SURFACTANTS

surface-active molecules

molecules which accumulate at surfaces

Dr Sudaxshina Murdan
Department of Pharmaceutics 1
D Micellisation

2
Hydrophilic headgroup goes into the water

Hydrophobic tail escapes into the air as it hates water

A few surfactant molecules are dissolved in

the water
3
Keep adding more and more surfactant into the beaker
Keep adding more and more surfactant into
the beaker

What happens when the liquid/air interface

is saturated with surfactant molecules ?

5
 Micellisation takes place, i.e. Micelles are formed

A micelle is formed when surfactant molecules aggregate/self-assemble

in the bulk phase of a medium.

This is driven by the need to shield the hydrophobic part of the molecule
from the (aqueous) medium. Water molecules are excluded from the
micellar core.

Micelles in dynamic equilibrium with monomers in solution.

i.e. they are continuously breaking and forming

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 Micelle

Imagine a micelle as a ball in 3-dimension

The surfactant headgroups form the skin of the ball

The surfactant tails form the core of the ball

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 Micellisation - micelle formation.

Micellisation is driven by the need to shield the hydrophobic part of the

molecule from the medium.

Micelles may also be formed in other polar solvents e.g. formamide,

propylene glycol.

8
 Inverted micelles
In a non-polar medium, where the hydrophobic tails can
interact with the medium, and the headgroups do not,
inverted micelles are formed.

9
Critical Micelle Concentration (CMC) – Concentration of surfactant
molecules in a medium, at which micelles start to form

10
Aggregation number - number of surfactant molecules in a micelle

e.g. SDS micelles, aggregation number is 60-70, at 25oC.

11
Micelle size –

The radius of micelle core is close to the extended length of the alkyl chain.

12
 Micellar structure

Ionic vs non-ionic micelles

++ + + + ++
+ +++
+
+
+ ++
+ +
+ + +
+
+ +

Surfactant headgroups are positively

charged. Let’s not forget the
counterion, here Cl-
 Micellar structure

Ionic vs non-ionic micelles

Cl-

++ + + + ++
Cl- Cl-
+ +++
+
+
Cl- +
++
+ + Cl-
+ + +
+ +
+ Cl-
Cl-

Ionic micelles have low aggregation number, and adopt a spherical or near-
spherical shape

Non-ionic micelles: these are larger compared to ionic micelles.

Why? In charged micelles, work is done to add a monomer to an existing charged
micelle. This work is not needed in non-ionic micelle.
 Non-ionic surfactants. Draw the micelles of these
surfactants. Note: the Tween 80 has a hydrophobic tail, a
headgroup and then a region with oxyethylene groups
which are hydrophilic

H O O H Span 60
O

o o
O H

Tween 80

15
 Homework

draw the micelles of Tween 80

and of Span 60

16
 Micellar structure

Certain non-ionic micelles have a shell of oxyethylene chains which is

often termed the palisade layer.

Palisade layer of micelle is capable of entrapping water molecules.

Thus the micelles are highly hydrated.

Draw more of these on

micelle above
17
 The micelled formed by the surfactant with
the longer hydrocarbon chain will be larger

A. True
B. False

18
 The micelled formed by the surfactant with
the longer hydrocarbon chain will be larger

A. True
B. False

19
 The surfactant with the longer hydrocarbon
chain will have a lower CMC

A. True
B. False

20
 The surfactant with the longer hydrocarbon
chain will have a lower CMC

A. True
B. False

21
 The ionic surfactant will have a
lower CMC

+
Cl-

A. True
B. False
22
 The ionic surfactant will have a
lower CMC

+
Cl-

A. True
B. False
23
 The ionic surfactant will have a
higher aggregation number

A. True
B. False
24
 The ionic surfactant will have a
higher aggregation number

A. True
B. False
25
 The surfactant with the larger head group
will have a lower CMC

A. True
B. False
26
 The surfactant with the larger head group
will have a lower CMC

A. True
B. False
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The CMC of Tween 80 in water is 0.0014 g/100ml;
CMC of Tween 20 in water is 0.0060 g/100 ml

Which is more water-soluble?

A. Tween 80
B. Tween 20

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The CMC of Tween 80 in water is 0.0014 g/100ml;
CMC of Tween 20 in water is 0.0060 g/100 ml

Which is more water-soluble?

A. Tween 80
B. Tween 20

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Factors affecting Critical Micelle Concentration and
micellar size

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 Factors affecting CMC and micellar size

• structure of hydrophobic group

surfactants - hydrophobic groups commonly hydrocarbon chains

Increased hydrocarbon length leads to increased micellar size

Increased hydrocarbon length leads to decreased CMC

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 Factors affecting CMC and micellar size

• structure of hydrophobic group

compounds with rigid aromatic or heteroaromatic ring structures –

stepwise, face-to-face stacking of molecules, one on top of another.

No CMCs Aggregates increase continuously in size

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Factors affecting CMC and micellar size (cont.)
• nature of hydrophilic group

there are pronounced differences between ionic and uncharged

surfactants

1. In general, non-ionic surfactants have

lower CMC values and
higher aggregation numbers

why? Mainly because no electrical work is involved.

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Factors affecting CMC and micellar size (cont.)
• nature of hydrophilic group

2. Increased hydrophilic group leads to increased hydrophilicity, this leads

to higher CMC

(High hydrophilicity of surfactant = high solubility = low tendency to form

micelles)

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 Factors affecting CMC and micellar size (cont.)

Cl- Cl-
• Nature of counterion ++ + + + ++
Cl-
Cl- Cl-
+ ++Cl-
+
+
Cl- + Cl-
Cl- + +++Cl-
+ + Cl-
CH3 ++ +
CH +N R Cl- +
+ Cl-
2
Cl- Cl-
CH3
Cl- Cl-

Cationic surfactant: counterion e.g. Cl-, Br-, I-

Anionic surfactant: Counterion Na + , K + , Cs+

Let’s look at the size of the counterion first.

35
36
 Factors affecting CMC and micellar size (cont.)

Counterion size Cl- < Br- < I-

Counterion size Na+ < K+ < Cs+

Cl-
Cl-
++ + + + + + Cl-
Cl-
Cl-
+ +++Cl-
+
Cl- +
Cl- +
++ Cl-
+ + Cl-
++ + Cl-
Cl-
++
+ Cl-
Cl-
Cl- Cl- 37
 Factors affecting CMC and micellar size (cont.)

• Nature of counterion

Increasing size of counterion results in:

1. increasing micellar size.

2. reduced CMC.

Why?

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Increasing size of counterion results in increasing micellar size and
reduced CMC.

Increased (↑) size of counterion means ↑ ionic radius means ↓ ionic

field

Br-
Cl-

large counterions are less solvated (surrounded by solvent, here water, molecules)

Therefore large counterions can be more readily adsorbed on the micellar surface

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 Cl-
Cl-
++ + + + ++
Cl-
Cl- Cl-
+ +++Cl-
+
Cl- +
Cl- +
++ Cl-
+ + Cl-
++ + Cl-
Cl-
++
+ Cl-
Cl-
Cl- Cl-

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 Cl- +
Br- + Br-
+ +
+ +
+ + +
+
++ Br-
+ + + +
++ Br- + + Br-
Cl- + Cl- +
Br- + Br-
+
+ + ++ + +
+
++
+ +++
+ ++ + +
+
Cl- + + Cl- Br- + + Br-
+
+ +
+
+ + Br-
+
+ + +
+ +
Cl-
+ ++ + Br-
Cl- + Br- + + + + +
+ +
Br-
+

IN above, more Br- counterions can adsorb onto the micellar surface, therefore

the charge repulsion between ionic surfactant head groups is reduced to a

greater extent than when Cl- is the counterion.

So, it’s easier for more surfactant molecules to be added to a micelle which
grows, i.e. Br- (a larger counterion) allows a larger micelle to be formed.
Aggregation number of the micelle is therefore larger.

CMC is also lower as it is easier to form micelles

 Factors affecting CMC and micellar size (cont.)
• Addition of electrolytes

+
Br- + Br-
+ +
+ +
+ +
+
++ Br- + +
Br- +
+ Br-
Br- + Br-
+
+ +
+
++
+++
+ +
+ Br-
+
+
Br- +
+
+ + Br-
+
+ +
++ + Br-
Br- + + +
+
+ +
+
Br-
+

42
 Factors affecting CMC and micellar size (cont.)
• Addition of electrolytes (say let’s add NaCl to a micellar solution)

Cl-
Cl-
+
+ +
Br- + Br- +
+ Br-
+ +
+
+ + + +
Cl Br-
- +
+ Br-
+
Br- + Br-
+ +
+ +
+ +
+
++ Br- + + Br-
+
+ Br- +
Br- + Br- + + Cl-
+ +
++
Br- + Br-
+ Cl- + +
+ + + +
+ Br-
+ +
+
+++ ++ Br- +
+ +
+ Br-
+
+ + Br-
+
+
+ + +
Br- + Cl- ++ + Br-
+ + Br-
+
+
+ + Br- + + +
+
+ +
++ + Br- +
+Br- Cl- Cl-
Br- + + +
+
+ +
+
Br-
+

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 Factors affecting CMC and micellar size (cont.)
• Addition of electrolytes (say let’s add NaCl to a micellar solution)

Cl-
Cl-
+
+ +
Br- + Br- +
+ Br-
+ +
+
+ + + +
Cl Br-
- +
+ Br-
+
Br- + Br-
+ +
+ +
+ +
+
++ Br- + + Br-
+
+ Br- +
Br- + Br- + + Cl-
+ +
++
Br- + Br-
+ Cl- + +
+ + + +
+ Br-
+ +
+
+++ ++ Br- +
+ +
+ Br-
+
+ + Br-
+
+
+ + +
Br- + Cl- ++ + Br-
+ + Br-
+
+
+ + Br- + + +
+
+ +
++ + Br- +
+Br- Cl- Cl-
Br- + + +
+
+ +
+
Br-
+
Repulsion among cationic surfactant headgroups is
reduced by Cl-,
So, it is easier to form micelles and for more surfactant
molecules to join a growing micelle, which grows.
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i.e CMC decreases and micelle size increases
 Factors affecting CMC and micellar size (cont.)
• Addition of electrolytes

Addition of electrolytes lowers the CMC and increases micellar size

Addition of electrolytes means there are more counterions, which can reduce the
repulsion between charged head groups in micelle

Thus less electrical work is needed in the formation of micelles.

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46
 Solubilisation

(enhancing drug solubility using surfactants)

You can imagine a micelle as a liquid hydrocarbon droplet covered with

polar headgroups. The micellar core is a paraffin-like region which can
dissolve oil-soluble molecules. Thus, one can use surfactants to
increase the solubility of poorly water-soluble drugs.

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 Solubilisation

(enhancing drug solubility using surfactants)

For example, 55mg phenobarbital is solubilised

per gram of the non-ionic surfactant, Tween 20.

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Increasing drug solubility using surfactants

Solvent molecule

Solute molecule

Surfactant molecule

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micelle
 Solubilisation
(enhancing drug solubility using surfactants)

• Solubilisation: process whereby water-insoluble substances are

brought into solution by incorporation into micelles.

• Solubilisation does not occur until micelles are formed.

• Above CMC, increase in concentration of surfactants leads to

increasing number of micelles which leads to increasing amount of
solubilisate (that which is solubilised)

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 Location of solubilisate
• Location is related to chemical nature of solubilisate

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 Location of solubilisate

• solubilisate within core results in increase in micelle

size, as the micelle core is enlarged.
Aggregation number of the micelle also increases as
more surfactant molecules join a micelle.

• solubilisate in palisade leads to

no change in aggregation number, but increase in micelle
size due to solubilisate molecules.

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 Pharmaceutical applications of solubilisation:
some examples

• Phenolic compounds, such as, cresol, chlorocresol, solubilised with soap to form clear
solutions which are widely used for disinfection

• Non-ionic surfactants solubilise iodine (iodophors), used for instrument sterilisation.

• Iodophor is also able to penetrate hair follicles of skin which enhances activity of iodine.

• Steroids are poorly soluble in water. Non-ionic surfactants e.g. polysorbates have been
used to produce clear solutions for ophthalmic use

• Polysorbates have been employed to prepare aqueous injections of water-insoluble

vitamins A, D, E, K

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 References
• Aulton’s Pharmaceutics, The design and manufacture of
medicines, Aulton and Taylor, 5th edition

• Physicochemical Principles of Pharmacy

In Manufacture, Formulation and Clinical Use, Florence and
Attwood, 6th edition

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