Micellization and their pharmaceutical applications. Micelles are aggregates of surfactant molecules that form spontaneously above a critical concentration. They consist of a hydrophobic core surrounded by a hydrophilic shell. Micelles can increase the solubility of poorly soluble drugs and protect drugs from degradation, thus improving their stability and bioavailability. They also show potential for targeted drug delivery applications such as cancer therapy. Factors like critical micelle concentration, temperature, and electrolyte concentration affect micelle formation and properties.

1. MICELLIZATION AND
THEIR
PHARMACEUTICAL
APPLICATIONS
By
Maria Shuaib

2. Contents
 Introduction to micelles
 Process of micellization
 Factors affecting micellization
 Critical micelle concentration (CMC)
 Factors affecting CMC
 Determination of CMC
 Thermodynamic aspects
 Pharmaceutical applications

3. Micelle
 A micelle is an electrically charged particle
formed by an aggregate of molecules, above a
critical concentration and occurring in certain
colloidal electrolyte solutions, especially those of
soaps and detergents.

4. Micelle
A micelle is an aggregate of surfactant molecules
dispersed in a liquid colloid.
The process of forming micelle is known as
micellization.

5. Introduction
5
 In dilute solution Amphiphiles tend to reduce Surface
tension
 As concentration molecules of amphiphiles goes on
increasing they disturb hydrogen structure, to
minimize the disturbance molecules tend to form
aggregate into a structure
 Structure called as micelle and Amphiphilic molecule
Surface Active Agent

6. PHYSICOCHEMICAL
BACKGROUND
6
 cohesive forces between molecules down into liquid
 the intermolecular attractive forces is called surface
tension

7. Micelle formation
7
•Typical micelle is Spherical in structure which
contain 50-100 monomers
•Number of monomers to form micelle is called as
aggregation number

8. • A micelle is an aggregate of monomer surfactant
molecules dispersed in a liquid colloid.
• Hydrophilic "head" regions in contact with
surrounding solvent, sequestering the hydrophobic tail
regions in the micelle centre. (oil-in-water micelle).
• Inverse micelles have the head groups at the centre
with the tails extending out (water-in-oil micelle).
Micelle
8

9. 9
SAA bulk Concentration
Surface excess
Surface saturated with SAA
Excess in the bulk
Micelles( colloidal aggregates)

10. Oil in water type
Because of arrangement
monomers micelle is capable
to hold lipidic nature drug at
centre

11. Water in oil type
In Reversed micelle at middle
able to hold relatively large
amounts of water in their
interior. In that way, a "pocket"
is formed which is particularly
suited for the dissolution and
transportation of polar solutes
through a non polar solvent.

12. Factors affecting process of
micelles formation
 Molecular wt. of monomer
 Aggregation no.
 Proportion of hydrophobic and hydrophilic chain
length
 Preparation process
 CMC

13. Critical micelle concentration
(CMC)
13
 The lowest concentration at which micelles
first appear is called the critical concentration
for micelle formation
 The critical micelle concentration is the point at
which surfactant molecules aggregate together
in the liquid to form groups known as micelles.

14. 14
 The critical micelle concentration of a surfactant
indicates the point at which surface active properties
are at an optimum and performance is maximised.
 The CMC is the concentration above surfactant when
micelles will form spontaneously.
 Increase in concentration of surfactant beyond CMC
change number size or shape but not provide
increase in concentration of monomeric species

15. Determination of the CMC
15
 Micelles are formed at the critical micelle
concentration (CMC), which is detected as an
inflection point in physical properties which are
plotted as a function of concentration.
• surface tension,
• Conductivity,
• Turbidity,
• Osmotic Pressure

16. 16
1. At very low
concentrations of
surfactant only slight
change in surface
tension is detected.
2. Additional
surfactant
decreases surface
tension
3.Surface becomes
fully loaded, no further
change in surface
tension.

17. 17

18. Factors Affecting CMC
18
 Structure of hydrophobic group. –
length of hydrocarbon chain is
Micelle size CMC
 Addition of Electrolyte
Micelle Size CMC
 Effect of Temperature
up to cloud point
Micelle Size CMC

19. Thermodynamic aspect
 The formation of micelle can be understood using
thermodynamics: micelles can form
spontaneously because of balance between
entropy and enthalpy
 For ionic surfactants, the solubility of a material
will often be observed to undergo a sharp,
discontinuous increase at some characteristic
temperature, commonly referred to as the Krafft

20.  A surfactant, when present at low concentrations in a system,
adsorbs onto surfaces or interfaces significantly changing the
surface or interfacial free energy
 Primary reason of micelle formation is attainment of minimal free
energy
 Free energy change ∆G depend upon both Etropy,S and Enthlpy
H at temperature T
∆G= ∆H-T∆S (T∆S is 90-95% value of ∆G)

21. Pharmaceutical Applications
 Micelles are an important factor of
pharmaceutical chemistry and have a number of
applications which give them great importance
in delivering medicines to patients, or to specific
locations within the patient

22. Solubilization
 Micelle can be used to increase the solubility of
material that are normally insoluble or poorly
soluble in dispersed medium phenomenon
called as solubilization

23. Solubilization
 Solubilization can be defined as ‘‘the
preparation of a thermodynamically stable
isotropic solution of a substance normally
insoluble or very slightly soluble in a given
solvent by the introduction of an additional
amphiphilic component or components.

24. Solubilization by micelles
 The location of a solubilized molecule in a
micelle is determined primarily by the chemical
structure of the solubilizate.
 Solubilization can occur at a number of different
sites in a micelle

25. 1. On the surface, at the micelle–solvent interface,
2. At the surface and between the hydrophilic head groups,
3. In the palisades layer, i.e., between the hydrophilic groups and the first few
carbon atoms of the hydrophobic groups that comprises the outer regions of
the micelle core.
4. More deeply in the palisades layer, and in the micelle inner core.

26.  Hydrophilic drugs can be adsorbed on the surface of
micelle
Drugs with intermediate Solubility should be located in
intermediate positions within the micelle such as
between the hydrophilic head group of Peo Micelles
Completely insoluble hydrophobic drugs may be
located in the Inner Core of the micelle.

27. Examples
 1. Polar alcohols are soluble in aqueous
solution, so it located in solution / on surface of
micelle.
 2. Phenol are having polar –OH group and non
polar benzene ring. In which –OH gr. Located in
hydrophilic environment and benzene ring in
hydrophobic environment, so it located at the
surface and between the hydrophilic head

28.  3. Semi polar materials, such as fatty acids are
usually located in the palisades layer, the depth
of penetration depending on the ratio of polar to
non-polar structures in the solubilisate molecule.
 4. Non-polar additives such as hydrocarbons
tend to be intimately associated with the
hydrocarbon core of the micelle.

29. Example of improved solubility of drugs using
polymeric micellar system
DRUG AMPHIPHILIC POLYMER COMENT
Camptothesin Pluronic p-105,d-tocopherol
Peg 1000 succinate
Increased micellar stability
& bioavailability
Increased cytotoxicity
Docetaxel Polyethylene oxide-b-polystyrene oxide Increased solubility
Griseofulvin
Pacletaxel
EmBn (E-oxyethylene,B-oxybutylene)
N-octyl-o-sulfate chitosan
Solubilization independent of
B block length, when it
exceeds about 15B units
Improved bioavailability &
reduce cytotoxicity

30. Drug Protection
 Protection of drug molecules from degradation
via hydrolysis or other physicochemical
reactions — this increases their shelf life, or
prolongs their stability during use.

31. Targeted Drug Delivery
 Micelles may have an increasingly important
role as carriers of drug molecules to target sites,
for example, delivering doxorubicin to a tumour.

32.  Polymeric micelles, self-assembling nano-
constructs of amphiphilic copolymers, are widely
considered as convenient nano-carriers for a
variety of applications, such as diagnostic
imaging, and drug and gene delivery.

33. Conclusion
33
 By using Phenomenon of micellization we improve
solubility of API
 Considering factor of CMC we modify micelle size
Shape & release profile

34. Conclusion
 Applying this knowledge in field of Pharmacy
Improve API stability
Maintain Bioavailability long period
 Research is continued in Targeted DDS
(Cancer)

35. References
35
 A. N. Martin, Martin's Physical Pharmacy and
Pharmaceutical Sciences, 6th edition, p.
 M.E. Aulton, Pharmaceutics science of dosage
form design, 2nd Edition, p. 88-89
 Leon Lachman, The Theory and Practice of
Industrial Pharmacy, 3rd edition, p. 106
 H.A. Liebereman, M.M. Rieger, G.S. Banker,
Pharmaceutical Dosage Forms: Disperse
Systems,2nd Edition, Vol.3, p. 216-220

36. 36
 Sanjay K. Jain, Vandana Soni, Benley’s Text
Book of Pharmaceutics, p.68-74
 Ram I. Mahato Pharmaceutical Dosage Forms
and Drug Delivery,CRC press pharmacy
education series, p.111-119
 Nita K. Pandit & Robert R. Soltis, Introduction to
the Pharmacetical Sciences 2nd Edition, p.54-55
 Online Reference
http://www.biolinscientific.com/attension/applicatio
ns/?card=AA8

37. References
 Martins physical pharmacy & pharmacuetical
sciences maryland USA lippincott williams &
wilkins:2007 pg no. 469-97
 Moroi y.micelles: theorotical &applied aspects
springer international ed. New york:springer:2005
pg no.41-50
 Jones mc ,leroux jc polymeric micelles: a new
generation of colloidal drug carriers. Eur j pharm
biopharm 1999 pg no.101-11

38. References
 Torchilin VP. Micellar nanocarriers:
pharmaceutical perspectives. Pharmaceutical
Research 2007:24:1–16.
 Chen H, Khemtong C, Yang X et al.
Nanonization strategies for poorly water-soluble
drugs. Drug Discovery Today 2011:16:354–60.