Colloidal Dispersions in Physical Pharmacy

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Dispersed systems 

consist of particulate

matter, known as the 

dispersed phase

,

distributed throughout a 

continuous 

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. Accordingly, a

convenient means of classifying dispersed

systems is on the basis  of the mean particle

diameter of the dispersed material.

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1.

molecular dispersions.

2.

Colloidal dispersions.

3.

coarse dispersions.

1.

Molecular dispersions 

(less than 1 nm)

Particles invisible in electron microscope Pass

through semipermeable membranes and filter

paper, Particles do not settle down on standing

Undergo rapid diffusion E.g. ordinary ions, glucose

2.

Colloidal dispersions

 (1 nm - o.5 um)

Particles not resolved by ordinary microscope, can be

detected by electron microscope. Pass through filter

paper but not pass through semipermeable membrane.

Particles made to settle by centrifugation Diffuse very

slowly E.g. colloidal silver sols, natural and synthetic

polymers, cheese, butter, jelly, paint, milk, shaving

cream.

3- Coarse dispersions

 (> 0.5 um)

Particles are visible under ordinary microscope. Do not

pass through filter paper or semipermeable membrane.

Particles settle down under gravity do not diffuse E.g.

emulsions, suspensions, red blood cells.

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Particles in the colloidal size range possess a

surface area that is enormous compared with the

surface area of an equal volume of larger particles.

Thus, a cube having a 1-cm edge and a volume of 1

cm3 has a total surface area of 6 cm2. If the same

cube is subdivided into smaller cubes each having

an edge of 100 μm, the total volume remains the

same, but the total surface area increases to

600,000 cm2. This represents a 

10

5

-fold increase in

surface area.

specific surface 

is defined as the surface area

per unit weight or volume of material. In the

example just given, the first sample had a specific

surface of 6 cm2/cm3, whereas the second sample

had a specific surface of 600,000 cm2/cm3. The

possession of a large specific surface results in

many of the unique properties of colloidal

dispersions. For example, platinum is effective as a

catalyst only when in the colloidal form as

platinum black. This is because catalysts act by

adsorbing the reactants onto their surface. Hence,

their catalytic activity is related to their specific

surface.

The color of colloidal dispersions is related to the

size of the particles present. Thus, as the particles

in a red gold sol increase in size, the dispersion

takes on a blue color. Antimony and arsenic

trisulfides change from red to yellow as the

particle size is reduced from that of a coarse

powder to that within the colloidal size range.

Because of their size, colloidal particles can be

separated from molecular particles with relative

ease. The technique of separation, known as

dialysis, uses a semipermeable membrane of

collodion or cellophane, the pore size of which will

prevent the passage of colloidal particles, yet

permit small molecules and ions, such as urea,

glucose, and sodium chloride, to pass through. The

principle is illustrated in Figure 16-1,

Fig. 

16-1

.Sketch showing the removal of electrolytes

from colloidal material by diffusion through a

semipermeable membrane. Conditions on the two

sides, A and B, of the membrane are shown at the start

and at equilibrium. The open circles are the colloidal

particles that are too large to pass through the

membrane. The solid dots are the electrolyte particles

that pass through the pores of the membrane

.

at equilibrium, the colloidal material is retained

in compartment A, whereas the subcolloidal

material is distributed equally on both sides of

the membrane. By continually removing the

liquid in compartment B, it is possible to obtain

colloidal material in A that is free from

subcolloidal contaminants. Dialysis can also be

used to obtain subcolloidal material that is free

from colloidal contamination—in this case, one

simply collects the effluent.

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.

The shape of colloidal particles in

dispersion is important:



The more extended the particle the greater

its specific surface the greater the attractive

force between the particles of the dispersed

phase and the dispersion medium.



Flow, sedimentation and osmotic pressure of

the colloidal system affected by the shape of

colloidal particles.



Particle shape may also influence the

pharmacologic action.

Fig. 16-2

.Some shapes that can be assumed by

colloidal particles: (

a

) spheres and globules, (

b

)

short rods and prolate ellipsoids, (

c

) oblate

ellipsoids and flakes, (

d

) long rods and threads, (

e

)

loosely coiled threads, and (

f

) branched threads.

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A. 

on the basis of the interaction of the particles,

molecules, or ions of the dispersed phase with

the molecules of the dispersion medium.

1.Lyophilic Colloids



Systems containing colloidal particles that

interact to an appreciable extent with the

dispersion medium are referred to as lyophilic

(solvent-loving) 

colloids. Owing to their affinity

for the dispersion medium, such materials

form colloidal dispersions, or sols with relative

ease.



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.



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.



In the case of hydrophilic colloids, in which

water is the dispersion medium, this is termed

hydration.



Most lyophilic colloids are organic molecules,

for example, gelatin, acacia, insulin, albumin,

rubber, and polystyrene.



gelatin, acacia, insulin, albumin produce

lyophilic colloids in aqueous dispersion

media (hydrophilic sols). Rubber and

polystyrene form lyophilic colloids in

nonaqueous, organic solvents. These

materials accordingly are referred to as

lipophilic 

colloids.

2. Lyophobic Colloids



The second class of colloids is composed of

materials that have little attraction, if any, for

the dispersion medium. These are the

lyophobic 

(solvent-hating) 

colloids.



Lyophobic colloids are generally composed of

inorganic particles dispersed in water.

Examples of such materials are gold, silver,

sulfur, arsenous sulfide, and silver iodide.



In contrast to lyophilic colloids, it is necessary

to use special methods to prepare lyophobic

colloids. These are 

(a) dispersion methods, 

in

which coarse particles are reduced in size,

Dispersion can be achieved 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 vapor,

which condenses to form colloidal particles.

Milling and grinding processes can be used,

although their efficiency is low. So-called colloid

mills, in which the material is sheared between

two rapidly rotating plates set close together,

reduce only a small amount of the total particles

to the colloidal size range.

(b) condensation methods

, in which materials of

subcolloidal dimensions are caused to aggregate

into particles within the colloidal size range. The

required conditions for the formation of lyophobic

colloids by condensation or aggregation involve a

high degree of initial supersaturation followed by

the formation and growth of nuclei.

Supersaturation can be brought about by change

in solvent or reduction in temperature. For

example, if sulfur is dissolved in alcohol and the

concentrated solution is then poured into an

excess of water, many small nuclei form in the

supersaturated solution. These grow rapidly to

form a colloidal sol.

Other condensation methods depend on a

chemical reaction, such as reduction, oxidation,

hydrolysis, and double decomposition. Thus,

neutral or slightly alkaline solutions of the

noble metal salts, when treated with a

reducing agent such as formaldehyde or

pyrogallol, form atoms that combine to form

charged aggregates.

3. Association Colloids

Association or amphiphilic colloids form the

third group in this classification. As shown in

the Interfacial Phenomena chapter, certain

molecules or ions, termed amphiphiles or

surface-active agents, are characterized by

having two distinct regions of opposing

solution affinities within the same molecule or

ion. When present in a liquid medium at low

concentrations, the amphiphiles exist

separately and are of such a size as to be

subcolloidal. As the concentration is increased,

aggregation occurs over a narrow

concentration range. These aggregates, which

may contain 50 or more monomers, are called

micelles.

Because the diameter of each micelle is of the

order of 50 Å, micelles lie within the size range

we have designated as colloidal. The

concentration of monomer at which micelles

form is termed the 

critical micelle

concentration

(

CMC

). The number of monomers

that aggregate to form a micelle is known as

the 

aggregation number 

of the micelle.

In the case of amphiphiles in water, the hydrocarbon

chains face inward into the micelle to form, in effect,

their own hydrocarbon environment. Surrounding this

hydrocarbon core are the polar portions of the

amphiphiles associated with the water molecules of

the continuous phase. Aggregation also occurs in

nonpolar liquids. The orientation of the molecules is

now reversed, however, with the polar heads facing

inward while the hydrocarbon chains are associated

with the continuous nonpolar phase. These situations

are shown in Figure 16-4, which also shows some of

the shapes postulated for micelles.

Fig. 16-4

.Some probable shapes of micelles: (

a

) spherical

micelle in aqueous media, (

b

) reversed micelle in

nonaqueous media, and (

c

) laminar micelle, formed at

higher amphiphile concentration, in aqueous media.

It seems likely that spherical micelles exist at

concentrations relatively close to the CMC. At

higher concentrations, laminar micelles have an

increasing tendency to form and exist in

equilibrium with spherical micelles.

As with lyophilic sols, formation of association

colloids is spontaneous, provided that the

concentration of the amphiphile in solution

exceeds the CMC. Amphiphiles may be anionic,

cationic, nonionic, or ampholytic (zwitterionic),

and this provides a convenient means of

classifying association colloids.

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B.

 On the base of the original states of their

constituent parts:

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1.

The Faraday–Tyndall Effect



when a strong beam of light is passed

through a colloidal sol, the path of light is

illuminated (a visible cone formed).



This phenomenon resulting from the

scattering of light by the colloidal particles

.

The same effect is noticed when a beam of

sunlight enters a dark room through a slit when

the beam of light becomes visible through the

room. This happens due to the scattering of

light by particles of dust in the air.

2- Electron microscope

Ultra-microscope has declined in recent years

as it does not able to resolve lyophilic colloids.

so electron microscope is capable of yielding

pictures of actual particles size, shape and

structure of colloidal particles. Electron

microscope has high resolving power, as its

radiation source is a beam of high energy

electrons, while that of optical microscope is

visible light.

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3- Light Scattering

depend on tyndall effect. used to give

information about particle size and shape and

for determination of molecular weight of

colloids. Used to study proteins, association

colloids and lyophobic sols. Scattering

described in terms of turbidity, T Turbidity: the

fractional decrease in intensity due to

scattering as the incident light passes through 1

cm of solution. Turbidity is proportional to the

molecular weight of lyophilic colloid.

Hc / T = 1/M + 2Bc

T

: turbidity

C

: conc of solute in gm / ml of

solution

M

: molecular weight

B

: interaction constant

H

: constant for a particular system

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Grouped under this heading are several properties

of colloidal systems that 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).

1. Brownian Motion



Brownian motion describes the random movement of

colloidal particles. The erratic motion, which may be

observed with particles as large as about 5 μm, was

explained as resulting from the bombardment of the

particles by the molecules of the dispersion medium.

The zig-zag movement of colloidal

particles continuously and randomly



The motion of the molecules cannot be

observed, of course, because the molecules

are too small to see.



The velocity of the particles increases with

decreasing particle size.



Increasing the viscosity of the medium, which

may be accomplished by the addition of

glycerin or a similar agent, decreases and

finally stops the Brownian movement.

2. 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.



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

D

             diffusion coefficient the amount of the material

diffused per unit time across a unit area when 

dc/dx

(conc. gradient) is unity.



The measured diffusion coeffecient can be used to

determine the radius of particles or molecular weight.

3. Osmotic Pressure

The osmotic pressure, π, of a dilute colloidal solution is

described by the 

van't Hoff equation

:

where 

c

 is molar concentration of solute. This equation

can be used to calculate the molecular weight of a

colloid in a dilute solution. Replacing 

c

 with 

cg/M

 in

equation (16-9), in which 

cg

 is the grams of solute per

liter of solution and 

M

 is the molecular weight, we

obtain

where 

g

is the acceleration due to gravity. 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. This

is because Brownian movement becomes

significant and tends to offset 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 the

ultracentrifuge

, which can produce a force one

million times that of gravity.

5. Viscosity



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.



The shapes of particles of the disperse phase

affect the viscosity of colloidal dispersions.



Spherocolloids form dispersions of relatively

low viscosity, whereas systems containing

linear particles are more viscous.

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Particles dispersed in liquid media may become

charged mainly in one of two ways :

•

The first involve selective adsorption of a

particular ionic species present in solution.

This may be an ion added to the solution or,

in the case of pure water, it may be the

hydronium or hydroxyl ion. 

The majority of

particles dispersed in water acquire a

negative charge due to preferential

adsorption of the hydroxyl ion.

•

Second : charges on particles arises from

ionization of groups (such as COOH) that may

be situated at the surface of the particles.

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Consider a solid surface in contact with a polar

solution containing ions, for example, an aqueous

solution of an electrolyte. Furthermore, let us

suppose that some of the cations are adsorbed

onto the surface, giving it a positive charge.

Remaining in solution are the rest of the cations

plus the total number of anions added. These

anions are attracted to the positively charged

surface by electric forces.

In addition to these electric forces, thermal

motion tends to produce an equal distribution of

all the ions in solution.

An equilibrium situation is set up in which

some of the excess anions approach the

surface, whereas the remainder are distributed

in decreasing amounts as one proceeds away

from the charged surface.

At a particular distance from the surface, the

concentrations of anions and cations are equal,

that is, conditions of electric neutrality prevail.

Fig. 15-28

. The electric double layer at the surface of

separation between two phases,showing distribution of

ions. The system as a whole is electrically neutral

.



in figure 15-28 

aa′

 is the surface of the solid.



The adsorbed ions that give the surface its

positive charge are referred to as 

the

potential-determining ions.



Immediately adjacent to this surface layer is

a region of tightly bound solvent molecules,

together with some negative ions, also tightly

bound to the surface. The limit of this region

is given by the 

line bb′ 

in Figure 15-28.



These ions, having a charge opposite to that of the

potential-determining ions, are known as

counterions or gegenions

.



The degree of attraction of the solvent molecules

and counterions is such that if the surface is moved

relative to the liquid, the shear plane is 

bb′

 rather

than 

aa′

.



In the region bounded by the lines 

bb′

 and 

cc′

, there

is an excess of negative ions. The potential at bb′ is

still positive because, as previously mentioned,

there are fewer anions in the tightly bound layer

than cations adsorbed onto the surface of the solid.

Beyond 

cc′, 

the distribution of ions is uniform and

electric 

neutrality is obtained



Thus, the electric distribution at the interface

is equivalent to 

a double layer of charge

, the

first layer(extending from aa′ to bb′) 

tightly

bound

 and a second layer (from bb′ to cc′)

that is more diffuse. The so called diffuse

double layer therefore extends from aa′ to

cc′.

Two situations other than that represented by

Figure 15-28 are possible

:

(a) 

If the counterions in the tightly bound, solvated

layer equal the positive charge on the solid

surface, then electric neutrality occurs at the plane

bb′ 

rather than 

cc′

.

(

b

)

 Should the total charge of the counterions in

the region 

aa′

– 

bb′ 

exceed the charge due to the

potential-determining ions, then the net charge at

bb′ 

will be negative rather than less positive, as

shown in Figure 15-28.

 This means that, in this instance, for electric

neutrality to be obtained at 

cc′

, an excess of

positive ions must be present in the region 

bb′

–

cc′

.

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The potential at the solid surface 

aa′ due to the

potential-determining ion is the electrothermodynamic

Nernst potential

,

 E

, and is 

defined as the difference in

potential between the actual surface and the

electroneutral region of the solution.

potential located at the shear plane 

bb′ is known as 

the

electrokinetic, or

 zeta, potential, δ

. The zeta potential is

defined as the difference in potential 

between the

surface of the tightly bound layer (shear plane) and the

electroneutral region of the solutiona.

•

The zeta potential has practical application in

the stability of systems containing dispersed

particles because this potential, rather than the

Nernst potential, governs the degree of

repulsion between adjacent, similarly charged,

dispersed particles.

•

If the zeta potential is reduced below a certain

value (which depends on the particular system

being used), the attractive forces exceed the

repulsive forces, and the particles come

together. This phenomenon is known as

flocculation.

The movement of a charged surface with

respect to the adjacent liquid phase is the basic

principle underlying four electrokinetic

phenomena :



Electrophoresis



Electroosmosis



Sedimentation Potential



Streaming Potential

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Electrophoresis is the most known electrokinetic

phenomena. It refers to the motion of charged

particles related to the fluid under the influence of an

applied electric field.

If an electric potential is applied to a colloid, the

charged colloidal particles move toward the

oppositely charged electrode

.

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

It is the opposite in principal to that of

electrophoresis.



If the solid is rendered immobile ( by making

particles into a porous plug), the liquid

moves relative to the charged surface. When

potential is applied

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

The sedimentation potential also called the

(Donnan effect)

.



It is the potential induced by the fall of a

charged particle under an external force field.



if a colloidal suspension has a gradient of

concentration (such as is produced in

sedimentation or centrifugation), then a

macroscopic electric field is generated by the

charge imbalance appearing at the top and

bottom of the sample column.

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Differs from electro-osmosis in that the

potential is created by forcing a liquid to flow

through a bed or plug of particles.

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

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 accomplished essentially by two

means:

1.

providing the dispersed particles with an electric

charge.

2.

surrounding each particle with a protective solvent

sheath that prevents mutual adherence when the

particles collide as a result of Brownian movement.



This second effect is significant only in the case of

lyophilic sols.



A lyophobic sol 

is thermodynamically unstable. The particles

in such sols are stabilized only by the presence of electric

charges on their surfaces. The like charges produce a

repulsion that prevents coagulation of the particles. If the

last traces of ions are removed from the system by dialysis,

the particles can agglomerate and reduce the total surface

area, and, owing to their increased size, they may settle

rapidly from suspension. Hence, addition of a small amount

of electrolyte to a lyophobic sol tends to stabilize the system

by imparting a charge to the particles. Addition of

electrolyte beyond that necessary for maximum adsorption

on the particles, however, sometimes results in the

accumulation of opposite ions and reduces the zeta

potential below its 

critical value

.



Coagulation also result from mixing of oppositely charged

colloids.



Lyophilic and association colloids 

are

thermodynamically stable and The addition

of an electrolyte to a lyophilic colloid in

moderate amounts does not result in

coagulation, as was evident with lyophobic

colloids. If sufficient salt is added, however,

agglomeration and sedimentation of the

particles may result. This phenomenon,

referred to as 

salting out

.

•

This is obtained by:

1- Addition of large amounts of electrolytes

-

Anions arranged in a decreasing order of

precipitating power: 

citrate > tartrate > sulfate >

acetate > chloride> nitrate > bromide > iodide

-

The precipitation power is directly related to the

hydration of the ion and its ability to separate

water molecules from colloidal particles

2- addition of less polar solvent

-

e.g. alcohol, acetone

-

The addition of less polar solvent renders the

solvent mixture unfavourable for the colloids

solubility

Coacervation:

the process of mixing negatively and positively

charged hydrophilic colloids, and hence the

particles separate from the dispersion to form a

layer rich in the colloidal aggregates

(coacervate)

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:

•

Sensitization: 

the addition of small amount of

hydrophilic or hydrophobic colloid to a

hydrophobic colloid of opposite charge tend to

sensitize (coagulate) the particles.

•

Polymer flocculants can bridge individual

colloidal particles by attractive electrostatic

interactions.

•

For example, negatively-charged colloidal silica

particles can be flocculated by the addition of a

positively-charged polymer

.

Protection: 

the addition of large amount of

hydrophilic  colloid 

(protective colloid)

 to a

hydrophobic colloid tend to stabilize the

system.

This may be due to:

The hydrophile is adsorbed as a

monomolecular layer on the hydrophobic

particles.