Micellization

With the increasing concentration of amphiphiles i.e. after CMC certain physical properties show profound deviation from their general trends Some of these properties show increasing trend while other show decreasing trend This is due to the self-association of monomers to form micelles The process of forming micelles is known as micellization. Micelles are always of dynamic equilibrium that means, number of monomers associate to form micelle remain same however some monomers leave micelle while other monomers from the bulk join micelles to keep the number constant. Micelles: As the concentration of monomer is increased, aggregation occurs over a narrow concentration range. These aggregates which may contain 50 or more monomers are called micelles. A micelles lie within the size range of colloidal system. CMC: the concentration of monomer at which micelles form is termed as the critical micelle concentration. Micellization: the process of micelle formation is known as micellization Compounds forming micelles are called: Surfactant, surface active agent or amphiphiles There are drugs which also from micelles and are known as micellar drugs e.g. cholorquine, diphenhydramine, orphenadrine, chlorphenoramine etc.

Types of Micelles

Micelle Shape as Per Type of Surfactant

General Surfactant Type Simple surfactants with single chains and relatively large head groups Simple surfactants with relatively small head groups, or ionic surfactants in the presence of large amounts of electrolyte Double-chain surfactants with large head groups and flexible chains Double-chain surfactants with small head groups or rigid, immobile chains Double-chain surfactants with small head groups, very large, bulky hydrophobic groups Expected Aggregate Structure Spherical or ellipsoidal micelles

Relatively large cylindrical or rod-shaped micelles Vesicles and flexible bilayer structures Planar extended bilayer structures Reversed or inverted micelles

Increasing and Decreasing Trend of Micelles

These properties can be used to determine the CMC.

Determination of CMC
Below the CMC the concentration of amphiphiles undergoing adsorption at the air-water interface increases as the total concentration of amphiphiles is raised. Eventually a point is reached at which both

the interface and the bulk phase become saturate with monomers. This is called CMC. Any further amphiphiles added in excess of this concentration aggregates to form micelles in the bulk phase and in this manner the free energy of the system is reduced. It affects some physical properties of the system. Some properties shows increasing trend while some other shows decreasing trend.

E.g. the surface tension decreases up to the CMC and above the CMC, the surface tension remains constant, this shows that the interface is saturated and micelle formation has taken place in the bulk phase.

Factors affecting the CMC and Micelle Size

Nature of the Hydrophobic Group
Hydrophobic group plays important role in determining type of association of group. Micellar amphiphiles have hydrocarbon groups constracted from hydrocarbon chains. Increase in length of this chain will decrease CMC and increase aggregation number. Many drugs are surface active agents and form micelles. For example, diphenyl methane drugs. (diphenhydramine, orpheradrine, chlorphennoxamine etc.) Hydrophilicity/ Hydrophobicity and substitute on such drugs play very important role in the determination of CMC and Aggregation number Some representative examples:

 Antiparkinoism Drugs are used to reduce muscular rigidity neurological disorder marked by hypokinesia (abnormally diminished motor activity tremor and muscular rigidity).

Other Examples Phenothiazine Tranqulizer Priomazine Chlorpromazine Promethazine

Antidepressants Imipramine Amitriptyline Nor-triptyline They have tricyclic hydrophilic moieties Many aromatic and hetero aromatic ring structure (dyes, purines, pyrimidine) associate in non- micellar process.

Nature of Hydrophilic Group

Ionic hydrophilic groups of amphiphiles show different properties then Non- ionic hydrophilic groups may be due to difference in charge. In general non-ionic surfactants have low CMC and high aggregation numbers although they have same length of hydrocarbon chain. This is because in non-ionic surfactant no electrical work during the process of micellization.

Effect of the Counter-ion

In case of cationic surfactant as the counter ion is charged in series, Cl-, Br-, I- , micelle size is an increase in order for Cl-< Br-< I- . In case of anionic surfactant as the counter ion is charged in series ,Na+, K+, Cs+, micelle size is an increase in order for Na+< K+ <Cs+ . More weakly hydrated a counter ion larger the micelle formed.

Effect of hydrophobic group

If hydrophobic group is aromatic, micelle does not form. Length of hydrocarbon chain is directly proportional to micelle size & inversely proportional to CMC. We express this in mathematical term, Log [CMC] = A Bm Where, A & B are homologous series constant. m is the no. of carbon atom in chain.

Addition of Electrolytes
Electrolytes reduce the charges (force) on ionic surfactants so there is reduction in the magnitude of the force of repulsion between the charges had groups on the micelles. Hence, there is reduction in CMC and increase in aggregation number.

Effect of Temperature
This effect in particularly seen in non-ionic surfactants. Solution of non-ionic surfactants when heated they turn turbid at a characteristic temperature known as cloud temperature Turbidity at cloud point is due to separation of the solution into two phases. i.e. dispersed phase of dispersion medium. At temperature up to cloud point there is increase in Aggregation No. and decrease in CMC. Temperature has no profound effect on CMC and aggregation No. of Ionic Surfactant.

Application
Micelle increases bioavailability of poorly soluble drugs. Polymeric micelle is used to target the tumor site by passive as well as active mechanism. Micelle is used in ophthalmic drug delivery system that effectively delivers the drug to posterior tissue of eyeball. Micelle is used to encapsulate the antibiotic & anticancer drugs.