Lecture 6:

Colloidal Dispersed System

Physical Pharmacy II
Zainab A. Radhi
Assistant Lecturer in pharmaceutics

Class: 2nd year

Baghdad College of Medical Sciences

Outlines

• Introduction

• Colloidal Systems

• Types of Colloidal Systems

• Properties of Colloids
 Introduction
Dispersed systems consist of a dispersed phase which is distributed
throughout a continuous phase or dispersion medium.

The dispersed material may range in size from particles of atomic and
molecular dimensions to particles whose size is measured in millimeters.

Based on the size of the dispersed phase, the dispersed systems can be
classified into three types:

(a) Molecular dispersions

(b) Colloidal dispersions

(c) Coarse dispersions

Class Particle size* Characteristic of system Examples

Molecular <1 nm  Invisible in electron microscope Oxygen molecules,

dispersion  Pass through ultra-filter and semipermeable ordinary ions, glucose
membrane
 Undergo rapid diffusion

Colloidal 1 nm -0.5 µm  Not resolved by ordinary microscope Colloidal silver sols,

dispersion  Visible in electron microscope natural and synthetic
 Pass through filter paper polymers, cheese, butter,
 Do not pass semipermeable membrane jelly, paint, milk,
 Diffuse very slowly shaving cream, etc.

Coarse > 0.5 µm  Visible under microscope Grains of sand, most

dispersion  Do not pass through normal filter paper pharmaceutical
 Do not dialyze through semipermeable emulsions and
membrane suspensions, red blood
 Do not diffuse cells

* 1 nm (nanometer) = 10-9 m; 1 µm (micrometer) = 10-6 m.

Diffusion through a semipermeable membrane
Because the size of colloidal particles, they can be separated from
molecular particles by the use of semipermeable membrane. This
technique is known as Dialysis.

Conditions on the two sides, A and B, of

the membrane are shown at the start and
at equilibrium. The white circles are the
colloidal particles that are too large to
pass through the membrane. The small
dots are the electrolyte particles that pass
through the pores of the membrane.

• Dialysis occurs in vivo; thus, ions and small molecules pass readily

from the blood, through a natural semipermeable membrane, to the

tissue fluids; the colloidal components of the blood remain within the
capillary system.

• The principle of dialysis is

utilized in the artificial kidney,

which removes low–molecular-
weight impurities from the
body by passage through a
semipermeable membrane.
Types of Colloidal Dispersions:
(According to the type of dispersed phase and dispersion medium)
Dispersion Dispersed Phase Colloid Type Examples
Medium
Solid Solid Solid sol Pearls, opals

Solid Liquid Solid emulsion Cheese, butter

Solid Gas Solid foam Pumice, marshmallow

Liquid Solid Sol, gel Jelly, paint

Liquid Liquid Emulsion Milk, mayonnaise

Whipped cream,
Liquid Gas Foam
shaving cream
Gas Solid Solid aerosols Smoke, dust

Gas Liquid Liquid aerosols Clouds, mist, fog

Note : a gas in gas always produce a solution

Types of Colloidal Dispersion
(According to the shape of dispersed particles)
• The shape adopted by particles in dispersion is important because the

more extended the particle, the greater is its specific surface and the
greater is the opportunity for attractive forces to develop between the
particles of the dispersed phase and the dispersion medium.

• specific surface is defined as the surface area per unit weight or volume

of material.

• The possession of a large specific surface results in many of the unique

properties of colloidal dispersions.

Some shapes of sphero-colloids and fibrous colloids are shown :

Types of Colloidal Systems

(According to the interaction between the dispersed phase and
dispersion medium)
They are classified on the basis of the interaction of the molecules of the
dispersed phase with the molecules of the dispersion medium into:
1. Lyophilic Colloids (solvent-loving): are systems containing colloidal
particles that interact with the dispersion medium, due to their the
affinity for the dispersion medium.

Thus such materials form colloidal dispersions, or sols easily. Thus,

lyophilic colloidal sols are usually obtained simply by dissolving the
material in the solvent being used. For example, the dissolution of
acacia or gelatin in water leads to the formation of a sol.
The various properties of this class of colloids are due to the attraction
between the dispersed phase and the dispersion medium, which leads to
solvation (the attachment of solvent molecules to the molecules of the
dispersed phase).

Most lyophilic colloids are organic molecules, and according to the

solvent used in these systems, it can be divided into:

Hydrophilic colloids, in which water is the

dispersion medium, where hydration occurs. For
example: gelatin, acacia, insulin, albumin
produce hydrophilic sols.

Lipophilic colloids, in which the dispersion

medium non-aqueous, organic solvents. For
example: rubber and polystyrene form lipophilic
colloids in nonaqueous, organic solvents.

Thus the term lyophilic has meaning only when applied to the material
dispersed in a specific dispersion medium. A material that forms a lyophilic
colloidal system in one liquid (e.g., water) may not do so in another liquid
(e.g., benzene).

One of the most important property of

lyophilic colloid is the presence of
solvent sheath.
2.Lyophobic Colloids (solvent-hating): This class of colloids is composed
of materials that have little attraction, if any, for the dispersion medium.

Their properties differ from those of the lyophilic colloids due to the
absence of a solvent sheath around the particle.

Lyophobic colloids are generally composed of inorganic particles dispersed

in water. Examples of such materials are gold, silver, sulfur, arsenous
sulfide, and silver iodide. Gold Colloids
in Water

In contrast to lyophilic colloids, it is necessary to use special methods to

prepare lyophobic colloids.

3.Association Colloids (Amphiphilic colloids): These colloids contain

amphiphilic molecules or ions, when present in a liquid medium at low
concentrations, these amphiphiles exist separately and are of such a size
as to be subcolloidal, as the concentration is increased, to the critical
micelle concentration (CMC), micelles are formed (they may contain 50
or more monomers); micelles lie within the colloidal size range because
the diameter of each micelle is about of 50 Å (5 nm) which is within the
size range of colloidal particles.
  Solubilization is an important property of association colloids in
solution; it is a phenomenon that can be described as the ability of the
micelles to increase the solubility of materials that are normally
insoluble or slightly soluble in the dispersion medium.

 It is important to know the location, distribution, and orientation of

solubilized drugs in the micelle. The location of the solubilized
molecule (solubilizate) in a micelle is related to the balance between
the polar and nonpolar properties of the molecule, and also related
to the chemical nature of the solubilizate.

• The nonpolar molecules in aqueous systems of surface-active

agents would be located in the hydrophobic core of the micelle.

Polar part of micelle Non-polar

solubilizate

Non-polar part of micelles

• Whereas polar molecules would tend to be adsorbed onto the micelle

surface (polar part).
• Polar–nonpolar molecules would tend to align themselves in an
intermediate position within the surfactant molecules forming the
micelle.
Amphiphilic
solubilizate

Note: Nonionic surfactants are of most pharmaceutical interest as

solubilizing agents because of their lower toxicity.

Lyophilic Lyophobic Association (Amphiphilic)

Dispersed phase Dispersed phase ordinarily Dispersed phase consists of
consists generally of consists of inorganic aggregates (micelles) of small
large organic molecules particles, such as gold or organic molecules or ions
lying within colloidal silver whose size individually is
size range below the colloidal range
Molecules of dispersed Little if any interaction Hydrophilic or lipophilic
phase are solvated, i.e., occurs between particles portion of the molecule is
they are associated with and dispersion medium solvated, depending on
the molecules (no solvation) whether the dispersion
comprising the medium is aqueous or
dispersion medium nonaqueous
Molecules disperse Material does not disperse Colloidal aggregates are
spontaneously to form spontaneously, and special formed spontaneously when
colloidal solution procedures therefore must the concentration of
be adopted to produce amphiphile exceeds the
colloidal dispersion critical micelle concentration
Continued in the next slide
Connected to the previous slide
Lyophilic Lyophobic Association (Amphiphilic)
Viscosity of the dispersion medium Viscosity of the dispersion Viscosity of the system
ordinarily is increased greatly by medium is not greatly increases as the
the presence of the dispersed increased by the presence of concentration of the
phase; at sufficiently high lyophobic colloidal particles, amphiphile increases, as
concentrations, the sol may which tend to be unsolvated micelles increase in number
become a gel; viscosity and gel and symmetric and become asymmetric
formation are related to solvation
effects and to the shape of the
molecules, which are usually
highly asymmetric

Dispersions are stable generally in Lyophobic dispersions are In aqueous solutions, the
the presence of electrolytes; they unstable in the presence of critical micelle
may be salted out by high even small concentrations of concentration is reduced by
concentrations of very soluble electrolytes; effect is due to the addition of electrolytes;
electrolytes; effect is due primarily neutralization of the charge salting out may occur at
to desolvation of lyophilic on the particles; lyophilic higher salt concentrations
molecules colloids exert a protective
effect

Properties of Colloids
1.Optical Properties

The Faraday–Tyndall Effect: This effect occurs when a strong beam of

light is passed through a colloidal sol; a visible cone is formed as a result
of the scattered light by the colloidal particles.
 2.Kinetic Properties: Several properties of colloidal systems are related
to the motion of particles with respect to the dispersion medium:

1-Thermally induced

a) Brownian movement

b) Diffusion

c) Osmosis

2- Gravitationally induced: (Sedimentation)

3- Applied externally: (Viscosity)

4- Electrically induced motion

1-Thermally induced (increased by increasing temperature)

a) Brownian motion: It describes the random movement of colloidal
particles. The erratic motion, resulting from the bombardment (collisions)
of the particles by the molecules of the dispersion medium. The motion of
the molecules cannot be observed, because the molecules are too small to
see.

 The velocity of the particles increases

with decreasing particle size.
 The velocity of the particles decreases
with increasing the viscosity of the
medium and the motion finally stops.
b) Diffusion: Particles diffuse spontaneously from a region of higher
concentration to one of lower concentration until the concentration of
the system is uniform throughout. Diffusion is a direct result of
Brownian movement, therefore (all factors affect Brownian movement
will affect diffusion).

According to Fick's first law, the amount

(dq) of substance diffusing in time (dt)
across a plane of area (S) is directly
proportional to the change of concentration,
dc, with distance traveled, dx.

Fick's law is written as: 𝑑𝑐

dq = - DS dt
𝑑𝑥
D is the diffusion coefficient, the amount of
material diffusing per unit time across a unit
area when the concentration gradient
(dc/dx), is unity.

It is normal for the concentration curve to increase or decrease sharply at the boundaries of
the barrier because, in general, C1 is different from Cd, and C2 is different from Cr
 𝒈/𝒄𝒎 𝟑
g = - D cm2 sec →→ D = cm2 / sec. (Units)
𝒄𝒎

D thus has the dimensions of area per unit time.

Note: the Negative sign denotes that diffusion takes place in

the direction of decreasing concentration.

Cd Cr

 The passage of a substance may be through porous membrane or

through tortuous pores or channels (example. Skin)

 Smaller particles diffuse faster in a given media.

Molecular > colloid > coarse

 Passive diffusion caused by a concentration gradient and carried out

through Brownian motion.

 It is important for the release of drug from topical preparation and in the

GIT absorption of drugs.

c) Osmosis: It is the action in which only the solvent is transferred, while
the diffusion involve the passage of solute.
Osmotic pressure: is the pressure that results from osmosis. All aqueous
solutions of nonvolatile solutes exert an osmotic pressure.
The osmotic pressure, π, of a dilute colloidal solution is described by the
van't Hoff equation:
C: molar concentration of solute
π = cRT R: gas constant = 0.082 atm.mole/ L.deg
T: absolute temperature in Kelvin

This equation can be used to calculate the molecular weight of a colloid in

a dilute solution.

Importance of calculation the osmotic pressure

1- For ideal solution
Since the molar concentration represents the grams of solute per liter of
solution divided by the molecular weight.
So we can replace c with cg/M in the above equation in which cg is
grams of solute per liter of solution and M is the molecular weight , we
obtain: 𝑪𝒈 𝝅 𝑹𝑻
π= RT →→ =
𝑴 𝑪𝒈 𝑴

This equation is used to calculate the molecular weight of substance in

an ideal, very dilute spherocolloid.

(Home work): A sample of albumin in an aqueous solution at conc. Cg= 3.2 g/l was
placed in osmometer at 28°C. its osmotic pressure was found to be 0.00112 atm
what is the Mwt of albumin . assuming the solution is sufficiently dilute.
(Ans: Mwt = 70520 g/mole)
2- For real solution
The osmotic pressure can give us idea about molecular weight of a colloid
and to determine the degree of solute – solvent interaction as following:
π 1
= RT ( + B Cg) →→
Cg 𝑀
π 𝑅𝑇
= + RT B Cg It is a straight line equation
Cg 𝑀
↓ ↓ ↓ ↓
y- axis intercept slope x- axis

B is a constant for any particular solvent/solute system and depends on

the degree of interaction between the solvent and the solute molecules.

↑ B mean ↑ interaction between the solvent and the solute

The intercept is RT/M, and if the temperature is known, the molecular

weight of the solute can be calculated.
A plot of π/cg against cg generally results in one of three lines depending
on whether the system is:
ideal (line I) or real (lines II and III).
• In lines II and III, the slope of the line is B,
the interaction constant.
• In line I, B equals zero and is typical of a
dilute ideal spherocolloidal system.
• Line III is typical of a linear colloid in a
solvent having a high affinity for the
dispersed particles.

The solvent of line III colloidal dispersion is referred to as a “good” solvent for
that particular colloid. There is a marked deviation from ideality as the
concentration is increased and B is large.
2- Gravitationally induced
Sedimentation: occurs when aggregates of colloidal particles separate
from the continuous phase and settle to the bottom as these aggregates
are denser than the liquid.

The velocity, v, of sedimentation of spherical particles having a density ρ

in a dispersion medium of density ρ0 and a viscosity η0 is given by
Stokes's law:
r = radius of paticle
V = 2r2 ( ρ –ρ0) g ρ = density of particle
ρ0 = density of the dispersion medium
9 η0
η0 = viscosity of the dispersion medium
g = is the acceleration due to gravity

Factors affecting sedimentation

- Particle size ( ↓ particle size → ↓ sedimentation )
- Viscosity ( ↑ viscosity → ↓ sedimentation)
Difference between the densities of the dispersed particles and the dispersion
medium ( ↑ difference → ↑ sedimentation )
If the particles are subjected only to the force of gravity, then the lower

size limit of particles obeying Stokes's equation is about 0.5 µm, so

when the particles size <0.5 µm and are subjected only to the force of

gravity, they would not obey Stokes law, because Brownian movement

becomes significant and tends to offset (counter-balance)

sedimentation due to gravity and promotes mixing instead.

• Consequently, a stronger force must be applied to bring about the

sedimentation of colloidal particles in a quantitative and measurable

manner, this is accomplished by use of:

A stronger force (ultracentrifuge) must

be applied to bring about the
sedimentation of colloidal particles, this
can produce a force one million times
that of gravity.

In a centrifuge, the acceleration of

gravity (g) in Stokes law is replaced by
angular acceleration (ω2x).
3- Applied externally

Viscosity: is an expression of the resistance to flow of a system under an

applied stress. The more viscous a liquid is, the greater is the applied
force required to make it flow at a particular rate.

Viscosity study can give us information about:

The shape of particles in dispersion.

The molecular weight of the dispersed phase.

The shape of particles in dispersion

The shapes of particles of the disperse phase affect the viscosity of
colloidal dispersions. Sphero-colloids form dispersions of relatively
low viscosity, whereas systems containing linear particles are more
viscous. The relationship of shape and viscosity reflects the degree of
solvation of the particles. If a linear colloid is placed in a solvent for
which it has a low affinity, it tends to “ball up,” that is, to assume a
spherical shape, and the viscosity falls. This provides a means of
detecting changes in the shape of flexible colloidal particles and
macromolecules.
 The molecular weight of the dispersed phase

Einstein developed an equation of flow applicable to dilute colloidal

dispersions of spherical particles:

η0: viscosity of the dispersion medium

ɳ = ɳ0 (1+2.5 φ)
η: viscosity of the dispersion
φ: volume fraction of colloidal particles in
dispersion

The volume fraction is defined as the volume of the particles divided

by the total volume of the dispersion; it is therefore equivalent to a
concentration term.

• Both η0 and η can be determined using a capillary viscometer.

 Several viscosity coefficients can be defined with respect to this equation.
Such as relative viscosity (ηrel), specific viscosity (ηsp) :
𝜂
η rel = =1+2.5φ
𝜂0

ηsp = ηrel - 1 = 2.5φ

ηsp
= 2.5 ≈ (constant)
𝜑

Because φ is directly related to concentration:

ηsp ηsp
= = K (constant) (Dilute solution)
𝜑 𝑐

c = concentration in % w/ v

ording to the so-called Mark–Houwink equation

By determining η at various concentrations and knowing η0, one can

calculate ηsp from equation .

If ηsp/c is plotted against c and the line extrapolated to infinite dilution, the
ηsp/c cm3/g

intercept is k1 . This constant, commonly known as the intrinsic viscosity,

[η], is used to calculate the approximate molecular weights of polymers.

[η] = KM a
where K and a are constants characteristic
of the particular polymer–solvent system.
These constants, which are virtually
independent of molecular weight.
Example: Compute the molecular weight of a cellulose nitrate fraction
were K= 4x10 -5, a = 0.99 at 27°C , [η]= 2.4

[η]= KMa

2.4 = 4 x 10 -5 x M 0.99
H.W: 1% solution of certain
We take the log to the equation:
polymer with Mwt=1.325 x10 5
log [η]= log K + a log M K= 1.445 x10 – 4 , a= 0.93
calculate [η]
log 2.4 = log 4x 10-5 + 0.99 log M
(Answer:- [η]= 8.38)
0.38 = -4.398 + 0.99 log M

4.778= 0.99 logM

Log M=4.826

M=67028

4- Electrically induced motion

It is the movement of charged surface with respect to an adjacent

liquid phase. One of the most important application for such
movement is the electrophoresis.

Electrical Properties are affected by the presence of a charge on the

surface of a particle.
 Pharmaceutical Applications of Colloids
Colloids has been used in many pharmaceutical application, it is
used in modifying pharmaceutical agents properties as drug solubility and
also used in different drug delivery systems.

Examples of drug delivery systems use colloids :

1.Hydrogels: is a colloidal gel in which water is the dispersion medium.

2. Microparticles: are small (0.2–5 µm), loaded microspheres of

natural or synthetic polymers.

Microcapsule Microcapsule with Microsphere with molecular mix

with core nanodomaines of matrix polymer and drug

3. Liposomes: consist of an outer uni- or multi-laminar membrane

and an inner liquid core.
4. Microemulsions: are excellent
candidates as potential drug delivery
systems because of their improved drug
solubilization, long shelf life, and ease of
preparation and administration.

5. Polymeric micelles: are structures

similar to liposomes but do not have an
inner liquid compartment.

6. Nanocapsules are submicroscopic colloidal drug carrier systems

composed of an oily or an aqueous core surrounded by a thin polymer
membrane.