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Pharmaceutics 356C

Chapter 14
Disperse Systems
(Suspensions, Emulsions, Surfactants, and Aerosols)

Disperse or Polyphase Systems
• Definition: A dispersion is a system containing one
or more constituents distributed throughout a
homogeneous medium
• Can classify dispersions into three categories based
on particle size
– True Solutions—less than 0.001 micron
– Colloids—0.001 to 0.5 microns
– Coarse Dispersions—greater than 0.5 microns
(Much overlapping in such a classification)

Disperse or Polyphase Systems
• True Solutions
– Molecular dispersions
– Particles are invisible even with the electron microscope
and pass through filter paper and semi- permeable
• Colloidal Dispersions (Sols)
– An intermediate state between true solutions and
– Particles cannot be seen with an ordinary microscope but
can be seen with the electron microscope
– In addition, while the particles of a colloidal dispersion will
still pass through filter paper they will not pass through
semi-permeable membranes
– Very high surface area
– Particles diffuse more slowly than those of a true solution
Disperse or Polyphase Systems
• Coarse Dispersions
– The systems we know as emulsions or
– Particles (dispersed phase) are often visible with
the naked eye (unaided)
– Will not pass through filter paper or semi-
permeable membranes
– Particles seldom diffuse
– Are used extensively in pharmaceutical products

Types of Colloidal Systems

• There can be many types of colloidal dispersions

• Each phase may be a solid, liquid or gas
• The most important colloidal pharmaceutical
preparations include:
– 1. Foams
– 2. Aerosols
– 3. Emulsions
– 4. Suspensions
– 5. Ointments
– 6. Gels
– 7. Magmas and Mucilages
Basis of Classification

• In general colloids may be divided into three

main groups
• This division is made on the basis of how the
colloidal particles react with the dispersion

Basis of Classification
– Lyophilic (or Hydrophilic Colloid)
• Solvent loving—attraction to dispersion medium (water or
alcohol) – hydrophilic / alcophilic
– Natural Polymers (and charge):
» Acacia (-), Tragacanth (-), Xanthan Gum (-), Protamines
– Cellulose Derivatives (and charge):
» Methylcellulose (none), Sodium Carboxymethylcellulose (-)
– Synthetic Polymers (and charge):
» PVP (none), Carbomer (-)
– Particulate Colloids (and charge):
» Bentonite (colloidal hydrated aluminum silicate) (-),
Veegum (colloidal aluminum magnesium silicate) (-)

Basis of Classification
– Lyophobic (or Hydrophobic Colloid)
• Low attraction to dispersion medium—must put a
lot of energy into system
• Requires special method to manufacture
– Particle size reduction or particle condensation by
– Association Colloids
• Amphiphilic colloids (polar and nonpolar parts of
• Decrease surface tension (surfactants)

Preparation of Colloids
• Hydrophilic colloidal dispersions
– Spontaneously disperse, no special methods
• Hydrophobic colloidal dispersions
– Ultrasonic generators
• >20,000 Hz
– Colloid mills
• Less efficient; broad particle size distribution

Colloid Mill

Properties of Colloids
• Kinetic Properties
– Brownian movement
• Random movement of particles in dispersion
• Observed by SEM
• Due to bombardment of small particles by
molecules of dispersion medium

Properties of Colloids
• Optical properties
– Tyndall effect – light scattering
– True solution – no visible cone
– Colloid – visible cone due to light scattering
– Hydrophilic colloids have less pronounced
Tyndall effect than hydrophobic colloids

Light through mist from ultrasonic nebulizer
Light through colloidal dispersion of silver.
Properties of Colloids
• Diffusion
– Movement of particles from areas of high
concentration to areas of low concentration to
establish equilibrium – Fick’s First Law
– dQ = -DA (dc/dx) dt
– Amount (dQ) of substance diffusing in time (dt) across
plane of area (A) is directly proportional to change in
concentration (dc) with distance traveled (dx)
– D influenced by diffusant properties, solvent
properties, temperature – is not constant but depends
on conditions

Properties of Colloids
• Sedimentation
– Stoke’s Law v = 2r2 g (ρ – ρo) / 9η
– Where:
v is rate of sedimentation
r is radius of particle
η is viscosity of dispersion medium
g gravitation constant
ρ is particle density
ρ o is density of dispersion medium

Properties of Colloids
• Viscosity
– Measure of resistance of a liquid to flow, the more
viscous the liquid the greater force required to make it
flow at a particular rate
– Liquid composed of parallel “layers” or plates
– F/A = η dv/dx
• F/A is shear stress (F applied to area A)
• dv/dx is shear rate (velocity of shear; distance between
• Often plotted: dv/dx = 1/η (F/A)
φ =1/η (fluidity)
– Unit of viscosity – centipoise (cPs)

Shearing force required to produce
velocity gradient between parallel
plates of a block material




Top plane moves at constant velocity (dv) – each lower layer moves at
Velocity proportional to its distance from the fixed bottom layer (dx) –
Result is shear of liquid. 18
Properties of Colloids - Flow
– Newtonian Flow
– Rate of shear linearly related shearing stress
– Influence of temperature
– Examples:
» Castor oil
» Ethyl alcohol
» Glycerin
» Olive oil
» Water
» Milk
» Sugar Solution
» Mineral Oil

F/A = η (dv/dx)
dv/dx = 1/η (F/A) (slope = fluidity or 1 / viscosity)
Properties of Colloids - Flow
– Non-Newtonian Flow
• Plastic Flow
– Apparent viscosity decreases with increasing rates of
– Van der Waals attractive forces must be overcome for
flow to start
– Yield value – material begins to flow when forces
between attractive particles is overcome; is elastic before
then behaves like Newtonian liquid after yield value is
– Yield value indicates force of flocculation between
particles (> degree of flocculation = higher yield value)
– Flocculated particles in suspension are characteristic of
plastic flow
F/A = η (dv/dx)
dv/dx = 1/η (F/A) (slope = fluidity or 1 / viscosity)

Properties of Colloids
– Non-Newtonian Flow
• Pseudoplastic Flow
– Shear thinning materials
– No yield value
– Increasing rates of shear will decrease viscosity
– Examples are polymer dispersions (e.g. Tragacanth,
Sodium Alginate, Methylcellulose, Sodium CMC)
– Polymers in solution, with shear stress, long chain
molecules begin to align themselves in direction of flow
to reduce internal resistance

F/A = η (dv/dx)
dv/dx = 1/η (F/A) (slope = fluidity or 1 / viscosity)

Properties of Colloids
– Non-Newtonian Flow
• Dilatant
– Shear thickening materials
– Increased resistance to flow as the shear rate is
increased with agitation
– Examples include dispersions with >50% solids of small
deflocculated particles, pastes

F/A = η (dv/dx)
dv/dx = 1/η (F/A) (slope = fluidity or 1 / viscosity)

Properties of Colloids
– Thixotropy
• Isothermal and slow recovery, on standing, of a consistency
lost through shearing
• Asymetric particles form loose 3-dimensional structure that
when lost takes time to reform
• Hysteresis loop – measure of thixotropic breakdown, the
larger the hysteresis loop the more thixotropic the liquid is.
• Useful property to formulate liquids to control settling
• Examples include Bentonite Magma

Approximate Viscosities of Gels at
RT (mPa s or cPs)
• Acacia 30% 100
• Alginic acid 0.5% 20
• Guar gum 1% 2,000
• HPMC E4 2% 4,000
• HPMC K100 2% 100,000
• MC A4 2% 4,000
• Starch 2% 13
• Xanthan gum 1% 1,400
Properties of Colloids
• Electrical Properties of Colloids
– Zeta potential – governs degree of repulsion or attraction
between adjacent like charged dispersed particles
– Difference in potential between the surface of a tightly bound
layer and the electroneutral region of the solution
– Hydrophobic colloids have critical zeta potential
• above critical zeta potential – repulsive forces > attractive forces
• below critical zeta potential – attractive forces > repulsive forces
(controlled flocculation)
– Manipulate zeta potential
• Oppositely charged electrolytes to lower zeta potential
• Add another colloid with opposite charge to lower zeta potential
– Zeta potential – gives indication of stability of a colloidal system
– WE WANT: controlled flocculation or reduction of repulsion in
order to stabilize dispersion
Properties of Colloids
• Protective Colloids
– Hydrophobic colloids are difficult to stabilize
due to large surface area and large free
surface energy, particles will flocculate to
reduce energy
– Coat hydrophobic colloid with hydrophillic
colloid to stabilize
– Examples include gelatin, acacia, albumin,
tragacanth, methylcellulose, Na oleate


• Definition -A heterogeneous system in which the
continuous phase is a liquid or semisolid, and the
dispersed phase consists of a dispersed solid
• Acceptable properties of a suspension:
– 1. Particles should not settle rapidly
– 2. When particles settle, should not form hard cake (i.e. be
readily dispersible)
– 3. Product should be viscous enough so patient gets
uniform dose, but not so viscous to prevent pouring or

Pharmaceutical Suspensions

• Heterodisperse systems
• Particles often > 1 um (usually > 10 um)
• Complex continuous phase
– Viscosity Inducing agents, flavors, etc.
• Particle shapes non-spherical
• High solids content

Why Use Suspensions?
•1. No suitable solvent available to dissolve drug (i.e. ZnO)
•2. Mask unpleasant taste of drugs
– (i.e. chloramphenicol palmitate, Chloromycetin, Parke-Davis )
– garlic-like taste for chloramphenicol
– palmitate salt masks taste ,
– also more stable in gastric juices so increased blood levels
– at pH 3-6, palmitate hydrolyzes
•3. To increase chemical stability
– Ex. Penicillin G rapid hydrolysis in solution
– Procaine Penicillin G no hydrolysis if decrease solubility
below 1.5 mcg/ml. (G = glutamate)
•4. To Control Therapeutic Response
– Insulin—Different Release Rate
– Depot Systems—Suspension Injections for time release

Stoke’s Law

•Most important law controlling

formulation of suspensions
•In equation:
– V = rate of settling of the particles
– r = radius of the particles
– p = density of the particles
– po= density of the medium
– g = gravity constant
– η = viscosity of the dispersion
– Stokes Law assumes:
• Particles are spherical
• Suspensions are dilute (<2% w/v)
• Particles do not flocculate
• No Brownian movement
• No electrical effects 38
Stoke’s Law Applications

• Pharmaceutically we can control

suspensions by:
1.) Radius of the particles (r)
V α r2 (Decrease radius, then increase SA and
increase surface energy)
-a high surface energy leads to aggregate formation,
so use a peptizing agent (Na+ citrate in calamine
lotion) to place surface charge on the particles so
they do not aggregate, and the surface charge
repels the particles
- aggregates form to reduce (minimize) surface energy.
Stoke’s Law Applications
• Pharmaceutically we can control suspensions
2.) Viscosity (η) of the medium—Suspending Agents
--Rate of settling is inversely proportional to viscosity
Examples of suspending agents:
-acacia, tragacanth – In, too sticky for Ex
-Carboxymethylcellulose (CMC) –In or Ex
-Veegum (montmorrilonite clays) -use hydrated, In
or Ex
-Carbopol -a gum, use in pH range 5-10, In or Ex
--Viscosity inducing agents -swell in water to increase
Methods of Preparation of

• A. Dispersion Method -add dispersion medium to finely

divided particles
– 1. Diffusible powders—no suspending agent required, will
remain suspended long enough for uniform dose
• Ex: Kaolin, Mg Carbonate, Mg Oxide, Quinine sulfate and
Bismuth subcarbonate—Completely insoluble
2. Indiffusable powders—suspending agent required, does not
remain suspended long enough for patient
• Ex: Aspirin, sulfa drugs, sulfur in topical preps. Salicylic acid,

General Method of Preparation
• 1. Material must be finely divided
• 2. Add small amount of vehicle to make smooth, lump free
• 3. Slowly dilute with remainder of vehicle with constant stirring
(3/4 volume of prep.) in mortar
• 4. Add, through gauze, to pre-calibrated bottle, rinse mortar
with remainder of vehicle into cylinder
• 5. qs to volume with rinse in cylinder

• NOTE: If suspension is thick, use calibrated bottle to qs with

• NOTE: With soluble solids, add as solution AFTER forming
initial dispersion (same with tinctures). If
add before, aggregates will form

Fritsch Planetary Micro Mill

For reducing particle size down

To colloidal size range, dry or in

For mixing and homogenizing of

emulsions, suspensions, pastes.

Uses grinding balls for high impact


Methods of Preparation of
• 1. Chemical interaction (Lotio Alba, White Lotion)
sulfurated potash + zinc sulfate
("stink") + ("zinc")
K2S + ZnSO4 K2SO4 + ZnS

• prepare as separate solutions, filter, add "stink" to the "zinc"

slowly with stirring, obtain fine, white ppt (zinc polysulfides)
• used as astringent (acne)
• 2. Alteration of solvent

Interfacial Properties of
Suspended Particles
• Thermodynamically unstable:
--Flocculate--light, fluffy conglomerates held by weak
Van der Waals forces
--Aggregates--caking –stronger forces to form solid
(Trying to overcome free surface energy in

∆F = γ SL ∆A

Interfacial Properties of Suspended
• To approach a thermodynamically stable
ΔF = O by: reduce interfacial tension–Use
reduce interfacial area—Control
flocculation (Using Zeta Potential)
--Flocculated particles: weakly bonded
settle rapidly
no cake
--Deflocculated particles: settle slowly
difficult to re-suspend

Sedimentation Volumes
Bismuth Subnitrate (+)
• Sedimentation Monobasic Potassium Phosphate (-)
produced by
adding varying
amounts of
• Examples b and
c are

F = Sedimentation Volume
F = Vu = Final Volume of Susp. Sediment
Vo Original Volume of Susp 47
Caking Diagram
Bismuth Subnitrate (+)
Monobasic Potassium Phosphate (-)

• Demonstrating the
flocculation of a
bismuth subnitrate
Apparent Zeta Potential
(+ charged) 1.0
suspension by
means of the 0.5
flocculating agent,
F = Sedimentation Volume
F = Vu = Final Volume of susp. Sediment
Vo Original Volume of susp 48
Examples of Official Suspensions
1. Chloramphenicol Palmitate Oral Suspension
(Chloromycetin Palmitate Suspension, Parke-
-Derivative increases stability and masks taste
-palmitate deriv. is hydrolyzed off in GI tract and
chloramphenicol is absorbed.
-for eye and ear drops, derivative not necessary
because acid stability or taste are not
USE: against gm (-) and gm (+) bacteria
Caution -blood dyscrasias (bone marrow
Examples of Official
1. Calamine Lotion USP
8% ZnO + 8% Calamine
(calamine consists of 98% ZnO + 2% Fe203)
-powders are levigated with glycerin, then paste is diluted
with Bentonite Magma + calcium hydroxide
USE: protectant, relieves itching, sunburn pain, poison ivy
2. Phenolated Calamine Lotion USP
Calamine Lotion USP + 1% Phenol
3. White Lotion NF -see previous notes
-must add “stink" to the "zinc" in order to obtain fine
particles as the precipitate

Suspending Agents
• Categorize by:
– Rheologic Behavior
– Ionic Charge
– Amount used
– Internal or External
– Stable pH range
– Any incompatibilities

Examples of Suspending Agents
• Gums and Derivatives
– Acacia
– Tragacanth
– Pectin
– Carbopol
• Clays
– Bentonite
– Veegum

Examples of Suspending Agents
• Cellulose Derivatives
– Methylcellulose
– Carboxymethyl Cellulose Sodium



• Definition -system of 2 immiscible materials,

one of which is dispersed in globular form
throughout the other

• Terms:
– Dispersed Phase—Various droplets,
discontinuous phase
– Continuous Phase—Carries the dispersed
– O/W Emulsion—Oil is the dispersed phase;
water the continuous phase
– W/O Emulsion—Water is the dispersed
phase; oil is the continuous phase
Why Use Emulsions?
• 1. Permits administration of liquid drug in form of
tiny globules rather than in bulk
• 2. 0/W emulsion if oil tastes offensive
• 3. Irritating medicinal agents to be applied externally
onto the skin (i.e. lotion or cream)—keep in
friendly environment
• 4. 0/W vs. W/0 for topical preparations
W/O—Spreads more evenly on unbroken but
damaged skin to protect (i.e. Water-proof
O/W—Easily removed from skin

To Maintain a Stable Emulsion
• 1. Reduce interfacial tension between the 2
immiscible liquids by using SAA (wetting agent)
• 2. Emulsifying agent must be amphiphilic (SAA)
• 3. There must be a high interaction energy between
the non-polar portions. These London
attractive forces increase the tensile strength of
the film, making it more difficult to break (tough
and pliable)
--SAA forms a film at interface
a. prevents coalescence of the droplets of
b. stabilizes the emulsion
London dispersion forces

Nonpolar tail


Polar head

Emulsions for Internal Use
• Use O/W type
• Acacia is best emulsifying agent for internal use
• Desirable properties of an emulsifying agent
– Non-toxic (GRAS listed)
– NO therapeutic activity
– Amphiphilic structure
– High HLB value (i.e. 8 to 18)

Emulsions for External Use
• O/W or W/O types
• Use soaps as the emulsifying agents
– Monovalent soaps
• Na+ and K+ — Water soluble; Forms O/W
– Divalent soaps
· Ca++ soaps or long chain fatty acids —
Water insoluble; Forms W/O

Stability of Emulsions

• Stability is characterized by:

1. Absence of coalescence—No forming of
one droplet from two droplets
2. Absence of creaming (Phase
3. Nice color
4. Pleasant odor
5. Esthetic appearance
Stability of Emulsions
• 1. Flocculation and Creaming (Measure of Stability)
- flocculation and concentration of globules
- reversible – shake or agitate
- related by Stoke's Law –Density difference, viscosity
a.) upward creaming—O/W
b.) downward creaming—W/O
• 2. Coalescence and Breaking
--irreversible—poor formulation; possibly increase emulsifier
Key is to prevent breaking—dictated by proper
choice and level of emulsifying agent(s)
• 3. Phase Inversion
--must be controlled – often results in finer dispersed phase
--O/W to W/O (Internal Phase becomes External Phase)
Stability of Emulsions
• Na Stearate (o/w) + CaCl2

• Ca Stearate (w/o)

• What is the emulsifying agent?

o o


o o


o 65
Preservation of Emulsions
• Growth of microorganisms cause:
--Physical phase separation — Partitioning
--Discoloration — Turns white or brown
--Gas emission (possibly)
--Odor formation
--Changes in rheological properties

• Microorganisms degrade the emulsifying agent

• Use Preservatives -- Essential
--i.e. Methylparaben and Propylparaben

Emulsion Technology
• Industrial Homogenizers
--In pharmacy practice, use mortar & pestle
• Continental (Dry Gum) Method
Emulsifying agent + Oil—Then add water
[General Rule: 4:2:1 (Oil:Water:Gum)]
-- Acacia + Oil, triturate, then add all water & mix
-- Use ceramic M&P—More friction generated
-- Requires about 3 minutes
-- Can use electric mixer or blender
• English (Wet Gum) Method
Emulsifying Agent + Water—Then add oil
(A thicker preparation—Add oil slowly)
Hand homogenizer

High shear homogenizer

Examples of Official Emulsions

• Castor Oil Emulsion—Laxative

• Hexachlorophene Cleansing
• Mineral Oil Emulsion—Laxative
• Simethicone Emulsion—Gas,
Other Emulsifying Agents
• Anionic
– Alkali Soaps (RCOO- + monovalent)
– Metallic Soaps ((RCOO)2 + di or tri valent)
– Soaps of Organic Amines
– Sulfated Compounds (R-OSO3Na)
– Sulfonates (R-SO3Na)
• Cationic
– Quaternary ammonium compounds
Other Emulsifying Agents
• Non-Ionic (generally esters – R-COOR1)
– Polyethylene glycol 400 monostearate
– Sorbitan monopalmitate (Span 40)
– Sorbitan monooleate (Span 80)
– Polyoxyethylene sorbitan monooleate (Tween 80)
– Polyoxyethylene sorbitan monolaurate (Tween 20)
– Silicones:
• Low MW; have surfactant properties
• High MW; have antifoaming action

• Natural and Modified Natural

– Alginates
– Cellulose derivatives
– Gums (Acacia, Tragacanth, Pectin)
– Lipids (Lecithin)
Surface Tension and

Surface Tension
• Surface Tension is the
– inward force or stress or tension that tends to pull
molecules into the liquid.
– force per unit area at the surface of the liquid which
opposes expansion of the surface (dyne/cm or erg).
• Surface Tension is the term used when we have an
interface of a liquid or solid with air
• Surface Active Agents—Concentrate at the surface
and reduce the ST of the liquid
(Note: Electrolytes (NaCl, KCl) tend to concentrate in the bulk
of the medium and cause an increase in ST)

Surface Tension Example
• Surface tension and interfacial tension
are important considerations in
pharmaceutical technology.
• Consider a beaker of liquid as being a A
beaker-full of molecules. Molecules at
the surface behave differently than
those in the interior of the liquid.
• Molecule A in the interior is completely
surrounded by identical molecules.
• These molecules are oriented in such a
way that there are no residual forces.
• Molecules surrounding A exert equal
forces in all direction and there is no
tendency for molecules to be pulled
one way or the other
• With molecule B at the surface, the
situation is different.
• The molecules in the interior of the
liquid tend to pull B into the interior

Surface Active Agents - Basic

• Amphiphilic Molecules
– Contain polar and non-polar portions
– Are oriented at the surface and significantly
effect ST
– Are not completely hydrophobic or hydrophilic
– Soluble in water and in oil
– Must be a balance between the polar and non-
polar moieties for the molecule to be an
effective SAA
Sodium Lauryl Sulfate

Interfacial Tension

• Definition: The force per unit length at the interface between 2

immiscible liquids (Usually an emulsion in pharmacy)
• Force measured with the Du Nuoy Tensiometer (dynes/cm)
• An INTERFACE is a boundary between two phases
• I.T.—Determines miscibility of liquids
• Examples:
– Water/liquid paraffin—IT = 57 dynes/cm (completely immiscible)
– Water/ether—IT = 10.7 dynes/cm (partially miscible)
– Water/alcohol—IT = 0 dynes/cm (completely miscible)
THUS: To improve miscibility of systems, we must lower the I.T.
HOW? Use Surface Active Agents (Surfactants)
Surfactants at the interface

Schematic of a Surface Active

Properties of Surfactants
• Surfactants may be described variously by
a number of different titles depending
upon how they are used
• 1. Detergents
• 2. Wetting Agents
• 3. Solubilizers
• 4. Emulgents

• See Examples of Surfactants Given

Earlier 80
The HLB System
• Developed for and is important in surfactant
selection for emulsions, etc.
• The Hydrophilic-Lipophilic Balance System (HLB)
• System is based on the knowledge that all surfactants combine
both lipophilic and hydrophilic groups in the molecule
• The proportion of the weight percentages of these two portions
will determine the physical behavior of the surfactant.
• Particularly applies to non-ionic surfactants
• The ratio determines their relative oil-soluble and water-soluble
• The balance between these two tendencies is the Hydrophilic-
Lipophilic Balance.
• Indicates the relative size and strength of the two portions of the
• In the HLB system each surfactant is assigned a numerical value
which is known as its HLB
HLB System
• In general:
--Empirical Scale(1-20 or 1-30) to describe the
properties of non-ionic surfactants
--Below 9—Lipophilic
--Above 11—Hydrophilic
• Function:
1 -3 Antifoaming
4 -6 W/O emulgent
7 -9 Wetting agent
8 -18 O/W emulgent
13 -15 Detergent
10- 18 Solubilizer
• The ability of surfactants to increase the solubility of substances
which normally only have limited solubility in the dispersion medium
• Surfactants are usually non-ionic and dispersion medium is water
• Known as micellar solubilization
• Used to bring into aqueous dispersion a wide range of substances
which are normally considered to be water insoluble

• Mechanism of Solubilization
• Non-ionic surfactants act as solubilizing agents because of their
ability to form micelles
• Micelles are also formed by ionic surfactants as well but these are less
extensively used in solubilization (pharmaceutically)
• We showed earlier that when we add a surfactant to water it forms a
monomolecular layer on the surface of the water
• That is, it concentrates at the interface because it is surface-active

Mechanism of Solubilization,
• Once the surface of the water has been covered by this
monomolecular film the bulk of the solution then becomes saturated
with the surfactant. When saturation has been achieved the surfactant
which up to this time has been in the monolayer form begins to form
molecular aggregates.
• That is, as the concentration of the surfactant is increased the surface
becomes covered, then, the solution becomes saturated and finally
molecular aggregates begin to form.
• These colloidal aggregates are known as micelles.
• The molecules making up the micelles may be arranged in either a
spherical or in a laminar or palisade form.
• All micelles have a hydrophobic core and hydrophilic exterior.
• Micelles are separate and distinct entities from the dispersion

Schematic of Micelle
Surfactant placed in water,
hydrophilic heads orient to
outer water phase and long
chain hydrophobic tails
orient together.

Critical Micelle Concentration
• Definition: The concentration of the surfactant at which the
micelles begin to form
• The CMC is usually characterized by a distinct change in the
physical properties of the solution.
• For example
– 1. Surface tension
– 2. Conductivity
– 3. Osmotic pressure
• Have a change in these parameters as a function of concentration.
• A surfactant or surface active agent will concentrate at the surface
of liquid and reduce the surface tension of the liquid.
• As the concentration of SAA is increased there is a steady
reduction in S. T. until the CMC is reached (See illustration).
• At this point with further increases in concentration there is no
further reduction in surface tension.
• THUS, the point of lowest surface tension is the CMC. When no
more molecules of surfactant can align themselves on the surface
there is no further reduction in surface tension. Further addition of
surfactant will result in the formation of micelles. 86
Surface Tension and CMC

• At CMC, surface tension does not decrease anymore

• ST is experimentally determined by a Du Nuoy
Tensiometer 87
• Since the micelle core is essentially a paraffin-like
region it is capable of dissolving oil-soluble
• The process of dissolving water-insoluble
substances into solution by incorporating them into
micelles is known as solubilization.

Applications of Solubilization
• To improve chemical stability
– Vitamin A less readily oxidized in the solubilized form
– The polar or hydrophilic head of the micelle provides
protection by preventing the OH- ion which catalyzes
oxidation or hydrolysis from reaching the chemical to be
• To improve drug absorption
– Improvement orally and through the skin
• To improve solubility
– Vitamin A and D can be solubilized to give a water-
dispersible mixture that can be added to children’s
• To reduce irritation
– Preparation of Iodophors
• A solution of iodine in a surfactant (decreased irritation,
odor) 89
Wetting Agent
• A surfactant that when dissolved in water,
lowers the advancing contact angle and
aids in displacing air from surface with
liquid phase. (complete wetting vs.
insufficient wetting)

Natural Surfactants
• In the GI Tract:
– Bile salts
• Deoxycholic Acid
• Chenodeoxycholic Acid
• Hyodeoxycholic Acid
• Cholic Acid
– Purpose:

Natural Surfactants
• In the lung
– Mixture of phospholipids, proteins and lipids
– Purpose:

Exosurf Neonatal is a protein-free synthetic lung surfactant that dramatically
reduces mortality and morbidity in premature infants suffering from,
or at risk of, Respiratory Distress Syndrome (RDS) due to surfactant deficiency.
Exosurf Neonatal is effective in the treatment of premature infants
suffering from or at the risk of, Respiratory Distress Syndrome (RDS)
due to surfactant deficiency. (GSK)

Each 10mL vial contains:

DPPC 108mg
Cetyl Alcohol 12mg
Tyloxopol 8mg
NaCl 47mg
HCl/NaOH to adjust pH

Reconstitute with 8mL SWFI

pH = 5-7
Osm = 185 mOsm/L

Natural Surfactants
• In the Eye
– Cornea – Tear Interface

– Aqueous Tear Film

– Surface of Tear Film

– Tear Film