1) SURFACTANTS

2) MICELLIZATION
3) SOLUBILIZATION
1
TERMINOLOGIES
Amphipathic : combining both natures (oil and
water)

Amphiphilic : with affinity for both (oil and

water). Such molecules are commonly termed
surfactants, OR surface-active agents.

Hydrophilic: with affinity for water

Lipophilic : with affinity for oil

Lyophilic : with affinity for the solvent

Lyophobic : lack of affinity for the solvent 2

TERMINOLOGIES
Krafft point:
Kraft point (kt) also known as critical micelle
temperature or Kraft temperature is the
minimum temperature at which the surfactant
form micelles irrespective of surfactant
concentration.
Cloud point:

Cloud point is the temperature above which some

surfactants begin to precipitate. The appearance
of turbidity at cloud point is due to separation of
solution into two phases.
3
 INTERFACE

Surface-active agents are organic

molecules that, when dissolved in a
solvent at low concentration, have the
ability to adsorb (or locate) at interfaces,
thereby altering significantly the physical
properties of those interfaces.

4
INTERFACE

The term interface is commonly employed

here to describe the boundary in liquid/liquid,
solid/liquid and gas/liquid systems, although in
the latter case the term surface can also be
used. This adsorption behavior can be attributed
to the solvent nature and to a chemical structure
for surfactants that combine both a polar and a
non-polar (amphiphilic) group into a single
molecule. To accommodate for their dual nature,
amphiphiles therefore sit at interfaces so that
their lyophobic moiety keeps away from strong
solvent interactions while the lyophilic part 5
remains in solution.
REDUCTION OF SURFACE AND
INTERFACIAL TENSION

When surfactants are dissolved in water they

orientate at the surface so that the hydrophobic
regions are removed from the aqueous
environment, as shown in Figure. The reason for
the reduction in the surface tension when
surfactant molecules adsorb at the water surface
is that the surfactant molecules replace some of
the water molecules in the surface and the forces
of attraction between surfactant and water
molecules are less than those between two water
molecules, which results in a tendency for the
surface to contract. 6
REDUCTION OF SURFACE AND
INTERFACIAL TENSION

Surfactants will also adsorb at the

interface between two immiscible liquids
such as water and oil and will orientate
themselves, with their hydrophilic group
in the water and their hydrophobic group
in the oil. The interfacial tension at this
interface, which arises because of a
similar imbalance of attractive forces as
at the water surface, will be reduced by
this adsorption.
7
REDUCTION OF SURFACE AND
INTERFACIAL TENSION

There is an equilibrium between

surfactant molecules at the surface of the
solution and those in the bulk of the
solution which is expressed by the Gibbs
equation

8
REDUCTION OF SURFACE AND
INTERFACIAL TENSION

The surface activity of a particular

surfactant depends on the balance
between its hydrophilic and hydrophobic
properties. For a homologous series of
surfactants:
An increase in the length of the
hydrocarbon chain (hydrophobic)
increases the surface activity. This
relationship between hydrocarbon chain
length and surface activity is 9
REDUCTION OF SURFACE AND
INTERFACIAL TENSION

expressed by Traubes rule, which states

that in dilute aqueous solutions of
surfactants belonging to any one
homologous series, the molar
concentrations required to produce equal
lowering of the surface tension of water
decreases threefold for each additional
CH2 group in the hydrocarbon chain of
the solute.
10
SURFACTANTS

Solutesor molecules that are

preferentially adsorbed at the surface or
interface of liquids reduce the surface or
interfacial tension and are therefore
termed as surface active agents or
surfactants
11
SURFACTANTS
Surfactants have two distinct regions in their
chemical structure, one of which is water-liking
or hydrophilic and the other of which is water-
hating or hydrophobic. These molecules are
referred to as amphiphilic or amphipathic
molecules or simply as surfactants or
surface active agents. The existence of two
such moieties in a molecule is referred to as
amphipathy and the molecules are consequently
often referred to as amphipathic molecules.

12
SURFACTANTS
These molecules form oriented monolayers
at interfaces and show surface activity
(i.e., they lower the surface or interfacial
tension of the medium in which they are
dissolved). In some usage surfactants are
defined as molecules capable of
associating to form micelles.

13
WHAT DOES SURFACTANT DO ?
SUBSTANCE WHICH REDUCES SURFACE/INTERFACIAL
TENSION BETWEEN TWO PHASES

Water & Oil

are mortal Surface
enemies Tension
Force
between
two liquids

Surfactants
acts as clamp
binding Water
& Oil are
together 14
TYPES OF SURFACTANT DEPENDING ON
THEIR IONIZATION IN AQUEOUS SOLUTIONS

Depending on their charge characteristics, surface-

active molecules may be
Anionic

Cationic

Non-ionic

Zwitterionic

(ampholytic).

15
CLASSIFICATION

ANIONIC SURFACTANTS
Amongst the different classes of surfactants,
anionics are often used in applications, mainly
because of the ease and low cost of manufacture
They contain negatively charged head group.

The most commonly encountered anionic

surfactants have carboxylate, sulfate,
sulfonate and phosphate polar groups in
combination with counterions such as sodium
and potassium (for water-solubility) or
calcium and magnesium (for oil-solubility).
16
CLASSIFICATION
Alkali soaps consist of the ammonium,
potassium and sodium salts of long chain
fatty acids such as oleic, steric and
ricinoleic acid. These are however
unstable below pH 10 and are
incompatible with long chain organic
cations. Example of this group of
surfactants are potassium and sodium
stearate.
17
CLASSIFICATION
Amine soaps
Metallic soaps Examples include
calcium and aluminium stearate.

18
CLASSIFICATION
Alkyl sulphates and phosphates are
the esters formed by reaction of fatty
alcohols with sulphuric acid and
phosphoric acid respectively. Examples
include sodium lauryl sulphate,
sodium cetostearyl sulphate and
triethanolamine lauryl sulphate.
Alkyl sulphonates include Disodium
sulfosuccinate and are effective wetting
agents 19
CLASSIFICATION
Sodium Lauryl Sulfate BP
is very soluble in water at room
temperature, and is used
pharmaceutically as a preoperative skin
cleaner, having bacteriostatic action
against Gram-positive bacteria, and also
in medicated shampoos
is a component of emulsifying wax. (fast
track)
20
CLASSIFICATION
CATIONIC SURFACTANTS
Cationics have positively charged head groups .
In the most common cationic surfactants the
charge is carried on a nitrogen atom as, for
example, with amine and quaternary ammonium
surfactants.
The quaternary ammonium and pyridinium
cationic surfactants are important
pharmaceutically because of their bactericidal
activity against a wide range of Gram-positive
and some Gram-negative organisms.
21
CLASSIFICATION
They may be used on the skin, especially
in the cleaning of wounds.
Their aqueous solutions are used for
cleaning contaminated utensils.
Following are generally negatively
charged (e.g., metal, plastics, minerals,
fibres, hairs and cell membranes) so that
they can be modified upon treatment with
cationic surfactants.
22
CLASSIFICATION
NON-IONIC SURFACTANTS

Most common non-ionic surfactants are those

with a poly(oxyethylene) chain as the hydrophilic
group.
Non-ionics contain groups with a strong affinity
for water due to strong dipole-dipole interactions
arising from hydrogen bonding, e.g., ethoxylates .
Sorbitan esters are supplied commercially as
Spans and are mixtures of the partial esters of
sorbitol and its mono- and di-anhydrides with
oleic acid. They are generally insoluble in water
(low hydrophilelipophile balance (HLB) value)
and are used as water-in-oil emulsifiers. 23
CLASSIFICATION
NON-IONIC SURFACTANTS
Polysorbates are complex mixtures of
partial esters of sorbitol and its mono-and
di-anhydrides condensed with an
approximate number of moles of ethylene
oxide. They are supplied commercially as
Tweens. The polysorbates are miscible
with water, as reflected in their higher
HLB values, and are used as emulsifying
agents for oil-in-water emulsions.
24
CLASSIFICATION
NON-IONIC SURFACTANTS
Poloxamers are synthetic block
copolymers of hydrophilic
poly(oxyethylene) and hydrophobic
poly(oxypropylene) . Properties such as
viscosity, HLB and physical state (liquid,
paste or solid) are dependent on the
relative chain lengths of the hydrophilic
and hydrophobic blocks. They are supplied
commercially as Pluronics
25
CLASSIFICATION

NON-IONIC SURFACTANTS
One advantage over ionics is that the length of
both the hydrophilic and hydrophobic groups can
be varied to obtain maximum efficiency in use.
They find applications in low temperature
detergents and emulsifiers.

26
CLASSIFICATION

ZWITTERIONIC AND AMPHOTERIC

SURFACTANTS

Zwitterionic and amphoteric surfactants

possess polar head groups which on
ionisation may impart both positive and
negative charges. The positive charge is
almost always carried by an ammonium
group and the negative charge is often a
carboxylate.
27
HYDROPHILIC-LIPOPHILIC BALANCE
(HLB)
Surfactants comprise of both polar and
non polar groups in their molecule.
Surfactants with more polar groups are
predominantly lipophilic.
The balance b/w the hydrophilic and
lipophilic nature of the surfactant may be
given by means of HLB system which
consists of an arbitrary scale of values
assigned to different surfactants based on
their nature. 28
HYDROPHILIC-LIPOPHILIC BALANCE
(HLB)
The HLB system was first introduced by
Griffin in 1949 for classification of non
ionic surfactants but has since been
applied to ionic surfactants as well.
In this system, each surfactant is assigned
a number b/w 1 and 20 representing the
relative proportions of lipophilic and
hydrophilic parts of the molecule.

29
HYDROPHILIC-LIPOPHILIC BALANCE
(HLB)
The higher the number, the more hydrophilic the
agent.
Depending on their HLB values, the surfactants
have different uses.
Surfactants with HLB values of between 3 and 6
are lipophilic and form w/o emulsions, while
values of 8 to 18 indicate predominantly
hydrophilic characteristics and the formation of
o/w emulsions.
The HLB values of a number of surfactants are
available in the literature
30
CLASSIFICATION ON THE BASIS OF
HYDROPHILIC-LIPOPHILIC BALANCE (HLB)
Anti-foaming agent (HLB=0-3)
Emulsifying agent w/o (HLB=4-6)

Wetting/spreading agent (HLB=7-9)

Emulsifying agent o/w (HLB=8-18)

Detergent (HLB=13-15)

Solubilising agent (HLB=10-18)

31
HYDROPHILIC-LIPOPHILIC BALANCE
(HLB)
HLB values of number of polyhydric
alcohol fatty acid esters such as, glyceryl
monostearate can be estimated by using
the following formula:
HLB = 20(1-S/A)

Where S is the saponification number of

the ester and A is the acid number of the
fatty acid.

32
 HLB According to Griffin

HLB = 20 ( 1 SV / AV )

Where S V = Sap value of ester

AV = Acid value of fatty acid used

Calculation of HLB value of Polyoxyethylene sorbiton

monolaurate (tween 20), for which S= 45.5 and A =
276,

So the HLB = 20[1-45.5/276] = 16.7

The oil phase of an oil in water (o/w) emulsion
requires a specific HLB, called the required
hydrophile-lipophile balance, RHLB
33
HYDROPHILIC-LIPOPHILIC BALANCE
(HLB)
The HLB value of a nonionic surfactant
whose only hydrophilic portion is
polyoxyethylene is calculated by using the
formula
HLB = E/5

Where E is percentage by weight of

ethylene oxide.

34
HLB ACCORDING TO GRIFFIN
(ONLY FOR PEG TYPES)

35
HYDROPHILIC-LIPOPHILIC BALANCE
(HLB)
Davis has given another method for calculating the
HLB values of surface active agents. In this method,
the component groups of the surfactant molecules are
assigned group numbers.
These are added up to give the HLB value for the
surfactant molecule.
HLB = (hydrophilic group numbers) -
(lipophilic group numbers) + 7
Mixtures of surface active agents generally give more
stable emulsions then when used alone.
The HLB of a mixture of surface active agents is
usually assumed to be an algebraic mean of the HLB
values of the two components and can be determined
by the following formula:
HLBmixture = HLB1 * % in the mixture + HLB2 * % in the 36
mixture
REQUIRED HLB (RHLB)
Ithas been found that certain emulsifying
agents of a given HLB value appear to
have the best effect when used in
combination with a particular oil phase.
This has given rise to the concept of
required hydrophilic-lipophilic balance or
RHLB for a given oil or oil combinations,
which is defined as the HLB value that is
required to prepare a stable emulsion of a
particular type. 37
REQUIRED HLB (RHLB)
Thus, for a given oil, the RHLB for
preparing a stable o/w emulsion can be
different from that required to prepare a
stable w/o emulsion.
The RHLB can be determined
experimentally by observing the stability
of emulsions prepared using different
surface active agents or their
combinations.
38
REQUIRED HLB (RHLB)
Table lists the RHLB values for some oil phase
ingredients for both o/w and w/o emulsions.
Oil phase RHLB value RHLB value
for o/w for w/o
emulsion emulsion

Liquid paraffin 10-12 5-6

Paraffin wax 10 4

Bees wax 9-11 5

39
MICELLIZATION
Atlow concentration, surfactant
molecules exist in solution as monomers(
individual molecules of surfactant). At
high concentration the surfactant
molecules saturate the surface and start
forming aggregates in solution called the
micelles(micelles are formed once the
surfactant exceeds a given concentration
called the critical micelle concentration,
CMC).
40
MICELLIZATION
These aggregates which may contain 50 or
more monomers are called micelles and
the process is called micellization.
These micelles have a hydrophobic core
which can solubilize a hydrophobe.

41
MICELLIZATION
The main reason for micelle formation is the
attainment of a minimum free energy state. The
main driving force for the formation of micelles is
the increase of entropy that occurs when the
hydrophobic regions of the surfactant are
removed from water and the ordered structure of
the water molecules around this region of the
molecule is lost.

42
MICELLIZATION

43
MICELLIZATION
CRITICAL MICELLE CONCENTRAION
(CMC)
The concentration of monomers at which
the micelles form is known as
micellization.
The main reason for micelle formation is
the attainment of a minimum free energy
state.

44
MICELLIZATION
Aggregation Number
The number of monomers that aggregate to form
micelles is known as aggregation number.

45
MICELLIZATION
Explanation
the phenomenon of micelle formation can be
explained as follows.
when surfactant are added to water, they first orient
themselves at the liquid-air interface. As more of the
surfactant is added, the molecules adsorbed at the
surface gets crowded until they are so tightly packed
that any further occupancy at the interface would
require compression of the surfactant molecules at
the interface. Further increment beyond this
concentration causes the molecules to aggregate into
micelles. The process begins at a certain
characteristic concentration of the surfactant called
the critical micellar concentration (CMC). 46
MICELLIZATION
After this point any further addition of the
surfactant hardly causes any increase in the
molecules at the interface but the concentration
of micelles or associated molecules increases in
direct proportion to the increase in the overall
surfactant concentration. In dilute solutions, the
micelles are approximately spherical and of the
same size and any increase in the surfactant
concentration only increases the number of
micelles.

47
MICELLIZATION

48
MICELLIZATION
Orientation Of Amphiphiles.
Orientation of amphiphile depends upon the
solvent which may be polar i.e., aqueous or non-
polar.
Orientation In Aqueous Medium.
In case of amhiphiles in water, the hydrocarbon
chains (non_polar) face inward into the micelle to
form their own hydrocarbon environment.
Surrounding this hydrocarbon core are the polar
portions of the amphiphiles associated with the
water molecules of the continuous phase.
49
MICELLIZATION
Orientation In Non_polar Medium.
The orientation of the molecules is now reversed,
with the polar heads facing inwards while the
hydrocarbon chains are associated with the
continuous non_polar phase. (reverse or inverted
micelles) Non_polar solvent
water

oil water

50
Reverse micelles
TYPES OF MICELLES

WATER

WATER

WATER
WATER

Spherical Laminar

51
TYPES OF MICELLES
1.Spherical micelles
Spherical types of micelles exist at and just above
the critical micelle concentration.

2. Cylindrical micelles/lamellar micelles

At high concentrations, lamellar micelles have an
increasing tendency to form and exist in
equilibrium with the spherical micelles.

Ref: cooper and Gunns tutorial pharmacy

52
TYPES OF MICELLES
Note:
Gegenions :a certain number of the sodium ions
are attracted to the surface of the micelle,
reducing the overall charge .these bound ions are
called gegenions.

Na+

Na+

Na+ 53
MICELLIZATION
PROPERTIES OF MICELLES
Micelles are formed at the CMC. Most micelles are
spherical and contain between 60 and 100 surfactant
molecules.
There is an equilibrium between micelles and free
surfactant molecules in solution.
Micelles are dynamic structures and are continually
formed and broken down in solution they should not
be thought of as solid spheres.
The typical micelle diameter is about 23 nm and so
they are not visible under the light microscope.
When the surfactant concentration is increased above
the CMC, the number of micelles increases but the
free surfactant concentration stays constant at the
CMC value. 54
STRUCTURE OF THE MICELLES

55
STRUCTURE OF THE MICELLES

The structure of the micelles formed by

ionic surfactants consists of:
The hydrophobic part of the amphiphile is located in
the core of the micelle.
Stern layer: Around this core is a concentric shell of
hydrophilic head groups with (1 ) N counter ions,
where is the degree of ionization and N is the
aggregation number (number of molecules in the
micelle). This compact region is termed the stern
layer. For most ionic micelles the degree of ionization
is between 0.2 and 0.3; that is, 7080% of the
counter ions may be considered to be bound to the
micelles. 56
STRUCTURE OF THE MICELLES

Shear surface: The outer surface of the stern layer

is the shear surface of the micelle.
Kinetic Micelle: the core & the stern layer together
constitute what is termed the kinetic micelle.
Gouy-Chapman electrical double layer:
Sorrounding the Stern layer is a diffuse layer called
the Guoy-Chapman electrical double layer, which
contains the N counter ions required to neutralize
the charge on the kinetic micelle. The thickness of
the double layer is dependent on the ionic strength of
the solution.

57
THE STRUCTURE OF THE MICELLES
FORMED BY IONIC SURFACTANTS

58
THE STRUCTURE OF THE MICELLES
FORMED BY IONIC SURFACTANTS

59
STRUCTURE OF THE MICELLES

Micelles formed by non-ionic surfactants:

are larger than their ionic counterparts and may
sometimes be elongated into an ellipsoid or rod-like
structure.
Nonionic micelles have a hydrophobic core formed
from the hydrocarbon chains of the surfactant
molecules surrounded by a shell of oxyethylene
chains, which is often termed the Palisade layer.
This layer is capable of entrapping a considerable
number of water molecules.
Shear surface: The outer surface of the palisade
layer forms the shear surface.
60
STRUCTURE OF MICELLE FORMED BY
NON-IONIC SURFACTANTS:

61
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

The effect of micellization on some of the physical

properties of solutions containing surface active
agents or amphiphiles is shown.
Surface Properties:
The adsorption of surface active agents at
the liquid air interface initially causes a decrease
in surface tension till a point when CMC is
reached. At cmc the orientation of surfactant
molecules into micelles removes them from the
bulk and surface and the surface tension remains
constant. Any further addition of surfactant
beyond CMC causes them to form micelles and
the conc. Of monomeric ions remains constant. 62
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

Colligative properties:
Association of monomeric surfactant
molecules into micelles at the CMC causes
a marked change in the colligative
properties of solutions of association
colloids. This is due to a sudden decrease
in the number of colligative units at or
above CMC. Thus, osmotic pressure,
boiling point and freezing point of the
solution show change at or above CMC.
63
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

Electrical conductance:
Generally the molar conductivity of
solutions containing ionic surface active
agents generally decreases at the CMC b/c
of the greater retarding effect of the
oppositely charged atmosphere of
gegenions surrounding the micelles as
compared to that experienced by simple
ions and also due to reduction in the net
charge on micelles due to adherence of 64
some oppositely charged gegenions.
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

However, at high field strengths the

micelles move quite rapidly and oppositely
charged Gegenions cannot exert their
effect. The molar conductivity then
increases instead of decreasing. This is b/c
the inherent conducting power of micelles
is greater than the conducting power of
ions alone.

65
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

Solubility:
Micellesare more soluble than the
monomers. At low temp. solubility of
surface active agents increases slowly
with increase in temperature beyond a
particular temp. , when enough material
is present to allow the formation of
micelles(CMC), the solubility increases
rapidly. The point at which this occurs is
known as the kraft point and the
concentration in solution at this point is
66
the CMC at the kraft temperature.
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

Light scattering:
The scattering of light by solns. Of surface
active agents is increased by the
aggregation of molecules into micelles.
This is b/c particles of colloidal dimension
are being formed which cause greater
scattering of light than simple molecules.
At CMC the amount of light scattered
increases abruptly.
67
INFLUENCE OF CMC ON THE PHYSICAL
PROPERTIES OF SURFACTANT SOLUTIONS

Solubilization:

The property of surface active agents to

cause an increase in the solubility of
organic compounds in aqueous system is
called solubilization. The property is
exhibited at or above CMC only which
indicates that micelles are involved in the
phenomenon.

68
INFLUENCE OF CMC ON THE PHYSICAL PROPERTIES OF
SURFACTANT SOLUTIONS

69
FACTORS AFFECTING CMC
1. The Hydrocarbon Chain
a. Chain length :
An increase in chain length causes a logarithmic
decrease in the cmc at constant temperature.
Increase in length of the hydrocarbon chain results
in a decrease in CMC, which for compounds with
identical polar head groups is expressed by the
linear equation:
log [CMC] = A Bm
where m is the number of carbon atoms in the
chain and A and B are constants for a homologous
series corresponding increase in micellar size.

70
FACTORS AFFECTING CMC

b. Branched hydrocarbon chain.

Branching of a hydrocarbon chain causes an
increase in cmc since the decrease in free energy
arising from the aggregation of branched chain
molecules is less than that obtained with linear
molecules with the same number of carbon atoms.
linear molecule

branched chain
molecule

71
FACTORS AFFECTING CMC
c. Unsaturation.
The CMC is increased by about 3_4 times by the
presence of one double bond when compared with the
value for the analogous saturated compound.
2. The Hydrophilic Group
a. Number of hydrophilic groups
the electrical repulsive force between the adjacent
ions in a micelle increases as the number of ionic
groups increases. In addition an increase in the
number of type of hydrophilic group increases the
solubility of the surface active agent (means
monomers are ore soluble in the solution and have
less tendency to aggregate).Both these effects will 72
lead to an increase in the CMC.
FACTORS AFFECTING CMC
b. Position of hydrophilic group
the cmc tends to increase as the polar
group is moved from the terminal position
towards the mid of the hydrocarbon chain.
c. Nature of the hydrophilic group
In non-Ionics, electrical repulsion b/w
similarly charged ions is absent. Hence
aggregation is facilitated and CMCs are
much lower than those for ionic surface
active agents. 73
FACTORS AFFECTING CMC
3.Type of counter ion
Micellar size increases for a particular cationic
surfactant as the counter ion is changed
according to the series Cl < Br < I, and for a
particular anionic surfactant according to Na+ <
K+ < Cs+.
Ionic surfactants with organic counter ions (e.g.
maleates) have lower CMCs and higher
aggregation numbers than those with inorganic
counter ions.

74
FACTORS AFFECTING CMC
4. Addition of electrolytes
Electrolyte addition to solutions of ionic
surfactants decreases the CMC and
increases the micellar size. This is
because the electrolyte reduces the forces
of repulsion between the charged head
groups at the micelle surface, so allowing
the micelle to grow.
At high electrolyte concentration the
micelles of ionic surfactants may become
non-spherical. 75
FACTORS AFFECTING CMC
5. Effect of temperature
With non ionic surfactants, an increase in
temperature causes a decrease in the CMC as the
micellar size is increased,
Aqueous solutions of many non-ionic
surfactants become turbid at a characteristic
temperature called the cloud point.
At temperatures up to the cloud point there is an
increase in micellar size and a corresponding
decrease in CMC.
76
FACTORS AFFECTING CMC
(Non-ionic surfactants have cloud points
above 100o C. The process is reversible;
that is cooling the solution restores
clarity. The turbidity at the cloud point is
due to separation of the solution into two
phases.)
Temperature has a comparatively small
effect on the micellar properties of ionic
surfactants.
77
APPLICATIONS OF SURFACE ACTIVE
AGENTS

MEDICINAL APPLICATIONS
1. As antimicrobials:

Quaternary ammonium compounds such as

cetyl trimethyl ammonium bromide,
benzalkonium chloride, etc. have useful
antibacterial properties.
These are used as disinfectants for instruments
and skin and as antibacterial agents in creams
and throat lozenges, etc.

78
 The activity of surface active agents arises from
their adsorption at the bacterial cell surface. This
changes the permeability of the cell membrane
and results in loss of essential substances from
the cell resulting in its death.

79
APPLICATIONS OF SURFACE ACTIVE
AGENTS

2. As expectorants: in acute & chronic

infections of the upper respiratory tract,
e.g.., bronchitis, asthma etc the viscosity
of bronchial mucus increases. Inhalation
of sprays containing surfactants loosens
the mucus and provides its easy removal
& relief.
3. As cleansing agents: since surfactants
have detergent properties, these are also
employed as cleansing agents 80
HOW SURFACTANTS WORK

81
APPLICATIONS OF SURFACE ACTIVE
AGENTS

o PHARMACEUTICAL APPLICATIONS
1. As solubilising agents: surface active
agents have been extensively used as
solubilising agents for a number of
poorly soluble drugs such as oil soluble
vitamins such as vitamin A are
unpleasant to take in the form of fish
liver oil but are easily palatable when
administered in the form of oil in water
emulsions or as solubilized system in
82
water.
APPLICATIONS OF SURFACE ACTIVE
AGENTS

Surfactants have also been used to

solubilize many disinfectant compounds
such as cresol and chloroxylenol. Lysol
which is a solution of phenol and an
alkali soap in water is a very good
disinfectant.

83
APPLICATIONS OF SURFACE ACTIVE
AGENTS

As wetting agents: hydrophobic powders

tend to aggregate and agglomerate when
added to water. Dispersions containing
such hydrophobic powders are often
difficult to prepare since the powders
forms large floccules or float on the
surface. Such properties hinder the
preparation of a uniform suspension.

84
APPLICATIONS OF SURFACE ACTIVE
AGENTS

The problem is usually overcome by the

use of surfactants which get adsorbed at
the solid/liquid interface and increase the
affinity of the hydrophobic powder for
water while reducing the attractive forces
b/w particles of the solid. Aerosol OT is a
very good example of wetting agent.

85
APPLICATIONS OF SURFACE ACTIVE
AGENTS

3. As flocculating agents:
Use of surfactants coupled with precipitation
brings about controlled flocculation in
suspensions which is often desirable. For
example sulfamerazine being a hydrophobic
powder can be dispersed by means of aerosol OT
but the particles tend to settle on standing and
may eventually forms a cake. If aerosol OT is
added in association with aluminum ions,
controlled flocculation of the particles take
place. Although these flocculated particles settle
on standing, they do not form a hard cake and
get easily dispersed in the vehicle on shaking. 86
APPLICATIONS OF SURFACE ACTIVE
AGENTS

4. As emulsifying agents:
Many synthetic and naturally occurring
surfactants are widely used as
emulsifying agents. These act by
reducing the interfacial tension b/w the
oil phase and water phase by forming a
stable interfacial film b/w the two.
Examples of such agents include tweens,
spans, cetomacrogols and natural
compounds such as acacia and 87
tragacanth.
APPLICATIONS OF SURFACE ACTIVE
AGENTS

5. As additive in semisolid
preparations:
Surfactants are often added to
ointments and creams in order to alter
the release characteristics of the
incorporated drug.
The capacity of different ointment
bases to take up aqueous liquids can also
be improved by the addition of
surfactants. 88
IF QUESTION IS ASKED ABOUT THE PROPERTIES OF
SURFACTANTS THEN YOU CAN WRITE THE DETAIL
OF FOLLOWING APPLICATIONS
- Wetting
- Emulsification
- Solubilization
-Flocculation

89
 SOLUBILIZATION
Solubilization
Solubilisation is the process whereby
water-insoluble or partly soluble
substances are brought into solution by
incorporation into micelles.
Solubilizate
Solubilized substance or the substance
whose solubility is increased by micellar
involvement in a solution is called
solubilization.
90
SOLUBILIZATION

91
SOLUBILIZATION
Maximum additive concentration (MAC).
The maximum amount of solubilisate that can be
incorporated into a given system at a fixed
concentration is termed the maximum additive
concentration (MAC).
Determination of Maximum additive
concentration (MAC).
The simplest method of determining the MAC is to
prepare a series of vials containing surfactant
solution of known concentration. Increasing
concentrations of solubilisate are added and the vials
are then sealed and agitated until equilibrium
conditions are achieved. The maximum concentration
of solubilisate forming a clear solution can be
determined by visual inspection or from extinction or
turbidity measurement on the solutions. 92
DETERMINATION OF MAXIMUM
ADDITIVE CONCENTRATION (MAC).

93
 SOLUBILIZATION

The site of solubilization within the micelle is

closely related to the chemical nature of the
solubilizate
Non-polar solubilizates (aliphatic hydrocarbons) or
completely water insoluble hydrophobic molecules
are dissolved in the hydrocarbon core of ionic and
non-ionic micelles.

94
SOLUBILIZATION
Hydrophilic solubilizates or polar solubilzates
can be adsorbed on the surface of the micelle.

95
SOLUBILIZATION
Amphipathic solubilizates
or

Solubilizates with intermediate

hydrophobicities or
Water-insoluble compounds
containing polar groups
are orientated in the palisade layer
with the polar group at the core
surface interface of the micelle, and
the hydrophobic group buried inside
the hydrocarbon core of the
96
micelle.(mixed micellization)
SOLUBILIZATION
In addition to these sites, solubilization in non-
ionic polyoxyethylated surfactants can also occur
in the polyoxyethylene shell (palisade layer)
which surrounds the core.

97
SOLUBILIZATION

98
SOLUBILIZATION
Co-micellization
Micellar solubilization can occur only in the
presence of micelles.
Often amphipaths form micelles in the
absence of solubilizate and occasionally due
to addition of solubilizate micelle formation
occurs.
Thus, Addition of an amphiphilic solubilizate
to amphipath may reduce the CMC
sufficiently for mixed micelles to form and
the process is called Co-micellization 99
SOLUBILIZATION
Hydrotropy.
Sometimes a fourth substance other than
amphipath, water and solubilizate is added to
increase the solubility of solubilizate. This effect
of non-micelle forming amphipaths is known as
hydrotropy.

100
 FACTORS AFFECTING SOLUBILIZATION

1. Nature of the surfactant

Structural characteristics of a surfactant
affect its solubilising capacity b/c of its effect
on the solubilising site within the micelle.
In cases where the solubilisate is located
within the core or deep within the micelle
structure, the solubilisation capacity
increases with increase in alkyl chain length.
For example there is an increase in
solubilising capacity of a series of
polysorbates for selected barbiturates as the
alkyl chain length is increased from C12 to
C18.
101
FACTORS AFFECTING SOLUBILIZATION
an increase in ethylene oxide chain length of a
polyoxyethylated nonionic surfactant leads to an
increase in the total amount solubilised per mole
of surfactant b/c of the increasing number of
micelles.

102
FACTORS AFFECTING SOLUBILIZATION
2. Nature of solubilizate:
An imp. Property of surfactant micelles is their
ability to solubilize water insoluble compounds.
The location of solubilisate in the micelles is
closely related to the chemical nature of the
solubilisate.
In general, non_polar solubilzates are localized in
the micellar core.
Water insoluble compounds are oriented with the
hydrophobic group in the core and polar groups
towards the surface.
103
FACTORS AFFECTING SOLUBILIZATION
For a homologous series, an increase in the size
of a hydrocarbon group decreases the solubility in
a solution of an amphipath of given
concentration.
Branching of alkyl chain has only a small effect
but unsaturation increases the solubility.

104
FACTORS AFFECTING SOLUBILISATION
3. Effect of electrolytes:
Salts have been shown to increase the
solubility of hydrocarbons in amphipath
solutions.
Salts promote the formation of micelles by
lowering of CMC.
Salts also cause an increase in micelle size
therefore increasing the solubilizing
capacity.
105
FACTORS AFFECTING SOLUBILISATION
4. Effect of temperature:
In general amount of drug solubilized
increase with an increase in
temperature.
The effect is particularly pronounced
with some non ionic surfactants where
its a consequence of an increase in the
micellar size with temperature.

106
FACTORS AFFECTING SOLUBILISATION
5. Effect of pH:
The main effect of pH on the solubilizing
power of non ionic surfactants is to alter
the equilibrium b/w ionised and
unionised drug.
The unionised form is more hydrophobic
form & is solubilized to a greater extent
in the micelles than an ionised form.

107
PHARMACEUTICAL APPLICATIONS OF
SOLUBILISATION

Pharmaceutical applications of
solubilisation
1. Formulation of insoluble drugs
A wide range of insoluble drugs have been
formulated using the phenomenon of
solublization.
a. Phenolic compounds
The phenolic compounds such as cresol,
chlorocresol, chloroxylenol and thymol are
frequently solubilized with soap to form clear
solutions for use in disinfection.
108
PHARMACEUTICAL APPLICATIONS OF
SOLUBILIZATION
b. Iodophors (Solubilised solutions of iodine in
non-ionic surfactant micelles)
Non-ionic surfactants are efficient solubilizers of
iodine, and will incorporate up to 30% iodine by
weight, of which three quarters is released as
available iodine on dilution. Such iodine-
surfactant system (referred to as IODOPHORS)
are more stable than iodine-iodide systems. They
are preferred in instrument sterilization since
corrosion problems are reduced.
There is also evidence of an ability of Iodophors
solution to penetrate hair follicles of the skin, so
enhancing activity. 109
PHARMACEUTICAL APPLICATIONS OF
SOLUBILISATION

c. Steroids
The low solubility of steroids in water presents a
problem in their formuation for ophthalmic use.
The requirements of optical clarity preclude the
use of oilly solutions or suspesions and there are
many examples of the use of non_ionic
surfactants as a means of producing clear
solutions that are stable to steriliztaion. In most
formulations, solubilization has been achieved
using ploysorbates or polyethylene sorbitan
esters of fatty acids.
110
PHARMACEUTICAL APPLICATIONS OF
SOLUBILISATION

d. Essential oils.
Essential oils are extensively solubilised by
surfactants, polysorbates 60 and 80 being
particularly well suited to this purpose.
e. Water insoluble vitamins.
Non-ionic surfactants are also employed in the
preparation of aqueous injections of the water
insoluble vitamins A, D, E and K. polysorbate 20
and 80 being the best two solubilizers.
f. Other drugs.
Many other drugs have been formulated in this
way, including the analgesics, sedatives, 111
sulfonamides and antibiotics.
PHARMACEUTICAL APPLICATIONS OF
SOLUBILIZATION
2. Improvement of taste.
drugs of unpleasant taste can be solubilised to
mask the taste e.g. multivitamin preparation.
For this purpose amphipaths must be non-toxic
having agreeable taste and odor.
3. Enhanced absorption
Solubilization leads to enhanced absorption. It
improves the intestinal absorption of vitamin A.
it also improves drug absorption from ointment
bases.
4. Drug stability
Vitamin A is more resistant to auto-oxidation in 112
aqueous non-ionic surfactants than in oils.
REFERENCES:
Physicochemical principals of pharmacy By
Alexander T Florence and David Attwood
Physical pharmacy by S.P. Agarwal & Rajesh
Khanna
Pharmaceutical Dosage Forms and Drug
Delivery, Second Edition By Ram I. Mahato, Ajit
S. Narang (factors affecting Solubilization)
Tutorial pharmacy by Cooper & Gunns

113