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DISPERSED SYSTEMS
A disperse system may be defined as a system in which one substance (the dispersed
phase) is dispersed as particles throughout another (the dispersion medium or
continuous phase). We can classify these systems on the basis of the physical shape
and size of the dispersed particles. Matter exists as gas, solid or liquid, so many
different types of dispersed systems are possible.
The dispersed material may range in size from particles of atomic and molecular
dimensions to particles where the size is measures in millimetres. Because of this wide
range, we can classify disperse systems on the basis of the mean particle diameter of
the dispersed material. NB. Size limits are somewhat arbitrary as there is no
distinct transition between the 3 systems.
COLLOIDS
TYPES OF COLLOIDAL SYSTEMS
Lyophilic Colloids
In these systems, there is affinity between the colloidal particles and the dispersion
medium (solvent-loving). Owing to their affinity for the dispersion medium, such
materials form colloidal dispersions or sols with relative ease. To obtain these colloids,
we merely dissolve the material in the solvent being used e.g. gelatin in water. The
affinity of the particles for the solvent renders these systems thermodynamically stable.
Solvation occurs in these colloids - the attachment of solvent molecules to molecules
of the dispersed phase. In the case of hydrophilic colloids in which water is the
dispersion medium, this is termed hydration.
Dispersed phase - organic molecules e.g. gelatin, acacia, insulin, albumin, rubber and
polystyrene. The first 4 form hydrophilic colloids i.e. the dispersion medium is water.
The last 2 are dissolved in nonaqueous, organic solvents - lipophilic colloids. Note that
a material that forms a lyophilic colloid in one liquid such as water, may not do so in
another liquid such as benzene. So BOTH phases are important.
Lyophobic colloids
The dispersed phase has little, if any, attraction for the dispersion medium. These are
lyophobic (solvent-hating) and their properties differ from those of lyophilic colloids. The
main reason is the absence of a solvent sheath around the particles.
The dispersed phase of these colloids is generally composed of inorganic particles
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dispersed in water e.g. gold, silver, sulphur. Because there is no affinity for the solvent,
spontaneous coalescence occurs which indicates that these systems are unstable and
that attractive forces exist between the particles.
As these do not form spontaneously, it is necessary to employ special methods to
prepare these colloids. Either dispersion or condensation methods are used:
Dispersion methods
► Coarse particles are reduced in size by the use of high-intensity ultrasonic
generators operating at frequencies in excess of 20 000 cycles per second.
► A second dispersion method involves the production of an electric arc within a
liquid. Owing to the intense heat generated by the arc, some of the metal of the
electrodes is dispersed as vapour, which condenses to form colloidal particles.
Condensation methods
► These involve a high degree of initial supersaturation followed by the formation
and growth of nuclei. Supersaturation may be brought about by a change in
solvent or a reduction in temperature.
► Chemical reaction such as reduction, oxidation or hydrolysis..
3. Association colloids
We have already dealt with this class. These association or amphiphilic colloids consist
of surface-active agents which aggregate into micelles. Below the CMC, they exist as
monomers, at and above the CMC, aggregates form (micelles) which may contain 50 or
more monomers The size of these micelles lies in the colloidal size range. Formation is
spontaneous, provided that the concentration of the SAA in solution exceeds the CMC.
SIZE AND SHAPE OF COLLOIDAL PARTICLES
Particles lying within the colloidal size range possess a surface area that is enormous
compared with the surface area of an equal volume of larger particles. This results in
many of the unique properties of colloidal dispersions.
The shape adopted by colloidal particles is important, since the more extended the
particle, the greater its specific surface and the greater the opportunity for attractive
forces to develop between the particles of the dispersed phase and the dispersion
medium.
OVERHEAD Examples of shapes that may be assumed. Physical Pharmacy
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OPTICAL PROPERTIES OF COLLOIDS
When a strong beam of light is passed through a colloidal sol, a visible cone is formed.
This results from the scattering of light by the colloidal particles. This is the FaradayTyndall Effect. The ultramicroscope allows us to examine the points of light
responsible for the Tyndall cone. An intense light beam is passed through the sol
against a dark background at right angles to the place of observation. Although the
particles cannot be directly seen, bright spots corresponding to the particles can be
observed.
The use of the ultramicroscope has declined in recent years since it often does not
resolve lyophilic colloids. The electron microscope yields pictures of the actual
particles and is now used to observe the size, shape and structure of particles.
The light scattering property is widely used for determining the molecular weight of
colloids.
KINETIC PROPERTIES OF COLLOIDS
These properties relate to the motion of particles with respect to the dispersion medium.
The motion may be thermally induced (Brownian movement, diffusion, osmosis),
gravitationally induced (sedimentation) or applied externally (viscosity). Electrically
induced motion is considered in the section on the electric properties of colloids.
Thermally : Brownian Motion
This results from the bombardment of the colloidal particles by the molecules of the
dispersion medium. The velocity of particles increases with a decrease in particle
size. If the viscosity of the medium is increased, Brownian motion decreases and
finally stops.
Thermally : Diffusion
Particles diffuse spontaneously from a region of higher concentration to one of lower
concentration, until the concentration is uniform. Diffusion is a direct result of
Brownian motion.
Thermally : Osmotic Pressure
The particles in a colloid may consist of aggregates of several molecules, but each
aggregate acts as a single unit for colligative purposes. Thus the osmotic pressure
exerted by such a colloidal system will be small.
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Gravitationally : Sedimentation
The sedimentation of spherical particles may be expressed using Stokes' Law (see
suspensions). If particles are subjected only to the force of gravity, then the lower
limit of particles obeying Stokes' equation is about 0.5 μm. This is because Brownian
movement becomes significant and tends to offset sedimentation and promote
mixing. So with increasing particle size, Brownian motion decreases, while the
tendency to sediment increases.
Applied externally : Viscosity
Viscosity is an expression of the resistance to flow of a system under an applied
stress. The more viscous a liquid, the greater the applied force required to make it
flow at a particular rate.
Comparing the viscosity of the lyophobic and lyophilic colloids:
The viscosity of colloids is affected by the shapes of particles of the disperse phase.
Spheric particles form dispersions of relatively low viscosity, while systems containing
linear particles are more viscous.
Lyophobic: Viscosity is not much greater than that of the liquid vehicle. This is so even
for comparatively high fractions of the dispersed phase. Particles here are symmetric
and unsolvated.
Lyophilic: In contrast, the apparent viscosity of lyophilic colloids is much greater than
the viscosity of the vehicle, even at low concentrations of the dispersed phase. Particles
here are highly asymmetric and solvated.
ELECTRIC PROPERTIES AND STABILITY OF COLLOIDS
These are the properties that depend on, or are affected by, the presence of a charge
on the surface of a particle. The presence and magnitude, or absence of a charge on a
colloidal particle is an important factor in the stability of colloidal systems.
Stabilization is achieved essentially by 2 means:
► dispersed particles can be provided with an electric charge
► each particle is surrounded with a protective solvent sheath that prevents mutual
adherence when the particles collide (only significant in lyophilic systems).
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Stabilisation of lyophobic colloids
Lyophobic colloids are thermodynamically unstable and the particles are stabilised only
by the presence of electric charges on their surface. These charges originate from
preferential adsorption of specific ions from solution. The like-charge produces a
repulsion that prevents coagulation of the particles. Four researchers, Verwey,
Overbeek, Derjaguin and Landau developed a theory called the DLVO theory that
describes the stability of lyophobic colloids. To understand it, we must first consider the
attractive and repulsive forces that operate between approaching particles, then to
examine the combined effect of these opposing forces.
OVERHEAD : Net potential energy of interaction graph
Repulsive forces
The absorbed charges influence the distribution of positive and negative ions in the
layers of solution that surround each particle. This distribution is also influenced by
thermal motions in the solution, therefore each particle is surrounded by an EDL
similar to the distribution we saw previously.
When 2 particles approach each other, the atmospheres of counterions or diffuse
parts of the EDL overlap. A redistribution of charge occurs in each layer and
there is work involved in distorting the diffuse layers. Therefore a net repulsive
energy is obtained so a repulsive force will be exerted between the 2 particles. To
overcome this repulsion, work or energy is needed to bring the particles closer
together.
Attractive forces
Even when particles aggregate, repulsive forces are exerted, therefore for
aggregation to occur, an attractive force must be equal to or greater in its magnitude
and range of operation to the repulsive force. Attraction is provided by van der
Waal's forces which are additive, so the total attraction between 2 particles will be
equal to the sum of all the attractive forces between every atom of one particle and
all those of the other. The additive effect increases the range over which this force is
exerted.
Net potential energy of interaction
The net potential energy of interaction is obtained by adding the repulsive and
attractive potentials at each distance of separation. As the particles approach each
other and a repulsive force is exerted, they either then move apart, or, if there is
enough kinetic energy to overcome repulsion, they will move closer together.
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As particles continue to approach, repulsion between surface charges increases the
net potential energy of interaction (NPEI) to its maximum value (energy barrier). If
the height of this barrier exceeds the kinetic energy of the approaching particles, they
will not come any closer, but will move away from each other.
However, if their kinetic energy exceeds the energy barrier, the particles continue to
approach each other, after which van der Waal's forces become increasingly
important compared to electrostatic repulsion.
The net potential energy decreases to zero, then becomes negative, pulling
particles still closer. The interacting particles will reach the energy depth of the
primary minimum and irreversible aggregation i.e. coagulation will occur. It is unlikely
that enough kinetic energy can be supplied to the particles to enable them to climb
out of the potential energy well, so they are permanently attached to one another.
Main determinant of stability:
► The height of the primary energy barrier depends on the density of charge on the
surface which is expressed by the surface and zeta potentials, and the resultant
magnitude of electrical repulsion. It is also influenced by electrolyte concentration.
► Addition of electrolyte compresses the EDL and reduces the zeta potential. This
has the effect of lowering the primary maximum energy barrier and as the
concentration of electrolyte increases, the barrier continues to decrease and finally
disappears - at this point rapid coalescence occurs.
OVERHEAD : Influence of electrolyte concentration on height of energy barrier
► The valence of the ions having a charge opposite to that of the particles appears
to determine the effectiveness of the electrolyte in coagulating the colloid. The
precipitating power increases rapidly with the valence of the ion. This is known as the
Schulze-Hardy rule.
e.g. we have a negatively charged colloid and we are going to add both aluminium
chloride and barium chloride. Which one would require the larger concentration to
result in coagulation of the colloid?
Answer: barium chloride since barium is divalent, aluminium is trivalent.
► The energy barrier may also be lowered by adding substances such as ionic surfaceactive agents which are specifically adsorbed within the Stern layer. The Stern and
zeta potentials are reduced whereas the double layer is not compressed.
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Stabilisation of lyophilic colloids
Lyophilic colloids are stabilised by a combination of EDL interaction and solvation.
Both of these stabilizing factors must be sufficiently weakened before attraction
predominates and the colloidal particles coagulate
Hydrophilic colloids are unaffected by the small amounts of added electrolyte which
cause hydrophobic colloids to coagulate; however when the concentration of electrolyte
is high, particularly with an electrolyte whose ions become strongly hydrated, the
colloidal material loses its water of solvation to these ions and coagulates i.e. a "salting
out" effect occurs.
Coacervation: when oppositely charged hydrophilic colloids are mixed, the
particles may separate from the dispersion to form a layer rich in the colloidal
aggregates which is known as a coacervate and is a process of complex
coacervation.
SENSITIZATION AND PROTECTIVE COLLOIDAL ACTION
► The addition of a small amount of hydrophilic or hydrophobic colloid to a
hydrophobic colloid of opposite charge tends to sensitize or even coagulate the
particles i.e. it becomes more susceptible to precipitation by electrolytes. This is
thought by some to be due to reduction of the zeta potential below the critical value.
Others think it is due to a reduction in the thickness of the ionic layer surrounding the
particles and a decrease in repulsion between the particles.
► The addition of large amounts of the hydrophile stabilizes the system as the
hydrophile is adsorbed on the hydrophobic particles which then acquire hydrophilic
properties. This phenomenon is known as protection and the added hydrophilic sol
is known as a protective colloid.
► The protective property is expressed most frequently in terms of the gold number.
The gold number is the minimum weight in milligrams of the protective colloid (dry
weight of the dispersed phase) required to prevent a colour change from red to violet
in 10 ml of a gold sol on the addition of 1 ml of a 10% solution of sodium chloride.
Examples of some gold numbers of protective colloids: gelatin (0.005 - 0.01),
albumin (0.1), acacia (0.1-0.2), sodium oleate (1-5) and tragacanth (2).
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PHARMACEUTICAL APPLICATION OF COLLOIDS
Even though it may not be apparent from the name of a specific drug product, in many
instances one or more of the ingredients of a drug product may be considered a
colloidal dispersion. A number of pharmaceutical compounds will become colloidal
dispersions when added to water e.g. certain inorganic salts, all proteins, surface active
agents and gums.
Mucilages
These are viscous, aqueous systems containing gums, either dissolved or suspended
e.g. acacia mucilage and tragacanth mucilage.
Gels
These are colloidal systems, as will be seen in the section on gels.
Collodions
Collodions are liquid preparations containing pyroxylin in a mixture of ether and
alcohol. Collodions leave a flexible, protective layer over the site of application after
being painted on the skin and allowed to dry. They may provide a means of maintaining
contact of a drug with the skin for a prolonged period and are also used to seal minor
cuts and wounds. The most commonly used preparation is one for removing warts and
corns and contains salicylic acid and lactic acid in collodion (keratolytic agent).
Ionic versus colloidal
► Silver salts are used externally as germicides/antimicrobials. Ionic silver salts cause
a lot of irritation. Colloidal silver chloride, and silver iodide have the same efficacy
(plus more) but do not cause irritation.
► Colloidal iron is less astringent than crystalloidal iron.
► Coarsely powdered sulphur is poorly absorbed when administered orally we say
that it has poor bioavailability. The same dose in a colloidal solution may be absorbed
so completely that it causes a toxic reaction i.e. bioavailability is much higher.
Natural and synthetic polymers
Polymers are macromolecules formed by polymerization or condensation of smaller,
noncolloidal molecules. Natural polymers - proteins are important natural colloids and
are found in the body as components of muscle, bone and skin e.g. collagen, albumin.
Synthetic polymers – are widely used in a variety of drug delivery systems. (see under
Formulation)
Blood plasma substitutes (see pamphlet on Rheomacrodex®)
“Effective colloids retain water in the vascular space and thereby improve
haemodynamics”
These are colloidal dispersions with a particle size such that they are retained in the
blood vessels for an adequate time e.g. natural polymers such as 10% dextran 40 and
hydroxyethyl starch are macromolecules also used as plasma substitutes.
Dialysis
Because of their size, colloidal particles can be separated from molecular particles with
relative ease using the separation technique of dialysis.
► A semipermeable membrane of collodion or cellophane is used, the pore size of
which will prevent the passage of colloidal particles but will permit small molecules
and ions such as urea,, glucose and sodium chloride to pass through.
► Dialysis occurs in vivo. 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 small,
molecular impurities from the body by passage through a semipermeable membrane.
(Polymers in )…Formulation
► The protective ability of hydrophilic colloids is used to prevent the coagulation of
hydrophobic particles in the presence of electrolytes.
► Hydrophilic colloids are used in suspensions as suspending agents to retard
sedimentation as they increase the viscosity of the medium.
► Polymers are extensively used in drug delivery systems to either protect the drug or
modify its release characteristics
e.g. tablet coatings such as the cellulose derivatives which are natural polymers
from vegetable sources e.g. hydroxypropyl methylcellulose, methylcellulose
applied to solid dosage forms to protect drugs from a variety of factors e.g.
atmospheric moisture or degradation under the acid conditions of the stomach.
e.g. drugs contained in polymer matrices to control release rates e.g. Eudragit® consisting of the polyacrylates which are synthetic but biodegradable