Pharmaceutical Colloidal Dispersion

Subject: Physical Pharmaceutics-II
Subject code:BP403T
UNIT 1 :Colloidal dispersions
Presented by
(Dr) Kahnu Charan Panigrahi
Asst. Professor, Research Scholar,
Roland Institute of Pharmaceutical Sciences,
(Affiliated to BPUT)
Web of Science Researcher ID: AAK-3095-2020
12/14/2021 KC PANIGRAHI 1

• Colloidal system is a dispersion
where the dispersed phase are
distributed uniformly in dispersion
medium(External/continuous
Phase).
• Particle size-From 1nm to 0.5 µm
• In colloidal systems particles pass
through filter paper but do not
pass through the semipermeable
membrane.
INTRODUCTION

4
Class Particle Size* Characteristics of System
Molecular dispersion Lessthan 1nm Invisible in electron microscope
Passthrough ultrafilter and semipermeable
membrane
Undergo rapid diffusion
Colloidal dispersion From 1nm to 0.5 µm Not resolved by ordinary
microscope (although
may be detected under
ultramicroscope)
Visible in electron
microscope
Passthrough filter paper
Do not pass
semipermeable
membrane
Diffuse very slowly
Coarse dispersion Greater than 0.5µm Visible under microscope
Do not pass through
normal filter paper
Do not dialyze through
semipermeable
membrane
Do not diffuse
Classification of dispersed system

TYPES OF COLLOIDAL SYSTEMS
Dispersion
medium
Dispersed
phase
Examples
Solid Solid ZnO Paste
Solid Liquid Butter
Solid Gas Solid foam, Pumice
Liquid Solid Bentonite magma sol
Liquid Liquid Soyabean water
emulsion
Liquid Gas Foams,shaving cream
Gas Solid Solid aerosol
Gas Liquid Liquid aerosol

TYPES OF COLLOIDS
On the bases of the interaction of the particles, molecules or ions of
the dispersed phase with the molecules of the dispersion medium:
1. LYOPHILIC COLLLOIDS
2. LYOPHOBIC COLLOIDS
3. ASSOCIATION COLLOIDS

LYOPHILIC COLLOIDS
• In this system dispersed particles have a greater
affinity to the dispersion medium (solvent).
• They are also termed as intrinsic colloids.
• The dispersion medium forms a sheath around the
colloidal particles and solvates.
• This makes the dispersion thermodynamically stable.
• Dispersion particle may be hydrophilic (acacia, gelatin)
or lipophillic(rubber, polystyrene)
• Exp: acacia or gelatin in water or celluloid in amyl
acetate solution.

LYOPHOBIC COLLOIDS
• These are the dispersion that have little attraction
(solvent hating), is possible between the dispersed
phase and dispersion medium.
• These are also referred as extrinsic colloids.
• This is due to primarily the absence of a solvent sheath
around the particles
• These are stable because of the presence of a charge
on particles.
• When water is used as solvent this is called hydrophobic
colloid.
e.g. gold, silver, sulfur in water

PREPARATION OF LYOPHOBIC COLLOIDS
1.Dispersion Method: Reduced the particle size of the
coarse particles
a. Milling and grinding method:
• Size reduction was performed using colloidal mill.
• It consists of two metallic discs nearly touching each
other and rotating in opposite directions at a very high
speed about 7000 revolution per minute.
• The space between the discs of the mill is so adjusted
that coarse suspension is subjected to great shearing
force giving rise to particles of colloidal size.
e.g. colloidal kaolin and zinc oxide

b. Peptization:
• The process of converting a freshly prepared precipitate into
colloidal form by the addition of suitable electrolyte is called
peptisation.
• Cause of peptisation is the adsorption of the ions of the
electrolyte by the particles of the precipitate.
• The electrolyte used for this purpose is called peptizing agent or
stabilizing agent.
• Eg. Glycerin, sugar, lactose, citric acid etc.
c. Electric arc method:
• This method is used to prepare sols of platinum, silver, copper
or gold.
• In this method an intense electric arc is produced between two
metal electrode in cold water.
• The tremendous heat generated by this method give colloidal
solution.

2. Condensation method
In condensation method, the smaller particles of the
dispersed phase are aggregated to form larger particles of
colloidal dimensions.
Some important condensation methods are described below:
a)Excessive cooling: Solutions of mercury and sulphur are
prepared by passing their vapours through a cold water
containing a suitable stabilizer such as ammonium salt or
citrate.
b)Exchange of solvent: Colloidal solution of sulphur,
phosphorus which are soluble in alcohol but insoluble in
water can be prepared by pouring their alcoholic solution in
excess of water.

ASSOICATION COLLOIDS
• In this system certain molecules or ions called
amphiphiles or surface active agents having two distinct
regions of opposing solution affinities within the same
molecule or ion.
• These colloids behave as normal electrolytes at low
concentrations but behave as colloids at higher
concentrations.
• These associated colloids are also referred to as micelles.
• Sodium stearate (C18H35NaO2)behave as electrolyte in
dilute solution but colloid in higher concentrations.
Examples: Soaps , higher alkyl sulphonates , polythene
oxide.

COLLOIDAL SOLUTION PROPERTIES:
• Electrical properties
• Optical properties
• Kinetic properties

Electrical properties
Surface charge – zeta potential :-
• Let’s consider solid particle are dispersed in an aqueous
solution containing electrolyte .
• Distribution of charges are shown in the fallowing fig.
• Assuming the cation are absorbed at interface

The interface:
• aa’ the actual plane is the solid liquid interface and it is
assumed that the cation are adsorbed in the interface and
impart +ve charges.
Tightly bound layer:
• Immediately adjacent to the interface aa’ is the region of
tightly bound layer and it extend up to bb’.
• Once the adsorption is complete the cation attract few
anion and repel the approaching cation.
• Thus at equilibrium some excess anion are present at this
region however their number is less than adsorbed cation.
Therefore bb’ the shear plane still impart +ve charge.
• The degree of attraction of certain molecule and counter
ion is such that shear plane is bb’ rather than aa’.

Diffused 2nd layer:
• This is the region bound by the line bb’ and cc’.
• In the layer excess –ve ion are present.
• At and beyond cc’ the charge is electrically neutral.
• As a whole the system is electrically neutral.
• Thus the electrical distribution at the interface is
equivalent to the double layer which consist of tightly
bound layer and diffused 2nd layer.
• When the interface adsorbed –ve ion than aa’ is negative,
bb’ is negative and cc’ is neutral.
Nernst potential and zeta potential:
• Nernst potential is the potential at actual surface itself i.e.
aa’ due to presence of potential determining ion. It is
denoted as E and also called electrodynamic potential.

• It is defined as the potential difference between the
actual surface and the electro neutral region of the
solution.
• Zeta potential is the potential observed at the shear
plane i.e. bb’.
• Zeta potential is also known as electrokinetic
potential.
• It is defined as the potential difference between
surface of tightly bound layer or shear plane and
electroneutral region.
• Zeta potential also defined as the work required to
bring unit charge from infinite to surface of particle.
• The zeta potential is more important than nernst
potential.

Electrophoresis:-
• The principle of electrophoresis is used determined
the sign and the magnitude of the Zeta potential .
• Electrophoresis involve the moment of a charge
particle through a liquid under the influence of an
applied potential difference.
• An electrophoresis cell is fitted with two electrodes.
• The dispersion is introduce into the cell and when a
potential difference is applied across the electrode
particle migrate towards oppositely charged
electrodes.

• If the particle move towards anode charge on the particle
is negative. Thus the sign of zeta potential can be
identified.
• The rate of migration is a function of the amount of charge
on the particle .
• The ultra microscope is used to observe the migration of
the particle.
• The apparatus is standardize by the use of particle of
known potential. Rabbit erythrocytes are commonly used
in this purpose.
Velocity of migration of particle (cm/sec) α potential
gradient across the particle (volts)
V α E
V = ς × E
ς = V/E
ς represent Zeta potential

• There are a number of other factors that influence
the migration.
• Therefore the zeta potential of a colloidal system
may be determined by equation.
ς = V/E × 4π 𝔶 /ε
where ε = dielectric constant of the medium.
𝔶 = Viscosity of the medium, poise
Donnan membrane equilibrium:-
• Donnan membrane equilibrium principle is used
to enhance the absorption of drugs such as
sodium salicylate and potassium benzyl penicillin.
• Sodium CMC is not diffusible but enhane
absorption of anionic drug.

The principle of Donnan membrane equilibrium is as
follows:
• A solution of sodium chloride is placed on one side of the
semipermeable membrane.
• On the other side, a solution of negatively charged
colloids together with it’s counter ions is placed.
• The volumes of solution on the two side of the membrane
are considered to be equal.
• This situation is shown in the fig. The vertical line
represents the membrane.

Intial state:
Out side (0) Inside(i)
Na+
Cl- Na+ R-
At equilibrium:
Out side (0) Inside(i)
Na+ Na+
Cl-
Cl- R-
Sodium and Chloride ions move freely across the semi permeable membrane,
but colloidal particles, R- , are not diffusible. Soon equilibrium is attained .

• Apply the condition of electro neutrility i.e. the positive and
negative charges on other side of the membrane must be
balanced accordingly the following equations are written.
Outside: [Na+]0 = [Cl-]0 ...............................(1)
Inside: [Na+]i = [R-]i+[Cl-]i..........................(2)
• According to the principle of escaping tendency of
electrolytes , the concentrations of electrolytes on both
sides of the membrane must be same. Then
[Na+]0 [Cl-]0 =[Na+]i [Cl-]i .....................(3)
• Substituting the terms in equations (1) and (2)
appropriately in equation gives
[Cl-]0 ×[Cl-]0 = [Cl-]i ([R-]i +[Cl-]i)
= [Cl-]i
2 +([R-]i [Cl-]i)
= [Cl-]i
2 (1+[R-]i/ [Cl-]i)
[Cl-]0
2/[Cl-]i
2 =1 + [R-]i/ [Cl-]i
[Cl-]0 /[Cl-]i = ( 1+ [R-]i/[Cl-]i)1/2 .............................. (4)

• Equation (4) represents the Donnan membrane equilibrium
• Equation (4) is useful for calculating the ratio of
concentration of the diffusible ion outside and inside the
membrane at equilibrium.
• Equation (4) demonstrates the use of sodium CMC in order
to enhance the absorption of drugs such as sodium
salicylate .
• CMC is a negatively charged ion and non diffusible , i.e., it
represents [R-].
• The drug salicylate ion is diffusible and negatively charged
ion , i.e., it represents [D-], which is same as that of [Cl-].
• At equilibrium the ratio of diffusible drug , [D-] on either
side of membrane is written in the format of equation (4).
[D-]0/[D-]i =(1+ [R-]i/[D-]i)1/2 ...............................(5)

• Consider the following cases for selecting the
appropriate concentration of the components .
Case 1 : when [R-]i/[D-]i = 8, then [D-]0/[D-]i = 3
Case 2: when [R-]i/[D-]i= 99 then [D-]0/[D-]i= 10
• In case 1, both sodium CMC and drug are present on
the same side , which represent the gastrointestinal
tract (inside).
• If the ratio is 8, the relative amount of drug present on
the in blood (outside), is comparatively 3 times that of
the drug in gastrointestinal tract.
• In case 2 the drug moving out is more when
concentration of non diffusible substance is higher.
• In other words, a dosage form containing high
concentration of sodium CMC will drive away the drug
from the gastrointestinal tract into blood.

Tydal Effect:- When a narrow beam of light is passed
through the ciolloidal dispersion the path of light
become eliminated and can be observed at right angle
using ultra-microscope. This is called Faradey’s Tyndal
Effects.
Ultra-microscope:- In this method the particle
appears as bright spot against the dark back ground.
Electromicroscopy:- Particle size, shape, structure can
be determined using an electromicroscope.
OPTICAL PROPERTIES

Turbidity (Ʈ):
• Turbiity can be used to estimate concentration of
dispersed particles and molecular weight of solute.
Equipments used are
1. Spectrophotometer
2. Nephelometer.
• Spectrophotometer measures the intensity of
transmitted light.
• Turbidity-light intensity relationship is given by
I/Io = e-ƮL
I0 = intensity of incident light
I = intensity of transmitted light
L = length of sample (1 cm)
Ʈ = turbidity

Molecular weight – turbidity relation:
Hc/ τ =1/M +2Bc
τ =turbidity in cm-1 ,
c= concentration of the solute in gm/cm3
M=weight of the average molecular weight, in
g/mol or Daltons

KINETIC PROPERTY
(a) Brownion Motion:-
It is named after Robert Brown who proposed that
colloidal system do not sediment but are in
continuous random motion.
(b) Diffusion:-
• Since the size of colloidal particle is small, they can
diffuse to semi-permeable membrane.
• Diffusion can be expressed by Frick’s First Law
which states that “the particles diffused from the
region of high concentration to the region of low
concentration while equilibrium attained.
• The relationship which is used to determine
molecular weight of polymer is

M=molecular weight
v =specific volume
R= Ideal gas constant
N=Avogadro’s number
ɳ = Viscosity
T= absolute temperature
(c) Viscosity:-
Viscosity of a colloidal system affected by various factor-
●Shape of dispersed particle: Spherical particle impart
relatively low viscosity.
●Affinity of the particle to the medium linear particle have
low affinity to the medium.
●Type of colloid:-Lyophillic colloid have more viscosity than
Lyophobic colloid.
●Higher the molecular weight, greater is the viscosity.

• The flow of dilute colloidal system is expressed
by an equation developed by Einstein.
= o(1+ 2.5 Ǿ)
o= viscosity of the dispersion medium
= viscosity of the dispersion
Ǿ= volume fraction of colloidal particle
• The volume fraction is defined as the volume of
the particles divided by the total volume of
dispersion

(d)Sedimentation:-
• The viscosity of sedimentation of spherical
particle is obtained by Stoke’s Law.
• Ultra-centrifugation is used to study the micellar
properties of drug.
(e)Colligative Property:-
• Only osmotic pressure of dispersion can be used
in order to detect the molecular weight of
dispersed particle.
V= 2r2 (ρ- ρo) g
9

Characteristics of dispersed phase:
1. Particle size:
• This influence colour of dispersion.
• Wavelength of light absorbed α 1/ Radius
• (small wavelength)VIBGYOR (large wavelength)
2. Particle shape:
• Depends on the preparation method and affinity
of
• dispersion medium
• This influence colour of dispersion.
• Shapes- spherical, rods, flakes, threads,
ellipsoidal.
• Gold particles- spherical (red), disc (blue).

3. Surface area:
• Particle size small- large surface area
• Effective catalyst, enhance solubility.
4.Surface charge:
• Positive (+)= gelatin, aluminum.
• Negative (-) = acacia, tragacanth.
• Particle interior neutral,
• surface charged.
• Surface charge leads to stability of
• colloids because of repulsions.

STABILITY OF COLLOIDS:
• Good colloidal dispersions should not change until usage.
• Colloidal dispersion stable (Brownian motion),
unstable (Precipitate)
Stability reasons:
1. Lyophilic – solvent sheath on particles.
2. Lyophobic – Electric charge on particles.
Lyophobic colloids stability:
DLVO theory- Derjaguin, Landau, Verway & Overbeek
• This theory is based on distance between 2 particles
and their interactions
• Colloidal particles exhibit brownian motion causing
collisions between particles.
• Amount of electrolytes control stabilization &
Precipitation.

Particle interactions:
1. Vanderwaals attraction forces:
• Chemical nature
• size of particle
• Attraction curve (Va)
2. Electrostatic repulsive curve:
• Density,
• surface charge
• thickness of EDL
• Repulsion curve (Vr)
• Zeta potential stable range 20-50
mv.
3. Net energy interactions:
• Algebraic additions of 2 curves (Vt)

Conclusions:
1. Primary minimum:
Particles close atomic orbital's overlap Pot.
Energy ↑ Aggregates.
2. Secondary minimum:
Particles separated (1000-2000 A0) Attractions
Aggregates. (Used in controlled flocculation)
3. Net energy peak:
At intermediate distance (3-4A0) Repulsions more
Brownian motion Stable Zeta potential (50 mv)

INSTABILITY OF LYOPHOBIC COLLOIDS:
• Breakage of potential energy barrier leads to
precipitation/ agglomeration.
Instability reasons:
1. Removal of electrolyte: The repulsive force reduces
below critical value result coagulation. This is like
primary minimum in DLVO theory.
2. Addition of electrolyte: This is like secondary
minimum in DLVO theory.
3. Addition of electrolytes of opposite charge: This is
like secondary minimum in DLVO theory.
4. Addition of oppositely charged colloid: This is like
secondary minimum in DLVO theory.

1. Removal of electrolyte
Colloids + electrolytes = stable colloidal dispersion
= Dialysis = remove Electrolytes = Particles coagulate =
Settle to bottom.
2. Addition of electrolyte
Stable colloidal dispersion + excess electrolyte = electrolyte
accumulate = instability
3. Addition of electrolytes of opposite charge
Stable colloidal dispersion + electrolyte opposite charge =
attractions between particles = Flocculation of particles.
Schulze-Hardy Rule: Precipitating power α ionic charge
Al+3>Ba+2>Na+ So4-2>Cl-
4. Addition of oppositely charged colloid
Bismuth colloids (+) + Tragacanth colloids (-) = Coagulation.

INSTABILITY OF LYOPHILIC COLLOIDS:
• Stability – Solvent Sheath
• Instability – aggregation/ precipitation.
Instability reasons:
1. Addition of excess electrolyte
2. Addition of oppositely charged colloid
3. Addition of non-solvent.
Addition of excess electrolyte:
• Electrolyte normal Conc. Zeta potential↓ No Coagulation
• Electrolyte high Conc. ions + water No solvent for sheath
Hofmeister Rank Order:
• States that the precipitating power of an ion is directly related
to ability of that ion to separate water molecule from colloidal
particle.
• Mg+2> Ca+2> Na+ >K+

2. Addition of oppositely charged colloid:
Mixing of lyophillic colloid with oppositly
charged colloid result flocculation.
3. Addition of non-solvent:
Less polar solvent like acetone and alchol have
greater affinity towards water. When these are
added dehydration of lyophillic colloid results to
formation of lyophobic colloid.

Sensitization & Protective colloidal action:
1. Lyophobic colloid + excess electrolyte charge
neutralize Precipitation.
2. Lyophobic colloid + Lyophilic colloid (low Conc)
Sensitization Add electrolyte Precipitation.
3. Lyophobic colloid + Lyophilic colloid (High Conc)
Protective colloid Add electrolyte ions can not
reach particle No Precipitation.
Sensitization
Protective colloid

• The colloids that help in stabilizing other
colloids are called Protective colloids.
• This protective colloidal property is measured
in GOLD NUMBER.
Ex:
1. Colloidal gold (red) + electrolyte
coagulation (violet)
2. Colloidal gold (red) + Gelatin Colloid
Protective Colloid Stable

• Gold Number is defined as the minimum amount
of protective colloid in milligrams which prevents a
colour change from red to violet of 10ml gold sol by
the addition of 1 ml of 10%NaCl solution.
• Coagulation of gold sol is indicated by colour change
from red to blue/purple when particle size increases.
• More is the gold number, less is the protective
power of the lyophilic colloid.
Protective colloid Gold Number
Gelatin 0.005-0.01
Haemoglobin 0.03-0.07
Sodium Oleate 1-5
Dextrin 6-20

THANKYOU

Pharmaceutical Colloidal Dispersion

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