Micellization is the process where surfactant molecules spontaneously self-assemble into aggregates called micelles above a critical concentration known as the critical micellar concentration (CMC). Micelles form to minimize contact between the surfactant hydrophobic tails and water. The CMC and micelle size are affected by factors like the surfactant chain length and head group, counter ion type, temperature, and presence of additives. Micelles can incorporate hydrophobic drugs to improve their solubility and stability for drug delivery applications.

1. Presented by:- Christy P George
M. Parma 1st year
Department of Pharmaceutics
BHARATI VIDYAPEETH UNIVERSITY POONA COLLEGE OF
PHARMACY,PUNE

2. TOPICS DISCUSSED:-
 MICELLISATION
 STRUCTURE OF MICELLES
 SHAPE OF MICELLES
 SIZE OF MICELLES
 FACTORS AFFECTING CMC AND MICELLAR SIZE

3. SURFACTANTS
They are low to moderate molecular weight compounds
with a hydrophobic part and a hydrophilic part
[amphiphile].
Based on the nature of polar head groups they are
classified as
Anionic surfactants
Cationic surfactants
Non ionic surfactants
Zwitter ionic surfactants

5. SURFACTANTS IN AQUEOUS SYSTEM
Surfactants when dissolved in aqueous system
Hydrophobic part - more water insoluble
Hydrophilic part – more water soluble
But the contact between water and hydrophobic part is
energetically less favorable resulting in
Hydrophobic
domain Align by
the surface or
interface
Hydrophobic
domain aggregate
to form various
structures

6. AGGREGATION STRUCTURE
 Micelles
 Micro
emulsions
 Range of
liquid
crystalline
phases

7. MICELLES
 Micelles are basically aggregation structure formed by the surfactants.
Each single surfactants are called as monomers. When the concentration
is increased aggregation occurs over a narrow concentration range
 Aggregation number – it is the number of monomers that aggregate to
form a micelle
 Micelles are aggregates with 50 or more monomers. (50 Armstrong
diameter)
CriticalMicellar
Concentration(CMC)
When the concentration of surfactants
are increased in the solution
micellization occurs at a narrow
concentration range. The
concentration at which the micelle
is formed is called critical micellar
concentration

8. MICELLIZATION
• Amphiphiles
gets adsorbed at
interface
Below cmc
• Interface and
bulk face gets
concentrated
with monomers
cmc • Any further
addition of
amphiphiles they
gets aggregated to
form micelles
Above cmc
Micellization is a process of aggregation of surfactant ions or molecules above critical
concentration to form self-assembly structures referred to as micelles.

9. • Interaction of hydrophobic
partsDriving forces
• Electrostatic repulsive
interaction
• Repulsive osmotic
interaction
• Steric interaction of bulky
head groups
Opposing forces
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

10. ELECTRICAL PROPERTIES OF INTERFACE
POTENTIAL DETERMINING
IONS
COUNTER IONS
NERNST POTENTIAL(potential
at the solid surface)
ZETA POTENTIAL(potential at
the shear plane of stern layer )
ELECTRICAL DOUBLE LAYER
Particles dispersed in liquid media gets charged in
two ways
•Adsorption of ionic species from solution
•Ionization (depends on ph and degree of
ionization)

11. MICELLE STRUCTURE [ionic, zwitter ionic ]
•Liquid core-
formed by the n
number
hydrocarbon chains
•Stern layer- ionic
head groups + (1-
alpha) n counter
ions
•Diffusion layer or
gouy Chapman
layer- alpha n
counter ions
Location of
interface is
0.08nm above the
alpha carbon of
alkyl chains

12. Outermost boundary of the
stern layer corresponds the
hydrodynamic shear surface of
the micelles. The core and the
stern layer form the kinetic
micelle.
Total charge is given as
α*n*e (where n is the number
of monomers, e is elementary
charge and alpha is degree of
ionization)
Surface potential of kinetic
micelle is electrophoretic zeta
potential

13. MICELLE STRUCTURE[non ionic]
Typical example of
non ionic micelles is
those formed by
polyoxyethylated
surfactants. Its main
components are
 Core
 Palisade layer
Core is surrounded
by a layer of
polyoxyethylene
chains to which
solvent molecules
may be hydrogen
bonded. This region
of micelle is called
palisade layer.

14. MICELLAR SHAPE
 Micelles are dynamic
structures with a liquid
core. So it is unrealistic to
regard them as rigid
structures with precise
shape
 Micellar sphericity –
micelles are assumed
spherical structure for all
experimental
considerations
 Small micelles – they are
assumed to have
ellipsoid structure.
Maximum number of
monomers can be
included in this shape

15. FACTORS AFFECTING MICELLAR SHAPE
 Concentration
 Flexible rod like aggregates are observed at high concentration.
 E.g.:- in CTAB(cetyltrimethylammoniumbromide) a transition from
spherical to rod shape is observed
 Temperature
 Presence of electrolytes
 At high electrolyte concentration the micelles of ionic surfactants may
become non-spherical.
Micelle shape undergo transition to more
asymmetric form when there is change to these
parameters

16. POLYDISPERSITY OF MICELLES (size of micelles)
 Polydispersity is the
measure of the
heterogeneity of sizes
of molecules or
particles
 It is expressed as a ratio
of weight average(nw)
to number average(nn)
 Size distribution curves
are plotted from data
obtained by methods
like ultrasonic
absorption technique
Size distribution curve of polymeric surfactants

17. FACTORS AFFECTING CMC AND MICELLAR SIZE
Nature of the
hydrophobic
group
Nature of
hydrophilic
group
Nature of
counter ion
Effect of
additives
Effect of
pressure
Effect of
temperature

18. NATURE OF HYDROPHOBIC GROUP
CHAIN
LENGTH OF HYDROCARBON
Hydrophobic groups are mostly
composed of hydrocarbon chains
CMC
 CMC decreases linearly as the
number of carbon atom increases.
 For ionic surfactants cmc is halved
as the length of the hydrocarbon
chain is increased by one
methylene group
 For chains of greater length than 16
carbon atom this relationship
declines due to coiling.

19.  For non ionic surfactants cmc is
decreased one third as one
methylene group is added. It has
more pronounced decrease in cmc
compared to ionic surfactants
 For branched chains the effect is less
prominent compared to straight
chain
 The relationship can be expressed as
log cmc =A-Bm,
where A and B are constants for
homologous series and m is the
number of carbon atoms in the
chain
SIZE
 Increased chain length increases
hydrophobicity and thereby
increase micellar size. Linear
relationship exist between
log(micellar weight) and carbon
chain length

20. INTRODUCTION CF3 GROUP
 Substitution of the CF3(more hydrophobic) group for terminal CH3 group of
the surfactants hydrocarbon chain doubled the cmc. Since CF3 is hydrophobic
it was expected to promote micellization but it was observed to increase the
cmc (or impede micellization)
 This is observed due to the mutual phobicity of hydrocarbon and fluorocarbon
moieties
EFFECTS OF OTHER GROUPS
 Surfactants possessing two hydrocarbon chains attached to a single head form
lamellar structures
 Addition of phenyl group increases cmc.
 Presence of substituent's (-Cl, -Br, -I, F, -CH3) increase cmc
 Aromatic hydrocarbon tends to form association structures( non micellar)

21. NATURE OF HYDROPHILIC GROUP
There is difference between cmc
of ionic and non ionic surfactants
with identical hydrophobic
groups. This depends on nature
the hydrophilic groups. Main
aspects are
 Ionic surfactants are reported to
have a higher cmc compared to
non ionic surfactants. This is due
to the increased electrical work
required to form the micelles.
 An increase in the ethylene
oxide chain length of a non-
ionic surfactant makes the
molecule more hydrophilic and
the CMC increases.

22.  Mean distance between the counter ion and the charge centre of
the surfactants affect the size of micelles.
E.g. decylammonium bromide forms very much larger micelles than
decyltrimethylammonium bromide because the Br- counter ions are
able to approach the charged nitrogen atom more easily thus effectively
shielding the electrical forces and allowing larger micelles to form
 Solvent interaction like formation of hydrogen bonds may affect the
size of micelles
 Position of ionic groups also affects the cmc
e.g.:- increase of cmc when sulphate group is moved from terminal to
medial position in sodium alkyl sulphates

23. EFFECT OF ADDITIVES
 Electrolytes
 Electrolyte addition to solutions of ionic surfactants decreases the CMC
and increases the micellar size. Eg. Aggregation number of sodium
dodecyl sulphate (NaDS) micelles show large variation
 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. Equation relating cmc and electrolyte concentration is given as
log CMC = -alogcc + b (a and b are constants related to ionic groups
cc total counter ion concentration)
• Lowering of cmc of
polyoxyethylated non ionic
surfactants is observed but it is
comparatively small

24.  Inorganic Electrolytes
 Inorganic additives have appreciable effect on cloud point of non ionic
surfactants. Two categories of additives are identified that make change
to cloud point.
(a)urea and salts with anion known to break the water structure such
as iodides, thiocynates etc
(b)salts with cations
 Alcohols
 Addition of lower alcohols to ionic surfactant causes a decrease in the
cmc which becomes more pronounced with increase in hydrophobicity
of added alcohol
 Linear relationship between cmc and the number of carbon atom in
the alcohol molecule was established in a series of potassium soaps
 In non ionic surfactants lower alcohols causes increase in the
cmc(weakening of hydrophobic bond) and higher alcohols causes
increase. (penetration of alcohol in the palisade layer)

25. NATURE OF COUNTER ION
 In ionic surfactants the change of the counter ion to one of greater
polarizability or valence leads to decrease in cmc and corresponding
increase in aggregation number
 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.

26. EFFECT OF TEMPERATURE
 Temperature has a comparatively small effect on the micellar
properties
 Decrease in the cmc of ionic surfactants with temperature is observed
initially. This is due to the dehydration of monomers. Condition
reverses at raised temperatures

27.  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.
 Increase in temperature results in a decreased micellar size

28. EFFECT OF PRESSURE
 An increase in cmc with pressure increase has been observed up to
pressure of 150 M pa followed by decrease
 This can be due to solidification of the micellar interior or change in
the dielectric constant of water at high pressure
 Dissociation of monomers is observed at low pressure while association
at high pressure

29. MICELLE SYSTEM IN DRUG DELIVERY
 Through enhanced soluabilisation more amount of
sparingly soluble drug can be incorporated in an
aqueous solution.
 Decreased hydrolytic degradation and enhanced
stability.
Drugs containing esters and anhydrides are
hydrolytically sensitive and becomes unstable in
presence of moisture. E.g. indomethacin stabilized by
polymeric micelles
E.g. are various non polar drugs which are solubilised by
micelles. nimeusilide can be solubilized by micellisation

30.  Controlling release rate of drug.
 Effective masking of taste of noxious drug can be
achieved by micellization.
 It also helps in the intra venous delivery of drug
IV administration of drug results in rapid clearance and
accumulation of drug in tissues associated with reticuloendothelial
system. micelles can be effectively used here to restrict the action of
RES
E.g. in cancer therapy prolonged blood stream circulation and
reduced RES uptake can be attained by using micelles

31. Reference
 Martin Malmsten. Surfactants And Polymers In Drug
Delivery. Drugs And Pharmaceutical Science series
volume 122
 Alfred Martin, James Swarbrick, Arthur Cammarta.
Physical Pharmacy. 3rd edition
 Research papers