Surface Active Agents

(SAA)
Objectives
By the end of this lecture, the student
will be able to:
1. Illustrate the structure of SAA
2. Classify SAA and enumerate their
uses and predict factors affecting
Critical Micelle Concentration (CMC)
3. Define adsorption and predict factors
affecting it 2
 Surface Active Agents (SAA)

• A surfactant molecule is a cylinder representing

the hydrocarbon (hydrophobic) portion with a
sphere representing the polar (hydrophilic) group
attached at one end.
• The hydrocarbon chains are straight

Sodium Lauryl Sulfate

molecule
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• Molecules and ions that are adsorbed at
interfaces are termed surface active agents,
surfactants or amphiphile
• The molecule or ion has a certain affinity for both
polar and nonpolar solvents.

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• Depending on the number and nature of the polar
and nonpolar groups present, the amphiphile may
be hydrophilic, lipophilic or be reasonably
well-balanced between these two extremes.
• It is the amphiphilic nature of surface active
agents which causes them to be adsorbed at
interfaces, whether these be liquid/gas or
liquid/liquid.
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• A scale showing classification of surfactant
function on the basis of HLB values of
surfactants.
• The higher the HLB of a surfactant the more
hydrophilic it is.
• Example: Spans with low HLB are lipophilic.
Tweens with high HLB are hydrophilic.
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 Determination of HLB

 Polyhydric Alcohol Fatty Acid Esters (Ex.

Glyceryl monostearate)
HLB = 20 ( 1 – S / A )
S = Saponification number of the ester
A = Acid number of the fatty acid

 Surfactants with hydrophilic portion have only

oxyethylene groups
HLB =E / 5 8
 Surfactants with no Saponification no (Ex. Bees
wax and lanolin)

HLB =E + P / 5

E = The percent by weight of ethylene oxide

P=The percent by weight of polyhydric alcohol
group in the molecules
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 Functional Classification

According to their pharmaceutical use, surfactants

can be divided into the following groups:
 Wetting agents
 Solubilizing agents
 Emulsifying agents
 Dispersing, Suspending and Defloculating agents
 Foaming and antifoaming agents
 Detergents 10
 Wetting agents
 Wetting agent is a surfactant that when
dissolved in water, lower the contact angle and
aids in displacing the air phase at the surface
and replacing it with a liquid phase.
 Solids will not be wetted if their critical surface
tension is less than the surface tension of the
liquid. Thus water with a value of 72 dynes/cm
will not wet polyethylene with a critical surface
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tension of 3 1 dynes/cm.
 A good wetting agent should reduce the surface
tension of a liquid to a value below the solid
critical surface tension.
S = γ S – (γ L + γ LS )
 When the forces of adhesion are greater than the
forces of cohesion, the liquid tends to wet the
surface and vice versa.

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• According to the wettability, the drop will make a
certain angle of contact with the solid.
• A contact angle is lower than 90°, the solid is
called wettable
• A contact angle is wider than 90°, the solid is
named non-wettable.
• A contact angle equal to zero indicates
complete wettability.

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 complete no
incomplete wetting
wetting wetting

Ө = 0°   Ө    90° <Ө   90° =Ө   90° > Ө 180° =

γ s – γsL> 0 γ s – γsL ≈ 0 γ s– γsL< 0

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 The surface of liquid water (meniscus) has
a concave shape because water wets the
surface and creeps up the side
 The surface of Mercury has a convex
shape it does not wet glass because the
cohesive forces within the drops are
stronger than the adhesive forces between
the drops and glass.
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 SAA at Interfaces

• As a Surface active substance contains a

hydrophilic and a hydrophobic portions, it is
adsorbed as a monolayer at the interfaces.

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17
At water-air interface
• Surface active molecules will be adsorbed at
water-air interfaces and oriented so that the
hydrocarbon chains of are pushed out of the
water and rest on the surface, while the polar
groups are inside the water.
At oil-water interface
• The hydrophobic portion is inside the oil phase
and the hydrophilic portion inside the water
phase.
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At low surfactant concentrations:

At higher concentrations:

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 Micelle Formation

• At certain concentration the interface and the bulk

phase become saturated with monomers
• Excess surfactants add will begin to agglomerate
in the bulk of the solution forming aggregates
called Micelle
• The lowest concentration at which micelles first
appear is called the critical concentration for
micelle formation [CMC ]
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• For different surfactants in dilute aqueous
solutions, this number ranges approximately from
25 to 100 molecules.
• The diameters of micelles are approximately
between 30 and 80 Ao( 3-8 nm).
• Micelles are not permanent aggregates. They form
and disperse continually.

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 Micelle shape
 Normal spherical micelles
 Inverted spherical micelles
 Cylindrical and lamellar micelles

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 Factors affecting CMC
For nonionic surfactants
Temperature CMC
For ionic surfactants
 The CMC are higher for ionic than nonionic
surfactants
Effect of electrolytes on the CMC of ionic
surfactants
The addition of salts to ionic surfactant
solutions reduces the electric repulsion between
the charged groups and lower CMC values
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Electrolyte has small
or no effect on the
CMC of non-ionic
surfactants. 25
 Effect of Surfactant’s
structure on CMC
• In polar solvents:
• Polarity of Surfactant molecules CMC
• Length of hydrocarbon chain CMC
• In non-polar solvents:
• Polarity of Surfactant molecules CMC
• Length of hydrocarbon chain CMC

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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+.
• Ionic surfactants with organic counter ions (e.g.
maleates) have lower CMCs and higher
aggregation numbers than those with inorganic
counter ions.
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28
 Micellar Solubilization
• Micelles form around the molecules of the water
insoluble compound inside the micelles’ cores
and bring them into solution in an aqueous
medium. This phenomenon is called micellar
solubilization.
• The inverted micelles formed by oil soluble
surfactant can solubilize water-soluble compound
which is located in the center of the micelle, out
of contact with the solvent. 29
• Micelles of nonionic surfactants consist of an
outer shell containing their polyethylene glycol
moieties mixed with water and an inner core
formed by their hydrocarbon moieties.
• Micellar solubilization does not take place
below the CMC.
• So dissolution begins at the CMC.
• Above the CMC, the amount solubilized is
directly proportional to the surfactant
concentration.
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• Compounds that are extensively solubilized
increase the size of micelles in two ways:
 The micelles swell because their core volume
is augmented by the volume of the solubilizate.
 The number of surfactant molecules per
micelle increases.

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 Detergents

 Detergents are surfactants used for removal of dirt.

 Detergency involves:
• Initial wetting of the dirt and the surface to be cleaned.
• Emulsification or solubilisation of the dirt particles
• Finally washing away the dirt.

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 Structural Classification
 Surfactant may be classified into:
 Ionic surfactants
 Anionic surfactants: the surface active part is anion
(negative) e.g. sodium lauryl sulfate
 Cationic surfactants: the surface active part is cation
(positive) e.g. Quaternary ammonium salts
 Ampholytic surfactants: contain both positive and
negative ions e.g. dodecyl-B-alanine.
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 Non-ionic surfactants
 Widely used in pharmaceutical formulations e.g. Tweens
and Spans.
 They are polyethylene oxide products.
 Surfactants based on sorbitan are of pharmaceutical
importance.

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 Esterification of the primary hydroxyl group with
lauric, palmitic, stearic or oleic acid forms
sorbitan monolaurate, monopalmitate,
monostearate or monooleate
 These are water-insoluble surfactants called Span
20, 40, 60 or 80, respectively.
 Addition of about 20 ethylene oxide molecules
produces the water-soluble surfactants called
polysorbate or Tween 20, 40. 60 or 80. 35
 Sorbitan

Sorbitan monostearate (Span 60)

Polyoxyethylene sorbitan
monostearate (tween 60)

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 Adsorption at solid liquid interface

 It is a surface phenomenon
 Adsorption is the adhesion of atoms, ions, of gas,
liquid, or solids to a surface
 This process creates a film of the adsorbate (the
molecules or atoms being accumulated) on the
surface of the adsorbent.
 Adsorbate: the material being adsorbed.
 Adsorbent: the solid material being used as the
adsorbing phase (e.g., activated carbon). 37
 It is different from absorption, in which a
substance diffuses into a liquid or solid
 The term sorption contains both processes, while
desorption is the reverse of adsorption.

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 There are two general types of adsorption:
1. Physical adsorption, in which the adsorbate is
bound to the surface through the weak van der
Waals forces.
2. Chemical adsorption or chemisorption, which
involves the stronger forces.
 Adsorption data may be analysed using the
Langmuir and Freundlich equations

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The Langmuir equation is:
c/(x/m) = 1/ab + c/a
Where:
x is the amount of solute adsorbed by a weight, m, of
adsorbent, c is the concentration of solution at
equilibrium, b is a constant related to the enthalpy of
adsorption and a is related to the surface area of the solid.

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The Langmuir is based on four assumptions:
1. The surface of the adsorbent is uniform, that is,
all the adsorption sites are equivalent.
2. Adsorbed molecules do not interact.
3. All adsorption occurs through the same
mechanism.
4. At the maximum adsorption, only a monolayer is
formed
 Many deviations from the Langmuir equation can
occur especially at high concentration
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The Freundlich equation is:
log (x/m) = log a + (1/n) log c
Where
1/n is a dimensionless parameter and is related to the
intensity of drug adsorption.
Systems that obey this equation, adsorption results in the
formation of multilayers rather than a single monolayer.

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 Common Adsorbents
 Activated carbon also called activated charcoal: it
is extremely porous and thus have a very large
surface area available for adsorption
 Silica gel - hard, granular, porous material
 Activated alumina - aluminum oxide

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 Factors affecting adsorption
1. Solubility of the adsorbate.
 In general, the extent of adsorption of a solute is
inversely proportional to its solubility in the
solvent from which adsorption occurs.
 Adsorption from solution increases as the
molecules become more hydrophobic

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2. pH
 In general, for simple molecules adsorption
increases as the ionization of the drug is
suppressed, the extent of adsorption reaching a
maximum when the drug is completely unionized
 With amphoteric substances: at isoelectric
point→↓ ionization and solubility→↑ adsorption
 Adsorption of non electrolytes is not
greatly affected by the pH value of the
solution
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3. Nature of the adsorbent
 The extent of adsorption is proportional to the
specific surface area (the more finely divided or
the more porous the solid → ↑ adsorption.
 Size of the molecule with respect to size of the
pores (large molecules may be too large to enter
small pores and this may reduce adsorption)
4. Temperature
 Since adsorption is generally an exothermic
process, an increase in temperature normally
leads to a decrease in the amount adsorbed.
5. Contact time or residence time
 The longer the time the more complete the
adsorption will be
6. Affinity of the solute for the adsorbent
 The surface of activated carbon is only slightly
polar. Hence non-polar substances will be more
easily picked up by the carbon than polar ones.
 ↑ number of carbon atoms → lower polarity → ↑
adsorption (e.g., the degree of adsorption
increases in the sequence formic-acetic
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 Pharmaceutical applications of adsorption
1. Adsorption of poisons/toxins (gas masks)
2. Taste masking
3. Haemoperfusion
4. Adsorption in drug formulation
5. Purification of water

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Adsorption may cause problems in formulation:
 Drugs or other materials such as preservatives are
adsorbed by containers, thereby reducing the effective
concentration.
 Certain additives, such as the parabens, may be adsorbed
on to the solid material present in a suspension, leading to
a loss in antimicrobial activity.
 The adsorption of insulin on to intravenous administration
sets has been reported,
 The sorption of phenylmercuric acetate, used as a
preservative in eye drops, on to polyethylene containers