud-Din, J. Chem. Soc., Faraday

Trans., 94, 1998, 761.

[102] B. L. Bales, M. Almgren, J. Phys. Chem., 99, 1995, 15153.

[103] R. G. Alargova, I. I. Kochijashky, M. L. Sierra, R. Zana, Langmuir, 14, 1998,

5412.

[104] R. Ranganathan, L. Tran, B. L. Bales, J. Phys. Chem. B, 104, 2000, 2260.

[105] E. Y. Sheu, S. -H. Chen, J. S. Huang, J. Phys. Chem., 91, 1987, 3306.

[106] Y. Moroi, R. -H. Baker, M. Gratzel, J. Colloid Interface Sci., 119, 1987, 588.

[107] R. R. Durand, S. M. Hajji, R. Coudert, J. Phys. Chem., 92, 1988, 1222.

[108] P. J. Tummino, A. Gafni, Biophys. J., 64, 1993, 1580.

[109] M. H. Gehlen, F. C. D. Schryver, J. Phys. Chem., 97, 1993, 11242.

[110] J. N. Israelachvilli, D. J. Mitchell, B. W. Ninham, J. Chem. Soc., Faraday

Trans.2, 72, 1976, 1525.

[111] D. J. Mitchell, B. W. Ninham, J. Chem. Soc., Faraday Trans.2, 77, 1981, 601.

[112] C. Tanford, J. Phys. Chem., 76, 1972, 3020.

[113] R. D. Geer, E. H. Eylar, E. W. Anacker, J. Phys. Chem., 75, 1971, 369.

[114] G. V. Hartland, F. Grieser, J. Chem. Soc., Faraday Trans.1, 83, 1987, 591.

[115] M. S. Bakshi, P. Kohli, Indian J. Chem., 36A, 1997, 1075.

[116] M. L. Corrin, W. D. Harkins, J. Am. Chem. Soc., 69, 1947, 684.

[117] A. Ray, G. Nemethy, J. Am. Chem. Soc., 93, 1971, 6787.

[118] F. Hofmeister, Arch. Exp. Pathol. Pharmacol., 24, 1888, 247.

[119] W. Kunz, J. Henle, B. W. Ninham, Curr. Opin. Colloid Interface Sci., 9, 2004,

19.

[120] P. Mukerjee, Adv. Colloid Interface Sci., 1, 1967, 242.

[121] A. Ray, Nature (London), 231, 1971, 313.

[122] K. Maiti, D. Mitra, S. Guha, S. P. Moulik, J. Mol. Liq., 146, 2009, 44.

[123] L. Zhang, P. Somasundaran, C. Maltesh, Langmuir, 12, 1996, 2371.

[124] H. N. Singh, S. Swarup, Bull. Chem. Soc. Jpn., 51, 1978, 1534.

[125] M. Abu-Hamdiyyah, L. Al-Mansour, J. Phys. Chem., 83, 1979, 2236.

[126] M. Almgren, S. Swarup, J. E. Loefroth, J. Phys. Chem., 89, 1985, 4621.

[127] H. Suzuki, Bull. Chem. Soc. Jpn., 49, 1970, 1470.

[128] M. S. Chauhan, G. Kumar, A. Kumar, S. Chauhan, Colloids Surf. A, 51, 2000,

166.

[129] C. C. Ruiz, Colloids Surf. A, 147, 1999, 349.

[130] W. B. Gratzer, G. H. Beaven, J. Phys. Chem., 73, 1969, 2270.

[131] M. S. Ramdan, D. F. Evans, R. Lumry, S. Phison, J. Phys. Chem., 89, 1985,

3404.

[132] M. J. Schwuger, Ber. Bunsen-Ges. Phys. Chem., 75, 1971, 167.

[133] D. P. Miller, L. J. Magid, D. F. Evans, J. Phys. Chem., 94, 1990, 5921.

[134] B. D. Flockhart, J. Colloid Interface Sci., 16, 1961, 484.

[135] J. A. Stead, H. J. Tayer. J. Colloid Interface Sci., 30, 1969, 482.

[136] Kabir-ud-Din, U. S. Siddiqui, S. Kumar, A. A. Dar, Colloid Polym. Sci., 284,

2006, 807.

[137] C. C. Ruiz, L. Diaz-Lopez, J. Aguiar, J. Colloid Interface Sci., 305, 2007, 293.

[138] E. H. Crook, D. B. Fordyce, G. F. Trebbi, J. Phys. Chem., 67, 1963, 1987.

[139] L. -J. Chen, S. -Y. Lin, C. -C. Huang, E. -M. Chen, Colloids Surf. A, 135,

1998, 175.

[140] K. Tori, T. Nakagawa, Kolloid Z. Z. Polym., 189, 1963, 50.

[141] M. Dahanayake, M. J. Rosen, ACS Symposium Series, 253, 1984, 49.

[142] M. Okawauchi, M. Shinoazki, Y. Ikawa, M. Tanakana, J. Phys. Chem., 91,

1987, 109.

[143] N. Nishikido, N. Yoshimura, M. Tanaka, S. Kaneshina, J. Colloid Interface

Sci., 78, 1980, 338.

[144] F. Tokiwa, Adv. Colloid Interface Sci., 3, 1972, 389.

[145] J. M. Corkill, K. W. Gemmell, J. F. Goodman, T. Walker, Trans. Faraday

Soc., 64, 1969, 1817.

[146] M. J. Rosen, B. Y. Zhu, ACS Symposium Series, 253, 1984, 61.

[147] A. Ray, J. Am. Chem. Soc., 91, 1969, 6511.

[148] P. Mukerjee, P. Kapauan, H. G. Meyer, J. Phys. Chem., 70, 1966, 783.

[149] M. F. Emerson, A. Holtzer, J. Phys. Chem., 71, 1967, 3320.

[150] G. C. Kresheck, H. Schneider, H. A. Scheraga, J. Phys. Chem., 69, 1965,

3132.

[151] N. J. Chang, E. W. Kaler, J. Phys. Chem., 89, 1985, 2996.

[152] K. Shinoda, Bull. Chem. Soc. Jpn., 26, 1953, 101.

[153] K. Z. Shinoda, E. Hutchinson, J. Phys. Chem., 66, 1962, 577.

[154] Y. Moroi, N. Nishikido, H. Uehara, R. Matuura, J. Colloid Interface Sci., 50,

1975, 254.

[155] R. C. Murray, G. S. Hartley, Trans. Faraday Soc., 31, 1935, 183.

[156] J. N. Philip, Trans. Faraday Soc., 51, 1955, 561.

[157] P. Mukerjee, J. Phys. Chem., 76, 1972, 565.

[158] B. A. Pethica, Proc. IIIrd Inter. Cong. Surface Activity Cologne, 1, 1960, 212.

[159] J. M. Corkill, J. F. Goodman, S. P. Harrold, Trans. Faraday Soc., 60, 1964,

202.

[160] D. Myers, Surfaces Interfaces and Colloids, Principles and Applications, 2nd

ed., Wiley-VCH, New York, 1999.

[161] T. L. Hill, Thermodynamics of Small Systems, vols. 1 and 2, Benjamin, New

York, 1963/1964.

[162] D. G. Hall, B. A. Pethica, Nonionic Surfactants, M. J. Schick (Ed.), Arnold,

London, 1967.

[163] J. M. Corkill, J. F. Goodman, T. Walker, J. Wyer, Proc. Roy. Soc. A, 312,

1969, 243.

[164] J. M. Corkill, J. F. Goodman, Adv. Colloid Interface Sci., 2, 1969, 297.

[165] C. Tanford, J. Phys. Chem., 78, 1974, 2469.

[166] E. Ruckenstein, R. Nagarajan, J. Chem. Soc., Faraday Trans.2, 79, 1975,

2622.

[167] F. Eriksson, J. C. Eriksson, Per Stenius, Solution Chemistry of Surfactants,

vol. 1, Plenum, New York, 1979.

[168] S. Schreier, S. V. P. Malheiros, E. de Paula, Biochim. Biophys. Acta, 1508,

2000, 210.

[169] D. Attwood, A. T. Florence, J. N. M. Gillian, J. Pharm. Sci., 63, 1974, 988.

[170] D. Attwood, R. Natarajan, J. Pharm. Pharmacol., 33, 1981, 136.

[171] A. D. Atherton, B. W. Barry, J. Colloid Interface Sci., 106, 1985, 479.

[172] E. Wajnberg, M. Tabak, P. A. Nussenzveig, C. M. Lopes, S. R. Louro,

Biochim. Biophys. Acta, 944, 1988, 185.

[173] D. Attwood, V. Mosquera, C. Rey, M. Garcia, J. Colloid Interface Sci., 147,

1991, 316.

[174] D. Attwood, V. Mosquera, J. L. Lopez-Fonton, M. Garcia, F. Sarmiento, J.

Colloid Interface Sci., 184, 1996, 658.

[175] M. Perez-Rodrigues, G. Prieto, C. Rega, L. M. Varela, F. Sarmiento, V.

Mosquera, Langmuir, 14, 1998, 4422.

[176] D. Attwood, R. Blundell, V. Mosquera, M. Garcia, J. Colloid Interface Sci.,

161, 1993, 19.

[177] P. Seeman, Pharmacol. Rev., 24, 1972, 583.

[178] M. Huang, J. W. Daly, J. Med. Chem., 15, 1972, 458.

[179] L. N. Domelsmith, L. L. Munchausen, K. N. Houk, J. Am. Chem. Soc., 99,

1977, 6506.

[180] D. Attwood, J. A. Tolley, J. Pharm. Pharmacol., 32, 1980, 761.

[181] P. M. Hwang, H. J. Vogel, Biochem. Cell Biol., 76, 1998, 235.

[182] P. Taboada, D. Attwood, J. M. Ruso, M. Garcia, F. Sarmiento, V. Mosquera,

J. Colloid Interface Sci., 216, 1999, 270.

[183] L. M. Varela, C. Rega, M. J. Suarez-Filloy, J. M. Ruso, G. Prieto, D. Attwood,

F. Sarmiento, V. Mosquera, Langmuir, 15, 1999, 6285.

[184] K. L. Rundlett, D. W. Armstrong, Anal. Chem., 67, 1995, 2088.

[185] S. D. Rychnovsky, B. N. Rogers, T. I. Richardson, Acc. Chem. Res., 31, 1998,

9.

[186] A. D. Atherton, B. W. Barry, J. Pharm. Pharmacol., 37, 1985, 854.

[187] D. Attwood, V. Mosquera, M. Garcia, M. J. Saurez, F. Sarmeinto, J. Colloid

Interface Sci., 175, 1995, 201.

[188] F. Sarmiento, J. L. Lopez-Fontan, G. Prieto, D. Attwood, V. Mosquera,

Colloid Polym. Sci., 275, 1997, 1144.

[189] D. Causon, J. Gettins, J. Gormally, R. Greenwood, N. Natarajan, E. Wyn-

Jones, J. Chem. Soc., Faraday Trans.2, 77, 1981, 143.

[190] S. Yokoyama, Y. Fujino, Y. Kawamoto, A. Kaneko, Chem. Pharm. Bull., 42,

1994, 1351.

[191] J. M. Ruso, D. Attwood, C. Rey, P. Taboada, V. Mosquera, F. Sarmiento, J.

Phys. Chem. B, 103, 1999, 7092.

[192] W. A. Frezzatti Jr., W. R. Toselli, S. Schreier, Biochim. Biophys. Acta, 860,

1986, 531.

[193] D. Attwood, P. Fletcher, J. Pharm. Pharmacol., 38, 1986, 494.

[194] M. Wakita, Y. Kuroda, Y. Fujiwara, T. Nakagawa, Chem. Phys. Lipids, 62,

1992, 45.

[195] H. Matsuki, S. Hashimoto, S. Kaneshina, M. Yamanaka, Langmuir, 10, 1994,

1882.

[196] T. Rades, C. C. Muller-Goymann, Int. J. Pharm., 159, 1997, 215.

[197] S. Y. King, A. M. Basista, G. Torosian, J. Pharm. Sci., 78, 1989, 95.

[198] D. Attwood, A. T. Florence, Surfactant Systems, Their Chemistry, Pharmacy

and Biology, Chapman and Hall, New York, 1983.

[199] A. Felmiester, J. Pharm. Sci., 61, 1972, 151.

[200] K. Thoma, K. Albert, Pharmazie, 38, 1983, 807.

[201] D. Attwood, Adv. Colloid Interface Sci., 55, 1995, 271.

[202] H. Lange, Kolloid Z., 131, 1953, 96.

[203] D. N. Rubingh, in: Solution Chemistry of Surfactants, K. L. Mittal (Ed.), vol.

1, Plenum Press, New York, 1979.

[204] Q. Zhou, M. J. Rosen, Langmuir, 19, 2003, 4555.

[205] L. Liu, M. J. Rosen, J. Colloid Interface Sci., 179, 1996, 454.

[206] M. J. Rosen, J. H. Mathias, L. Davenport, Langmuir, 15, 1999, 7340.

[207] N. J. Turro, P. L. Kuo, P. Somasundaran, K. Wang, J. Phys. Chem., 90, 1986,

288.

[208] M. J. Rosen, F. Zhao, J. Colloid Interface Sci., 95, 1983, 443.

[209] K. Motomura, M. Yamanaka, M. Aratono, Colloid Polym. Sci., 262, 1984,

948.

[210] H. Maeda, J. Colloid Interface Sci., 172, 1995, 98.

[211] G. S. Georgiev, Colloid Polym. Sci., 274, 1996, 49.

[212] C. Sarmoria, S. Puvvada, D. Blankschtein, Langmuir, 8, 1992, 2690.

[213] S. Puvvada, D. Blankschtein, J. Phys. Chem., 96, 1992, 5567.

[214] N. M. van Os, J. R. Haak, L. A. M. Rupert, Physico-Chemical Properties of

Selected Anionic, Cationic and Nonionic Surfactants, Elsevier, Amsterdam,

1993.

[215] D. Blankschtein, G. M. Thurston, G. B. Benedek, J. Chem. Phys., 85, 1986,

7268.

[216] C. L. Liu, Y. J. Nikas, D. Blankschtein, Biotechnol. Bioeng., 52, 1996, 185.

[217] F. Krafft, Ber. Deutch Chem. Gesell., 32, 1899, 1596.

[218] Y. Moroi, R. Matuura, Bull. Chem. Soc. Jpn., 61, 1988, 333.

[219] C. La Mesa, L. Coppola, Collloids Surf., 35, 1989, 325.

[220] H. Matsuki, R. Ichikawa, S. Kaneshina, H. Kamaya, I. Udeda, J. Colloid

Interface Sci., 181, 1996, 362.

[221] R. J. Robson, E. A. Dennis, J. Phys. Chem., 81, 1977, 1075.

[222] M. Corti, C. Minero, V. Degiorgio, J. Phys. Chem., 88, 1984, 309.

[223] K. H. Raney, H. L. Benson, J. Am. Oil Chem. Soc., 67, 1990, 722.

[224] R. R. Balambra, J. S. Clunie, J. M. Corkill, J. F. Goodman, Trans. Faraday

Soc., 60, 1964, 979.

[225] R. Triolo, L. J. Magid, J. S. Johnson, H. R. Child, J. Phys. Chem., 86, 1982,

3689.

[226] J. C. Ravey, J. Colloid Interface Sci., 94, 1983, 289.

[227] J. B. Hayter, M. Zulauf, Colloid Polym. Sci., 260, 1982, 1023.

[228] J. Appell, G. Porte, J. Phys. Lett., 44, 1983, L-689.

[229] A. S. Sadaghiania, A. Khan, J. Colloid Interface Sci., 144, 1991, 191.

[230] H. Schott, J. Colloid Interface Sci., 173, 1995, 265.

[231] L. Koshy, A. H. Saiyad, A. K. Rakshit, Colloid Polym. Sci., 274, 1996, 582.

[232] J. H. Qian, L. W. Zhu, R. Guo, J. Chim. Chem. Soc., 52, 2005, 1245.

[233] P. Yan, J. Huang, R. C. Lu, C. Jin, J. X. Xiao, Y. M. Chen, J. Phys. Chem. B,

109, 2005, 5237.

[234] J. -L. Li, D. -S. Bai, B. -H. Chen, Colloids Surf. A, 346, 2009, 237.

[235] G. J. T. Tiddy, Phys. Rep., 57, 1980, 1.

[236] O. Glatter, G. Fritz, H. Lindner, J. Brunner-Popela, R. Mittelbach, R. Strey, S.

U. Egelhaaf, Langmuir, 16, 2000, 8692.

[237] P. Becker, J. Colloid Sci., 16, 1961, 49.

[238] D. Attwood, J. Phys. Chem., 72, 1968, 339.

[239] J. M. Corkill, T. Walker, J. Colloid Interface Sci., 39, 1972, 621.

[240] K. W. Hermann, J. G. Brashmiller, W. L. Courchere, J. Phys. Chem., 70,

1966, 2409.

[241] M. Corti, V. Degiorgio, J. Phys. Chem., 85, 1981, 1442.

[242] C. Tanford, Y. Nozai, M. F. Rohde, J. Phys. Chem., 81, 1977, 1555.

[243] E. J. Staples, G. J. T. Tiddy, J. Chem. Soc., Faraday, Trans., 74, 1978, 2530.

[244] P. Claesson, R. Kjellander, P. Stenius, H. G. Christenson, J. Chem. Soc.,

Faraday Trans., 89, 1986, 2735.

[245] B. Lindman, A. Carlsson, G. Karlstrom, M. Malmsten, Adv. Colloid Interface

Sci., 32, 1990, 183.

[246] R. Kjellander, E. Florin, J. Chem. Soc., Faraday Trans.1, 77, 1981, 2053.

[247] R. Kjellander, J. Chem. Soc., Faraday Trans.2, 78, 1982, 2025.

[248] H. L. Booij, in: Colloid Science, H. R. Kruyt (Ed.), Elsevier, Amsterdam,

1949.

[249] I. Cohen, C. F. Hiskey, G. Oster, J. Colloid Sci., 9, 1954, 243.

[250] G. G. Warr, T. N. Zemb, M. Drifford, J. Phys. Chem., 94, 1990, 3086.

[251] S. A. Buckingham, C. J. Gravey, G. G. Warr, J. Phys. Chem., 97, 1993,

10236.

[252] S. R. Raghavan, H. Edland, E. W. Kaler, Langmuir, 18, 2002, 1056.

[253] J. Ockleford, B. A. Timini, K. S. Narayan, G. J. T. Tiddy, J. Phys. Chem., 97,

1993, 6767.

[254] T. Zemb, D. Gazeau, M. Dubois, T. Gulik-Krzywicki, Europhys. Lett., 21,

1993, 759.

[255] Z. -J. Yu, G. Xu, J. Phys. Chem., 93, 1989, 7441.

[256] M. Benrraou, B. L. Bales, R. Zana, J. Phys. Chem. B, 107, 2003, 13432.

[257] B. L. Bales, R. Zana, Langmuir, 20, 2004, 1579.

[258] B. L. Bales, R. Zana, J. Phys. Chem. B, 106, 2002, 1926.

[259] B. L. Bales, M. Benrraou, R. Zana, J. Phys. Chem. B, 106, 2002, 9033.

[260] B. L. Bales, A. M. Howe, A. R. Pitt, J. A. Roe, P. C. Griffiths, J. Phys. Chem.

B, 104, 2000, 264.

[261] B. L. Bales, L. Messina, A. Vidal, M. Peric, O. R. Nascimento, J. Phys. Chem.

B, 102, 1998, 10347.

[262] W. -Y. Wen, S. Saito, J. Phys. Chem., 68, 1964, 2639.

[263] M. J. Blandamer, M. J. Faster, N. J. Hidden, M. C. R. Symons, Trans.

Faraday Soc., 64, 1968, 3247.

[264] H. E. Wirth, A. Lo Surdo, J. Phys. Chem., 72, 1968, 751.

[265] A. Lo Surdo, H. E. Wirth, J. Phys. Chem., 76, 1972, 130.

[266] E. J. Kim, D. O. Shah, Langmuir, 18, 2002, 10105.

[267] E. J. Kim, D. O. Shah, Colloids Surf. A, 227, 2003, 105.

[268] E. J. Kim, D. O. Shah, J. Phys. Chem. B, 107, 2003, 8689.

[269] S. Kumar, Md. S. Alam, N. Parveen, Kabir-ud-Din, Colloid Polym. Sci., 284,

2006, 1459.

[270] Md. S. Alam, A. Z. Naqvi, Kabir-ud-Din, J. Colloid Interface Sci., 306, 2007,

161.

[271] Md. S. Alam, A. Z. Naqvi, Kabir-ud-Din, Colloid Polym. Sci., 285, 2007,

1573.

[272] A. N. Lukyanov, V. P. Torchilin, Adv. Drug Deliv. Res., 56, 2004, 1273.

[273] P. Couvreur, G. Barratt, E. Fattal, P. Legrand, C. Vauthier, Ther. Drug

Carrier Syst., 19, 2002, 99.

[274] K. Jalava, A. Hensel, M. Szostak, S. Resch, W. Lubitz, J. Control. Rel., 85,

2002, 17.

[275] V. P. Torchilin, Nat. Rev. Drug Discov., 4, 2005, 145.

[276] G. S. Kwon, Crit. Rev. Ther. Drug Carrier Syst., 20, 2003, 357.

[277] P. M. Holland, in: Mixed Surfactant Systems; P. M. Holland, D. N. Rubingh

(Eds.), ACS Symposium Series, American Chemical Society, Washington,

DC, 1992.

[278] S. Ghosh, S. P. Moulik, J. Colloid Interface Sci., 208, 1999, 357.

[279] O. G. Mouritsen, K. Jorgensen, Chem. Phys. Lipids, 73, 1994, 3.

[280] D. P. Tieleman, S. J. Marrink, H. J. C. Berendesen, Biochim. Biophys. Acta,

1331, 1997, 235.