COLLOIDAL STATE AND DISPERSE SYSTEMS

SPECIFIC OBJECTIVES

1. Define a colloidal state (size of particles)

2. Describe and classify various disperse systems (Lyophilic, Lyophobic, Association)

3. Outline the properties of colloids (Kinetic, electrical, optical)

4. Outline the methods of preparation of colloids (Dispersion, condensation, Precipitation,

Chemical reaction)

5. Describe Factors influencing stability of colloidal systems (Nature of the dispersion medium,
Viscosity, pH, Charge distribution, Electrolytes)

6. Describe the methods of purifying colloids (Dialysis, Ultrafiltration, Electrophoresis)

7. Define a surface-active agent and describe the formation of micelles

8. Explain the pharmaceutical application of colloids and disperse systems (Formulation of

Dosage Forms)

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DISPERSE SYSTEMS

A disperse system is a system in which one substance (the disperse phase/the non –continuous
phase/the internal phase) is dispersed as particles throughout another (the dispersion
medium/continuous phase/the external phase).

These can be classified based on the physical states of the two phases or on the basis of the size
of the dispersed particles.

(a) Classification based on physical states of the two phases

DISPERSION MEDIUM
DISPERSE SOLID LIQUI GAS
PHASE D
SOLID S/S S/L S/G
LIQUI L/S L/L L/G
D
GAS G/S G/L G/G

(b) Classification based on the size of the dispersed particles

DISPERSED PARTICLE NOTES SYSTEM

PARTICLES SIZE
1. Small molecules or ions Usually less than one Usually mixtures of True
nanometer gases (lyophilic) Solution
2. Single large molecules Larger than those All except G/G class Colloidal
(or ions), or aggregates of above, with an upper Dispersions
small molecules (or ions) size limit of about
one micrometer
3. Aggregates of Larger than those in Lower size limit is one Coarse
molecules (or ions) colloidal dispersions micrometer Dispersion

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COLLOIDAL SYSTEMS

These are polyphasic systems where at least one dimension of the disperse phase measures
between 1-10 nanometers on the lower side, and one micrometer on the upper side.

Colloidal systems contain one or more substances that have at least one dimension in the range
1-10 nanometers at the lower end and one micrometer at the upper end dispersed in a suitable
dispersion medium.

The term “Colloidal” designates a state of matter characterized by submicroscopic dimensions

rather than certain substances.

The word “Colloid” is derived from a Greek word for “glue”. This is because they diffuse very
slowly when dissolved or dispersed in water.

Examples

1. Blood

2. Cell membranes

3. Milk

4. Rubber latex

5. Fog (L/G)

6. Beer foam (G/L)

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DISTINGUISH COLLOIDAL DISPERSIONS FROM COARSE DISPERSIONS

PROPERTY COLLOIDAL DISPERSION COARSE DISPERSION

1. VISIBILITY Particles are usually too fine to be Particles are frequently
visible in a light microscope, visible to
often visible in utramicroscope, the naked eye, and always
and always visible in electron visible in the light
microscope microscope
2. FILTRATION Particles pass through an ordinary Do not pass through an
filter paper, but are retained by dialysis or ordinary filter paper (they
ultrafiltration membranes are retained)
3. Undergo little or no sedimentation or Particles sediment under
SEDIMENTATION creaming; Brownian motion is able to the influence of
maintain the dispersed particles in the gravitational pull
dispersion medium
4. TEXTURE Non gritty texture ( smooth texture) Gritty texture
(Rough texture)
5. PARTICLE SIZE 1-10 nanometers to 1 micrometer Above one micrometer

DESCRIBE THE COLLOIDAL STATE

The Colloidal State is the state of matter of the disperse phase and the dispersion medium;
whether they are solid, liquid or gaseous.

This has given one way of classifying them.

DISPERSION MEDIUM (VEHICLE)

DISPERSE SOLID LIQUID GAS
PHASE SOLID S/S S/L (SOLS) S/G (SOLS)
(i) Zinc oxide paste (i) Suspensions SOLID AEROSOLS
(Zinc oxide in (prednisolone eye (i) smoke

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 Petrolatum) drops; Magnesium- (ii) dust
(ii) Tooth paste Aluminium oral (iii) ephedrine aerosol
(dicalcium phosphate suspension) (iv) isoproterenol
& CaCO3 in aqueous (ii) lotion inhalation
Sodium (betamethasone aerosol
carboxymethyl Valerate)
Cellulose) (iii) colloidal gold
(iii) Colloidal gold in in water
in glass
LIQUID L/S L/L (EMULSIONS) L/G
(i) Absorption bases (i) soya bean oil in LIQUID
(aqueous medium in Water for IV feeding AEROSOLS
Hydrophilic (ii) mineral oil in (i) mist
petrolatum) water (ii) Fog
(ii) Emulsion bases (iii) benzyl benzoate (iii) nasal relief sprays
(oil in hydrophilic emulsion (BBE) (iv) povidone-iodine
ointment) (iii) Milk topical spray
(iii) Butter (oil globules less than (Betadine ® spray)
(iv) mineral oil in wax 1 micrometer)
GAS G/S G/L G/G
SOLID FOAMS TRUE FOAMS NO COLLOIDAL
(i) Foamed plastics (i) Carbonated DISPERSION
(ii) Foamed rubber Beverages
(ii) Effervescent
Salts in water

SOL-is when a solid/liquid droplets in the colloidal size range are dispersed in the fluid medium
i.e. S/L, S/G, L/L or L/G. These can be identified by prefixes that designate the dispersion
medium. e.g. hydrosol (in water), alcosol (in alcohol), aerosol (in air).

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Solid particles may form bridged structures that possesses some mechanical strength. These are
called gels, and can be differentiated as hydrogels, alcogels and aerogels respectively.

THEORY OF COLLODIAL SYSTEMS

When very fine particles within the range of true colloids are wetted and introduced into the
dispersion Medium, they may diffuse or become indiffusible and therefore remain as clumps at
the surface or within the medium.

Diffusible particles disperse evenly within the medium and tend to exist transiently as discrete
units. A common feature of these fine particles is their Larger Specific Surface Area (Surface
area to volume ratio) which renders them highly kinetically unstable hence Brownian Motion
predominates.

As a result, such fine particles tend to aggregate so as to reduce the surface area to volume ratio
by forming floccules or Coalescence until a minimum surface area of equilibrium stable state is
attained.

TYPES OF COLLOIDAL SYSTEMS (BY OSTWALD)

-These are based on the affinity or interaction between the disperse phase and the dispersion
medium.

-It refers mostly to solid-in-liquid dispersions

Colloids are generally classified into three types:

(i) Lyophilic colloids

(ii) Lyophobic colloids

(iii) Association colloids

1. LYOPHILIC COLLOIDS (Solvent –Loving)

These are colloids which are ‘solvent-liking’. There is considerable attraction between the
disperse phase and the liquid vehicle hence extensive solvation.

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(a) Hydrophilic colloidal dispersions (water-loving)

-This is when the dispersion medium is water. The dispersed particles are hydrophilic e.g.
Bentonite, starch, gelatin, acacia, povidone.

-The particles may swell, disperse or dissolve spontaneously in water.

(i) True solution: -water + water soluble polymers e.g. acacia, povidone

(ii) Gelled solution:- polymers at high concentration +/- temperature because they have low
solubility e.g. gelatin, starch

-they gel on cooling to give hydrogels

(iii) Particulate dispersions:- this is where solids remain as discrete, though minute particles
e.g. Bentonite

-They give hydrosols

(b) Lipophilic or Oleophilic dispersions (oil –loving)

-they have pronounced affinity for oils e.g. mineral oil, Benzene, vegetable oils (cotton seed,
peanut oil), essential oils (lemon, peppermint oil).

-0leophilic colloidal dispersions are formed by:

(a) Polymers like gum rubber in benzene or polystyrene in benzene

(b) Magnesium-Aluminium stearate in cotton seed oil

(c) Activated charcoal in ALL oils

Characteristics of Lyophilic colloids

(1) They form spontaneously when the liquid vehicle is brought into contact with the solid phase
(due to the high affinity between phases)

(2) They are thermodynamically stable

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(3) They are reversible (easily reconstituted even after the dispersion medium has been removed
from the solid phase)

(2) LYOPHOBIC COLLOIDS (Solvent-Hating)

-There is little attraction between the disperse phase and the dispersion medium.

(a) Hydrophobic colloids (water -hating)

-particles are not hydrated

-water molecules interact with or attract one another in preference to solvating the particles

e.g. aqueous dispersions of:

(i) Oleophilic material: results in emulsions

(ii) Sulphur, Silver or Gold

(b) Lipophobic colloids (Lipid-hating)

e.g. Water- in- Oil Emulsions

- lyophobic dispersions in Lipophilic vehicles

Characteristics of Lyophobic colloids

(1) Dispersion process does not take place spontaneously

(2) Dispersions are intrinsically unstable

(3) They are irreversible on separation because there is lack of attraction between the disperse
and continuous phases i.e. once the dispersion medium has been separated from the disperse
phase the dispersion is not easily reconstituted.

3. ASSOCIATION COLLOIDS (Colloidal Micelles)

They are micelles in the colloidal size range.

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They are formed when organic compounds with large hydrophobic groups together with strongly
hydrophilic groups in the same molecule ( also called Amphiphilic or Amphipathic molecule)
tend to associate in aqueous or oil solutions into micelles.

The micelles are large enough to qualify as colloidal particles.

Micelle formation occurs at the Critical Micelle Concentration (CMC).

Drawings to Illustrate

(1) Amphiphilic/Amphipathic molecules or ions

(2) Spherical micelle

(3) Reverse micelle

Ionic and non-ionic surfactants exhibit this behaviour. At CMC, physical properties of the
solution show marked changes in osmotic pressure, density, UV spectrum, IR spectrum,
refractive index, diffusion rate and viscosity.

USES of Association Colloids ( Micellar Solubilization)

Micellar Solubilization is where compounds that are poorly soluble in water but soluble in oils
can be dissolved inside the micelles hence brought homogeneously into an overall aqueous
environment.

e.g. –charcoal in water

-coal tar in water

- chalk in water

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PREPARATION OF COLLOIDAL SYSTEMS (METHODS)

1. Dispersion method

2. Condensation method

3. Precipitation method

4. Chemical reaction

Lyophilic Colloids

SIMPLE METHOD OF DISPERSION is used

The affinity of Lyophilic colloids for the dispersion Medium leads to a spontaneous formation of
colloidal dispersion E.g. Acacia, tragacanth, Methyl Cellulose and certain other cellulose
derivatives readily disperse in water, when the material is placed in contact with water

E.g (i) acacia is readily dispersed in water

(ii) gelatin disperses easily in hot water

Lyphobic Colloids

Special methods of dispersion are used. This is because the dispersion is not spontaneous; it
needs special treatment.

Preparation of Lyophobic colloids can be done in any of the three ways:

(a) DISPERSION METHOD

This involves the breakdown of large particles into very fine particles of colloidal
dimensions (i.e Less than 1 μm). The reduction in size is done using Colloid Mills and
Wave-driven Ultra-Sonics.

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(i) Colloid mills /micronizers/homogenizers: mechanical dispersion method

The mills cause the dispersion of coarse material by shearing in a narrow gap between a
static cone and a rapidly rotating cone

(ii) Electrical dispersion (Bredig’s method)

It happens when certain metals are dispersed by the passage of an electric arc between
electrodes made of the metal and immersed in the dispersion medium.

(iii) Ultrasonic irradiation (sounds higher than what humans can hear!)

This involves the passage of ultrasonic waves through a dispersion medium to produce
alternating regions of cavitation and compression in the medium. The cavities collapse
with great force and cause the breakdown of coarse particles dispersed in the liquid.

(iv) Peptisation

This is where finely divided solid particles are converted into a colloidal dispersion by
the addition of specific ions that preferentially adsorb at the surface stabilizing the
dispersion.

Procedure

Aggregates or secondary particles are broken down into smaller aggregates or into
primary particles respectively in the colloidal size range.

NB: Peptisation is synonymous with deflocculation. Flocculation is the formation of

aggregates (floccules). Peptising agents are usually surfactants, water soluble polymers or
ions which are adsorbed at the particle surface

Example:

Activated charcoal powder in water forms a grey, transluscent suspension (aggregates)

When 0.1% sodium lauryl sulphate (surfactant) is added to the suspension, a finely
dispersed particles with a deep black and opaque dispersion is obtained.

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(b) CONDENSATION METHOD

This involves aggregating of extremely smaller particles such as Molecules into particles
of Colloidal dimensions. This is done by rapid production of Supersaturated Solution of
colloidal Material under Conditions in which it is deposited in the medium as colloids
and not as a precipitate. Eg Colloidal silver iodide.

(i) Ostwald’s Ripening

This is observed when very small particles dissolve spontaneously into a solution to
deposit onto larger particles hence growth and subsequent separation of solid particles
from a liquid. It involves the rapid production of supersaturated solutions of the colloidal
material under conditions in which it is deposited in the dispersion medium as colloidal
particles and not as a precipitate.

The supersaturated solution is obtained when the solubility of a compound in water is

exceeded, hence precipitate or crystallize. The rate depends on the growth of a nucleus
(nucleation) e.g due to solid impurities.

The nucleus must exceed a critical size before they become stable and capable of growing
into colloidal size crystals.

(ii) Physical reactions that result in colloidal particles (condensation)

(a) alcoholic solution of sulphur and water condenses to give a bluish-white colloidal
dispersion

(b) sulphur vapour with water condenses to a colloidal dispersion (sulphur vapour
condensed on cold solid surface)

(c) sublimed/flowers of sulphur with water, and a surfactant added gives a hydrosol

(d) alcoholic solution of a resin (resinous tincture) added slowly into water gives a
colloidal dispersion of the resin.

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NB: Resin is the sticky substance produced by some trees; used for varnish and medicine.

(c) CHEMICAL REACTION

This is where a chemical reaction results in the formation of the colloidal material. e.g.

(i) Colloidal sulphur

Pass hydrogen sulphide through a solution of sulphur dioxide

2H2S + SO2 ---------- 3S + 2H2O

(ii) Colloidal Arsenious Sulphide

Pass hydrogen sulphide through a solution of arsenic trioxide

AS2O3 + 3H2S ---------- AS2S3 + 3H20

(c) Colloidal Aluminium Hydroxide

Hydrolysis of Aluminium chloride give a colloidal dispersion

AlCl3 + 3H2O boil/Add base ---------- Al(OH)3 + 3HCl

NOTE

After preparation, Molecular Impurities are separated from Colloidal particles in the
dispersion Medium by passing through Cellulose nitrate filter Membrane. This method
of purification of colloidal dispersion is known as dialysis.

Stirring enhances the process of dialysis by;

i) Maintaining a high concentration gradient of diffusible molecules across the

membrane.

ii) Renewing the outer Liquid from time to time.

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DIFFERENCES IN PROPERTIES BETWEEN LYOPHILIC AND LYOPHOBIC
COLLOIDS

Property Lyophilic sol./Colloids Lyophobic colloids

Concentration Consists of a high Consists of Low Concentration of
concentration of Colloidal Particles.
colloidal particles.
Viscosity Highly viscous due to Similar or Less viscous due to Low
high concentration of concentration of Colloidal Particles
colloidal particles.
Preparation/formation of Colloidal particles Colloidal Particles do not disperse
dispersion disperse Spontaneously spontaneously due to high interfacial
upon contact with the surface free energy. i.e are
medium. Hence the thermodynamically unstable till free
interfacial free energy energy is Lowered. Special treatment
is low. Ease of is required.
dispersion of material
in the dispersion
medium
Stability Relatively More stable. Relatively less stable due to high
However, its stability interfacial free energy. However, its
depends the charge and stability depends on the charge on
solvation of particles. particles.
Effect on electrolytes eg Salts Particles are generally Particles are very sensitive to added
stable in the presence of electrolyte hence low concentrations
electrolytes. However, of the same cause them to
they may be ‘Salted aggregate/precipitate.
out’ by high
concentration of soluble

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 electrolytes into
amorphous droplets
known as Coacervates.
Association: reversibility after Particles exist as - Particles tend to aggregate
precipitation ( reforms when discrete Units. irreversibly.
precipitated material is added However, the
to fresh dispersion medium) aggregates that may
form are often Loose
and hence reversible.
Solvation Particles are Solvated Particles are Unsolvated and are
and are usually usually Symmetrical
asymmetric
Stability towards prolonged Stable Unstable because ions necessary for
dialysis stability are removed by dialysis
Tyndall Effect Weak; particles are not Strong; particles are readily detected
easily detected by ultra by utramicroscope
microscope
Protective ability Capable of acting as Incapable of acting as protective
(susceptibility to precipitation protective colloids colloids and often require additives
by electrolytes) such as material for stability

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 STABILITY OF COLLOIDAL SYSTEMS

Colloidal dispersions are more stable than coarse dispersions. This is because the larger particles
in the coarse dispersion settle more rapidly under the influence of gravity hence sedimentation.

Factors that determine the rate of sedimentation are explained by STROKE’S LAW. The law is
derived from dilute suspensions of rigid uniform spheres, settling at a velocity which produces
no turbulence in the fluid medium i.e. free settling.

MODE OF ACTION OF STABILIZING FACTORS (STABILIZERS)

1. Ionogenic groups at the particle surface.

-these groups ionize to give electric charges e.g carboxyl to carboxylate ions. It happens in
hydrophilic colloids as Charge distribution.

2. Peptising ions

-these are specific ions from the solution that preferentially adsorb onto the colloidal particles
hence the particles get surrounded by an electric double layer. It happens in hydrophobic colloids
as Charge distribution.

3. Non-ionic surface active agents (macromolecules)

-these adsorb at the particle surface and therefore stabilize aqueous preparations due to the
Nature of dispersion medium (water).

FORCES AFFECTING STABILITY OF COLLOIDS

1. Repulsive Forces

They manifest when particles approach each other, and the diffuse parts of their electrical double
layers overlap. This leads to a distribution of the charge in each layer and repulsion will be
exerted between the particles. This implies that Repulsive potential is predominantly at greater
distances.

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2. Attractive forces

These are weak, but additive forces between atoms. These are comparable in magnitude and
range of operation to the repulsive forces. Repulsive forces help overcome aggregation process.
This implies that the attractive potential predominates as the distance between the particles
decreases.

Conclusion: Coalescence will occur only if the approaching particles possess sufficient
activation energy to overcome the predominant repulsive forces and pass into the region where
the attractive forces predominate.

The height of the energy barrier (repulsive forces) will determine the effectiveness in preventing
the aggregation of the dispersed particles. If you reduce the barrier, you reduce the stability of
the dispersion.

FACTORS AFFECTING THE STABILITY OF COLLOIDAL DISPERSIONS

1. Nature of the Dispersion medium; Aggregation, Agglutination and flocculation

Consider water as a dispersion medium :

-Hydrosols (SOLID/WATER) of hydrophobic substances are intrinsically unstable hence

spontaneously coalescence.

-Hydrosols of hydrophilic substances are stable. Hydrophilic materials form colloidal dispersions
spontaneously on addition to water

Inference: hydrosols of hydrophobic substances must be stabilized using stabilizing factors to

prevent reaggregation i.e coagulation and flocculation.

2. Viscosity : Sedimentation

Consider Stroke’s Law:

-The rate of sedimentation is inversely proportional to viscosity.

This means that the more viscous the dispersion the less the sedimentation.

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Dilute solutions easily separate into a solvent phase practically free of the solute; and a viscous
liquid phase of practically all the solute.

Concentrated solution forms a continuous network of precipitating chains attached to one another
through weak cross-links. These are more stable and undergo limited sedimentation.

3. Temperature: Fluctuations of storage temperature

Most water-soluble polymers have higher solubilities in hot than in cold water and tend to
precipitate on cooling. This is because the sheaths of hydration surrounding adjacent chains
become too sparse to prevent interchain attraction.

Gels liquefy when heated above gelation temperature. Gelation is rarely observed above 34oC
regardless of the concentration. This implies that gelatin solutions do not gel at body
temperature; and therefore gelatin dissolves readily in water at body temperature.

4. pH : Change in pH

-At acidic pH (e.g gastric pH), carboxyl groups are not ionized because they are weakly acidic.
The interchain ionic bonds are practically non-existent. This leaves the weak Van Der Waals
forces to act. Amino groups are ionized hence active.

-At alkaline pH (e.g duodenal pH), the amino groups (alkyl ammonium, guanidinium,
imidazolium) are not ionized and hence their interchain ionic bonds are absent. The carboxyl
groups are ionized and hence ionic bonds are present.

-At Isoelectric pH, both carboxyl and amino groups are ionized. The attachment between
adjacent chains due to attraction between negative and positive groups is most extensive.

5. Charge Distribution

Dispersions with one kind of particle charged (i.e. positively charged only or negatively
charged only), electrostatic repulsion tends to prevent the particles from approaching closely
enough to come within effective range of each other’s Van der Waals attractive forces. This will
stabilize the dispersion against interparticle attachments or coagulation.

For oppositely charged particles, they will attract and coagulate. Such systems are less stable.

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6. Effects of Electrolytes: Polymer and electrolyte Concentration.

(i) Concentration of electrolytes

An increase in concentration of ions in the dispersion medium has the effect of compressing the
diffuse part of the electrical double layer hence decreasing it. This also decreases repulsive
potential.

Explanation: the energy barrier that opposes aggregation decreases, as the concentration of
added electrolytes increases and finally disappears. When the barrier ceases to exist, rapid
coalescence of the particles occurs and large aggregates become visible in the system.

(ii) Valency of the ion of opposite charge to the colloidal particle (Schulze-Hardy Rule)

Consider the trivalent Aluminium chloride (AlCl3) and divalent Barium Chloride (BaCl2): lesser
concentration of AlCl3 than BaCl2 will be used to coagulate rapidly a negatively charged colloid.

Schulze-Hardy Rule states that the Flocculation value of the electrolyte is inversely proportional
to the valency of ion of opposite charge raised to power 6.

Pharmaceutical use of this property

(i) To assess original stability of colloidal dispersion

The greater the concentration of the electrolyte required to produce rapid coagulation, the greater
the stability of the original system.

Mode of action of the above: “SALTING OUT” in hydrophilic colloids: strongly hydrated
inorganic salts e.g. Ammonium sulphate, Aluminium Chloride, and Barium Chloride, bind part
of the water of the colloid solution in order to become hydrated. Competition for water of
hydration dehydrates the colloidal particles and precipitates them.

Hydrophilic colloids are stabilized by the affinity that exists, between the colloidal particles and
the dispersion medium (water). They can only be precipitated by the following, in a process
called “salting out”

(a) very soluble electrolytes

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 (b) very high concentration of electrolytes

(c) electrolytes that are strongly hydrated

(ii) Fractional Precipitation

This is a process whereby the components of a mixture of hydrophilic colloids can be separated.
Fractional precipitation is achieved by “salting out” of the various components at different
concentration of the electrolyte.

(iii) Can help differentiate hydrophilic from hydrophobic colloids

Hydrophilic colloids are much more stable to the presence of added electrolytes than
hydrophobic colloids. The reason behind this is the compression of the diffuse part of the
electrical double layer in the presence of additional counter-ions. This is faster in hydrophobic
colloids because of the fewer ions/less water of hydration.

EFFECTS OF MIXING DIFFERENT COLLOIDS

1. Mutual Precipitation ( in Charged hydrophobic colloids)

This may occur when two hydrophobic colloids with oppositely charged particles are
mixed. This is due to attractive forces exerted between the particles.

2. Coacervate Formation ( in charged hydrophilic colloids)

This may occur when oppositely charged hydrophilic colloids are mixed hence a layer rich
in colloidal material separates. The layer is the coacervate.

3. Sensitisation (hydrophobic colloid and very small amounts hydrophilic colloid)

In the presence of very small amounts of hydrophilic colloid, a hydrophobic colloid may
become more susceptible to precipitation by electrolytes. It is thought to arise from the
adsorption of various parts of each chain-like hydrophilic colloid onto several hydrophobic
particles.

(iv) Protection (hydrophobic colloids and larger amounts of hydrophilic colloids)

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This is the increase in stability of hydrophobic colloids towards the precipitating effects of
electrolytes by the presence of hydrophilic colloids in concentration several times those required
for sensitization.

NB: the hydrophilic colloids are protective. Protection arises from their adsorption over the
entire surface of each hydrophobic particle, so that the latter acquires some hydrophilic
properties and is therefore able to withstand the effects of electrolytes.

METHODS OF PURIFICATION OF COLLOIDS

1. Dialysis
2. Ultrafiltration
3. Electrophoresis/Electrodialysis

(1) Dialysis

The Colloidal dispersion is placed inside a cellophane sac dipping in water. Cellophane is made
of sheets or tubes of cellulose giving a pore structure (membrane).

The small solute Molecule diffuse out of the sac into the water while the

Colloidal Material is retained inside because of its size.

The rate of dialysis can be enhanced by:

(i) increasing the surface area of the Membrane

(ii) stirring

(iii) replenishing the filtrate

(iv) maintaining a high concentration gradient across the membrane by applying pressure or
electric potential

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Pharmaceutical use of Dialysis

 Used to purify sols (Colloidal solutions) in the lab. because of the difference in
diffusibility that can be used to separate micromolecular impurities
 Used to study the binding of drugs by proteins in plasma (protein binding) ie plasma is
analogous to Colloidal solution
NB: A colloidal dispersion may become diluted during dialysis because water will pass through
the membrane under the influence of the osmotic pressure of the colloid. Such dilution may be
prevented by applying to the colloid a pressure that is equal to or greater than its osmotic
pressure (dialysis under pressure)

(2) Ultra filtration

The Colloidal solution is placed in a compartment that is enclosed by dialysis Membrane and
pressure is applied. Pressure is applied because the pores in the membrane are so small hence the
rate of flow of the liquid dispersion medium through the membrane is slow.
When pressure is applied (utrafiltration), the liquid medium and small solute molecules are
forcefully filtered through the membrane, while the colloidal particles are retained.
-Nitrocellulose filter Medium is the most commonly used

NB:
 In sieving mechanism, all components smaller than the pore size of the filter membrane
pass through it.
 The pressure is either positive (provided by gas pressure) or negative ( provided by
suction on the filtrate side)
 Avoid increase in concentration of sol on the sol side and remove dissolved impurities
completely by replenishing ultrafiltrate with equal volume of water and stir
 It is possible to manufacture membranes of different degrees of porosity. The use of a
series of ultrafilters with gradually decreasing pore sizes allows for the particle size of a
colloid to be determined
 Constant removal of the ultra-filtrate and strirring the slurry (sol) enhance the rate of
filtration and will completely remove the impurities.

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(3) Electrophoresis

An electrical potential is used to increase the rate of movement of ionic impurities through a
dialyzing membrane and so provide a more rapid purification.

-The law molecular weight impurities removed in this process must be electrolytes (charged:
anions to anode while cations to cathode)
The anions migrates from the sol into the anode compartment, whereas the cations migrate into
the cathode compartment.
The Mechanism is that, charged colloidal particles tend to migrate towards the electrode of
opposite charge.
The electrical potential should not affect the stability of the colloid.
NB: Haemodialysis involves purification of blood in uremic patients. It acts like an artificial
kidney to remove urea, creatinine, uric acid, phosphate, other metabolites, excess sodium
chloride, potassium chloride etc. The dialyzing fluid contains sodium, potassium, calcium,
chloride and acetate ions, dextrose etc in the same concentration as normal plasma.
The dialyzing fluid contains no urea, creatinine, uric acid, phosphates and other metabolites
excreted by the kidney, hence these diffuse from patient’s blood into the fluid until their
concentration is the same in blood and fluid.

(4) Others:

(i) Salting Out

This is also known as ionic precipitation. It involves the addition of Na+.

Na+ binds to anionic impurities and solubilize them.

The anions (Impurities) in solution can then be Ultrafiltrated.

(ii) Ion exchange chromatography

This involves passage of sol through an ionically charged membrane.

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They repel similarly charged particles. The repelled charges are filtered into the filtrate while
those attracted are retained.

PROPERTIES OF COLLOIDAL SYSTEMS

1. Electrical properties

2. Optical properties

3. Kinetic properties (i. Brownian motion ii. Osmotic iii. Diffusion iv. Gravitational)

4. Particle size specificity

1. ELECTRICAL PROPERTIES

When an electric current is passed through the colloidal dispersion in a suitable cell, particles
migrate towards one of the electrodes, in a process called electrophoresis. Charges are involved
in this process.

Application:

(i) purification of a colloid with ionic impurities

(ii) separation of charged colloidal particles

Sources of electrical properties:

(i) Proteins of Blood Plasma (are amphoteric: poses both positive and negative charges)

- the polypeptide chain end may have surface groups that ionize in various pH ranges

(a) Carboxylic acid groups are ionized into carboxylate ions in neutral to alkaline media. This
confers a negative (anionic) charge to the protein molecule.

(b) Amino groups or protein molecule.

NB: For electro-neutrality, neutralizing or counter-ions are located in the immediate vicinity. e.g.
in neutral or alkaline media counter ions are Na+, K+, Ca++,Mg++ for the carboxylate groups.

(c) At intermediate pH (4.5 to 7), the carboxylate anions and amino, imidazole etc. cations
neutralize each other exactly. The protein particle or molecule is neutral hence called
Zwitterion. It is electrically neutral, although both groups are ionized.

This is called the isoelectric pH or point. This is the point of minimum solubility.

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(ii) Electrical Double Layer

It occurs when negatively charged particle surface attracts positive ions from the solution and
repels negative ions. This may also result from preferential adsorption of specific ions (peptising
ions) in hydrophobic colloids.

The counter ions tend to stick to the surface forming a compact layer which decreases with
distance from surface throughout a diffuse layer. This gives two layers of oppositely charged
ions.

An electric potential develops (the Zeta potential). This is because work is required to bring a
unit electric charge from the bulk solution to the layer (it must overcome repulsive forces).

(iii) Negatively-charged colloids

They move towards the ANODE (+ve) electrode.

Examples: (a) Hydrated Aluminium silicate (Kaolin)

(b) Hydrated Aluminium Magnesium silicate (Attapulgite)

(c) Sulphur

(iv) Positively-charged colloids

They move towards the CATHODE (-ve) electrode.

2. OPTICAL PROPERTIES

These involve the light scattering properties of the colloids. Light changes in direction due to
change in density of the medium i.e. refractive index.

Uniform refractive index allows light to pass the medium undeflected.

Very small particles in the dispersion appear transparent when viewed from the front when light
is behind.

NB: Particles or droplets with diameter less than the wavelength of visible light are transparent
and clear to the naked eye. The rainbow colours: ROYGBIV range from wavelength of 650nm
(for Red) to 450nm (for Blue); most colloidal particles are therefore smaller than this.

Colloidal particles (about 1micrometer) may scatter part of the light in all direction.

Mechanism of Action

A beam of light striking a particle polarizes its atoms and molecules.

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The induced dipoles (pair of poles that are –ve and +ve) act as secondary sources of light, re-
emitting weak light of the same wavelength as the incident light. This is called light scattering.

The scattered light radiates in all directions away from the particle forming a cone (the Tyndall
Cone)

Applications of Optical property

(i) MICROSCOPY –Dark field microscope; Ultra-microscope; Electron microscope

It permits observation of particles much smaller than the wavelength of light. They make use of
light scattering principle.

The intensity of the scattered light increases with decreasing wavelength of the incident beam.

When viewed against a dark background, at right angles to the incident light, scattered light is
seen as a bluish white colour in white material.

(ii) SPECTROPHOTOMETRY & PHOTOELECTRIC CALORIMETRY

They make use of turbidity measurements. They measure the intensity of light transmitted in
incident direction i.e. the strength of emergent light. The transmitted light is yellow-brown in
colour in white material.

This may help determine average particle size and particle size distribution of colloidal and
coarse dispersions.

3. KINETIC PROPERTIES

These are properties associated with movement. They include Brownian motion, Osmotic
motion, Diffusion motion and Gravitational motion (Segimentation)

Kinetic properties help us investigate the rate at which changes occur in a particular system and
the factors that influence these.

They provide information that:

(i) give an insight into the mechanism of the change involved

(ii) allows prediction of the degree of change that will occur after a given time has elapsed.

APPLICATION:

(i) Decomposition of medicinal products

(ii) Absorption of drug into living organisms

(iii) Distribution of the drugs in organism

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 (iv) Removal of drugs from organism

(a) Brownian Motion

This is the motion of the particles in a colloidal system due to the bombardment of the particles
by the molecules of the dispersion medium. This appears as erratic movements of particles which
can be viewed in ultra-microscope as bright spots against a dark background.

Brownian motion is opposed by Ostwald’s Ripening which is the spontaneous coarsening of

colloidal particles on aging. This gives large crystals which can be removed by filtration.

Mode of action

Very small particles (have higher solubility) deposit onto the larger particles hence growth.

Indication

This property is useful in helping to counteract the effect of sedimentation and hence maintain
the dispersion of particles in the continuous phase.

(b) Osmotic Motion

Osmosis refers to the spontaneous diffusion of solvent from a solution of low solute
concentration (or pure solvent) to a more concentrated one through a semi-permeable membrane.

Osmosis occurs at constant temperature and pressure. Only the solvent can pass across the semi-
permeable membrane. It depends on the proportion of dispersed solute (colloidal) particles
present in the preparation i.e. is a colligative property. Other colligative properties include:
vapour pressure reduction, elevation of boiling point, and depression of freezing point.

Many aggregates of several molecules act as a single unit for colligative purposes; i.e this
process lowers the osmotic pressure.

Osmotic pressure (OP) is the external pressure that must be applied to the solution in order to
prevent it being diluted by the entry of solvent by osmosis.

Application

Osmotic pressure can be used to calculate the molecular weight of the colloidal material, if they
are made of single large molecules.

(c) Diffusion Motion

Diffusion is the spontaneous transfer of a component from a region in the system where it has a
high chemical potential into one where its chemical potential is lower.

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Movement is achieved by solute molecules acquiring sufficient kinetic energy to break away
from any bond that anchor them to one another.

Diffusion will depend on:

(i) concentration of solute molecules

(ii) temperature

(iii) density gradient

(iv) mechanical agitation and vibration

(d) Gravitational motion

This is motion due to gravity. Stroke’s law states that the rate of sedimentation is directly
proportional to the gravitational pull. This is normally constant, but it can be varied using
positive or negative pressures on the system.

NB: Ionization of solute occurs when solute dissociate into ions. This happens when the
dielectric constant of the solvent is high enough to cause sufficient separation of the oppositely
charged ions. Repulsive and attractive forces will keep the particles in motion.

4. PARTICLE SIZE-SPECIFIC PROPERTY

Particles in a colloidal dispersion fall within the approximate range of 1 nanometer to 1

micrometer.

The actual size may be determined by:

(i) ultramicroscopic measurements

(ii) ultrafilration measurements

(iii) ultracentrifugation measurements

SUMMARY OF PROPERTIES OF COLLOIDS

1. They have an average size range of 1 nanometer to 1 micrometer

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2. They are often spherical in shape.

3. Colloidal particles are subject to random Collision with the

molecules of the dispersion medium and of itself so that each particle makes an irregular
and zigzag path. This is known as Brownian movement.

Particles, therefore sediment at a velocity given by STROKE’S LAW

V =2 r 2 ( p 1 − p 2 )g
9u

Where V = velocity of sedimentation

r = radius (average) of the colloidal particles

(p1 – p2) = Density difference between the colloidal

particles and that of the medium.

g = Acceleration due to gravity

u = Viscosity of the medium

4. Their Molecular Weight can be determined by using Colligative properties e.g. increasing
the Osmotic pressure, depression of freezing point and elevation of boiling point.

It is also determined by visualizing under an Electron Microscope and Light scattering of

an Ultra Microscopy.

5. Colloidal Particles have ionizable surface at the interface hence giving them distinct
features at the interface.

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IMPORTANCE OF COLLOIDAL SYSTEMS IN PHARMACY (Formulation of Dosage
Forms)

1. Increases Specific Surface Area

The efficiency of certain substances is increased when in colloidal state:

Examples (a) Kaolin (Hydrated Aluminium Silicate) : it is used in the adsorption of toxins from
the GIT

(b) Colloidal Aluminium Hydroxide : its ability to neutralize excess acidity in the
stomach increases in colloidal state

2. Decreases the Astringent effect of iron

- Colloidal iron: it is less astringent

- Crystalline iron: it has more astringent properties

NB: Astringent means able to cause cells to shrink by precipitating proteins from their surfaces;
this reduces bleeding and hardens as well as protect the skin.

3. Reduces toxicity of Iodine

- Colloidal iodine: less toxic

- Iodine in aqueous solution: more toxic

4. Colloidal Protein Systems can be purified by “salting out” or pH changes

-addition of electrolytes or changes in pH will change the solubility of the colloidal system hence
precipitate the particles.

5. Protection against effect of added electrolytes

-hydrophilic colloids have a protective ability, hence used to prevent the coagulation of
hydrophobic particles in the presence of electrolytes

6. As Suspending Agents

- hydrophilic colloidal dispersions increases the viscosity of the liquid hence retard
sedimentation of particles in pharmaceutical suspensions. E.g Colloidal anhydrous silica

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7. As Blood Plasma Substitutes

- e.g : Colloidal clays: Bentonite, Hectorite, attapulgite (Aluminium Magnesium Silicate)

-they are finely divided solids which are not easily wetted. They therefore accumulate at the oil-
water interface to yield solid interfacial films.

Advantages of colloidal clays

(i) their emulsions are of good stability

(ii) their emulsions are less prone to microbial spoilage

Disadvantages of colloidal clays

-the resultant emulsions are often of coarse texture

9. As Radiocolloids ( Radioactive colloids)

-these contain radioactive isotopes that can be used for diagnostic and therapeutic purposes in
Nuclear Medicine

Mode of Action: they accumulate in tumours, lesions or emboli hence indicate their locations
and size. They are given intravenously in scintillating (minute) imaging.

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