COLLEGE OF

PHARMACY

Dr. Mohammad Javed Ansari, PhD.

Contact info: javedpharma@gmail.com

PHARMACEUTICS II

(PHT 312)

31 O

cto

ber

201

5

31 October 2015

OBJECTIVES OF THE LECTURE

• At the end of this lecture, you will be aware of:

• What are disperse systems?

• What are various types of disperse systems?

• What are colloidal and coarse dispersions?

• What are various colloidal formulations?

• What are advantages / disadvantages of colloidal formulation?

• What are various properties of colloids?

• What are stability problems of colloids?

• How colloids are stabilized?

• How colloids are prepared?

31 October 2015

LECTURE OUTLINES

• Definition of Colloidal dispersion.

• Colloids in nature

• TYPES OF COLLOIDAL SYSTEMS

• Lyophilic colloids

• Lyophobic colloids

• Amphiphilic or Association Colloids

• METHOD OF PREPARATION

• Dispersion method (mill, Ultrasonic treatment)

• Condensation method: (super-saturation, chemical reaction)

• Purification / Separation of colloids.

• Dialysis, Electro-dialysis and Ultra filtration

• Properties of Colloids (Optical, Kinetic, Electrical, Electro-

kinetic).

• Stability of Colloid Systems

• Application of Colloids

31 October 2015

Dispersed systems consist of particulate matter known as dispersed phase, dispersed throughout a continuous or dispersion medium.

Dispersed systems are classified according to particle size

Coarse dispersion > 1 m suspension & emulsion

Colloidal dispersion 1 nm – 500 nm colloids

Colloidal System is defined as the heterogeneous biphasic system in which dispersed phase is subdivided into nano size range (1-1000 nanometer).

Nanoparticles are small colloidal particles, but not all small colloidal particles are nanoparticles.”

If all particles in a colloidal system are of (nearly) the same size the system is called monodisperse; in the opposite cases the systems are heterodisperse /polydisperse.

31 O

cto

ber

201

5

• It is not necessary for the units of a colloidal system to be discrete (separate particles)

• Therefore continuous network structures, the basic units of which are of colloidal dimensions also fall in this class (e.g. porous solids, gels and foams).

• Nor it is necessary for all three dimensions to be in the colloidal range.

• Films (only one dimension) and fibers (only two dimensions) are in nano range, may also be classified as colloidal.

• Eg. Hydrophillic colloids like alginates, agar gelatin, pectin, cellulose derivatives and polymers.

Colloidal Systems 31

Oct

ob

er 2

015

Colloidal Systems 31

Oct

ob

er 2

015

TYPES OF COLLOIDAL SYSTEMS AND THEIR

METHOD OF PREPARATION

Depending upon the interaction between dispersed colloids and dispersion medium, they are classified as

1. Lyophilic colloids = solvent loving colloids.

• There is an affinity between colloidal particles and dispersion medium.

• Spontaneous: Colloids are spontaneously formed by dispersing the material in the solvent e.g. dispersion of acacia or gelatin in water (hydrophilic colloid) or nitrocellulose in alcohol ether (collodion).

• Reversible : If solvent is evaporated, the sol can be made again by simply re-mixing with solvent.

• Very stable: don’t need any stabilizing agents.

31 O

cto

ber

201

5

2. Lyophobic colloids = solvent hating colloids • The colloidal particles have very little affinity, if any,

for the dispersion medium. Eg. Metals, their hydroxides and sulphides.

• Special technique needed for their preparation. • Unstable: require stabilizing agents. • Irreversible: once precipitated, don’t return.

A- Dispersion method: Coarse particles are reduced in size by the use of colloidal mill or ultrasonics.

Colloidal mill: coarse material is sheared in a narrow gap between a static cone and a rapid rotating cone. Ultrasonic treatment: the passage of ultrasonic waves through a dispersion medium.

TYPES OF COLLOIDAL SYSTEMS &THEIR METHOD OF PREPARATION 31

Oct

ob

er 2

015

B- Condensation method:

Sub-colloidal particles are caused to aggregate into

colloidal ones.

- By super-saturation: high degree of initial super-

saturation followed by growth of nuclei (by change of

solvent or reduction of temperature).

e.g. addition of water to saturated alcoholic solution

of sulfur

- By chemical reaction: Reduction, oxidation or

hydrolysis

e.g. oxidation of hydrogen sulfide leads to formation

of colloidal sulfur

TYPES OF COLLOIDAL SYSTEMS &THEIR METHOD OF PREPARATION 31

Oct

ob

er 2

015

3. Amphiphilic or Association Colloids

Amphiphiles or surface active agents are molecules

characterized by having a hyrophilic head and a

lipophilic tail.

When present in a liquid at low concentration the

amphiphiles exist separately and are in a

subcolloidal size range.

When the concentration exceeds a certain level

(CMC) the molecules aggregate to form micelles

(contain 50 or more monomers).

Micelles lie within the colloidal size range.

TYPES OF COLLOIDAL SYSTEMS &THEIR METHOD OF PREPARATION 31

Oct

ob

er 2

015

Purification / Separation of colloids

Dialysis

Colloidal particles are not retained by conventional filter papers but are too large to diffuse through the pores of semipermeable (dialysis) membranes of collodion or cellophane.

The pore size will permit only the passage of smaller particles (molecular range). This process is known as dialysis.

The colloidal material is retained while the subcolloidal material is distributed equally in both compartments.

By continually removing the liquid in the acceptor cell it is possible to obtain colloidal material free from subcolloidal contaminants

31 O

cto

ber

201

5

Electro-dialysis

An electrical potential may be used to increase the rate of movement of ionic impurities through a dialysis membrane.

Ultrafiltration

By applying pressure or suction the solvent and molecular particles are forced across the membrane but the larger particles are retained.

Pharmaceutical application of dialysis

Haemodialysis: Small molecular weight impurities from the body (blood) are removed by passage through a membrane.

Purification / Separation of colloids 31

Oct

ob

er 2

015

Due to their small size they do not settle out of solution.

Particles lying in the colloidal size range possess an

enormous surface area compared with the surface area of an

equal volume of larger particles.

In order to compare surface area of different systems we

use the term specific surface area (= surface area per unit

weight or volume of material).

Large specific surface area results in many unique properties

of colloidal dispersions.

Tyndall (Faraday) Effect

Brownian motion, diffusion,

osmosis, viscosity etc.

Electrical Properties of Colloids eg. Zeta potential

Electro-kinetic Properties of Colloids eg. Electrophoresis

Properties of Colloids 31

Oct

ob

er 2

015

Light scattering / Tyndall (Faraday) Effect When a strong beam of light is passed through a colloidal sol some of the light may be absorbed, some is scattered and the remainder is transmitted undisturbed through the sample. Because of the scattered light the sol appears turbid: This is known as the Tyndall effect. Light scattering measurements are of great value for estimating particle size and shape and number of particles per unit weight or volume.

Properties of Colloids 31

Oct

ob

er 2

015

31 October 2015

Antimony and arsenic trisulfide change from red to yellow as the

particle size is reduced from coarse to colloidal size.

GOLD CHLORIDE HAS A DEEP RED COLOR, SILVER IODIDE IS YELLOW.

EVALUATION OF COLLOIDS

Ultra-microscope: Allows the examination of the light spots

responsible for the Tyndall cone.

The light spots corresponding to the particles are counted and

average particle size may be calculated.

Electron Microscope: It is capable of taking pictures of the

actual particles even those approaching molecular dimensions.

It is used to observe size, shape and structure of colloidal

particles.

31 O

cto

ber

201

5

Properties which are related to the motion of particles with respect to the dispersion medium 1. Brownian motion 2. Diffusion Particles spontaneously diffuse from a region of higher concentration to a region of lower concentration until the concentration of the system is uniform throughout. Diffusion is a direct result of Brownian movement.

Random movement of the colloidal particles. The erratic motion is due to the random collision (accident) of the colloidal particles with the molecules of the dispersion medium. The velocity of the particles increase with decreasing particle size.

31 O

cto

ber

201

5

The rate of diffusion is expressed by Fick's first law, = - DA

dm the amount of substance diffusing in time dt across a plane of area A is directly proportional to concentration gradient dc/dx (the change of concentration dc with distance traveled dx). D is known as the diffusion coefficient (area per unit time). The negative sign is because diffusion occurs in the direction of decreasing concentration.

dm dt

dc dx

31 O

cto

ber

201

5

Diffusion coefficient obtained from Fick's law can be

used to obtain the radius of approximately spherical

colloidal particles

D = Diffusion coefficient obtained from Fick's law

R = Molar gas constant

T = Absolute temperature

= Viscosity of the solvent

r = radius of the spherical particle

N = Avogadro's number

The diffusion coefficient may be also used to obtain the

molecular weight of approximately spherical

molecules, such as egg albumin and hemoglobin.

RT 6 r N

D =

31 O

cto

ber

201

5

3. Osmotic Pressure:

If a solution and a solvent are separated by a

semipermeable membrane the tendency to equalize

concentration on either side of the membrane results in a

net diffusion of solvent across the membrane.

The pressure necessary to balance the osmotic flow is

called the osmotic pressure.

Osmotic pressure can be used to determine the molecular

weight using the following equation (derived from Van’t Hoff equation)

C = Concentration of solution T = Absolute temperature

M = Molecular weight R= Gas constant

B = Constant depending on the degree of interaction

between dispersed phase and dispersion medium

C

RT M

= + B C

31 O

cto

ber

201

5

4. Sedimentation The velocity v of sedimentation of spherical particles is

given by Stoke's law

v =

d = diameter of the particles

o = density of the medium

= density of the spherical colloidal particles.

g = acceleration due to gravity.

= viscosity of the medium

If the particles are only subjected to the force of gravity,

then the lower size limit of particles obeying Stoke's

equation is about 0.5 m.

d2 ( - o) g 18

This is because Brownian movement ends to counteract sedimentation due to gravity and promotes mixing.

31 O

cto

ber

201

5

5. 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.

The present section is concerned with:

the flow properties of dilute colloidal systems

the manner in which viscosity data can be used

to obtain the molecular weight of the disperse

phase.

Viscosity studies also provide information regarding

the shape of the particles in solution.

31 O

cto

ber

201

5

Einstein developed an equation of flow applicable to

dilute colloidal dispersions of spherical particles:

= o (1 + 2.5 )

o = viscosity of the dispersion medium

= viscosity of the dispersion medium when the

volume fraction of colloidal particles is

The volume fraction is defined as the volume of the

particles divided by the total volume of the dispersion. Several viscosity coefficients may be defined with

respect to this equation:

relative viscosity (rel)

specific viscosity (sp)

intrinsic viscosity (int)

31 O

cto

ber

201

5

Relative viscosity: rel = /o = 1 + 2.5

Specific viscosity: sp= - o /o = rel -1= 2.5

Since volume fraction is directly related to concentration

sp /C = K

C = Concentration expressed in grams of colloidal

particles per 100 ml of total dispersion.

If sp/C is plotted against C and the line is extrapolated

to infinite dilution, the intercept is known as the

intrinsic viscosity int

31 O

cto

ber

201

5

Electrical Properties of Colloids

These are properties, which depend on, or are affected

by the presence of a charge on the surface of a

particle.

Particles dispersed in Liquid media may become

charged mainly due to:

[1] The surface active 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.

[2] The charges on particles, which arise from

ionization of groups (such as COOH) which may

be situated at the surface of the particle. In

these cases, the total charge is a function of pH.

31 O

cto

ber

201

5

Electrical Properties of Colloids The charge carried by colloid protein molecules will depend on the pH of the dispersion medium.

(a)In alkaline solution: The carboxylic acid groups of the protein

molecules will exist as carboxylate anions.

NH2 --- R ---COO-

(b) In acid solution: The amino groups of the molecules will be

protonated: NH3+ ---R --- COOH

At, alternative pH, known as the isoelectric

point, the protein exist as zwitterion, which is

electrically neutral, both groups are ionized.

The solubility of the protein is at a minimum at

its isoelectric point and therefore precipitation is

facilitated at this pH. NH3+ --- R --- COO-

31 O

cto

ber

201

5

Electrical Properties of Colloids…

[3] The charge on a particle surface may be arised

when there is a difference in dielectric constant

between the particle and its dispersion medium.

There will be a transfer of electrons- or ions from the

substances of high dielectric constant to those of

lower one.

As a result when a particle possesses a higher

dielectric constant than its dispersion medium, it will

acquire a positive charge and vice-versa.

31 O

cto

ber

201

5

Electro-kinetic phenomena

The movement of a charged colloidal particles with respect

to adjacent liquid phase is the principle of the electro-kinetic

phenomena (electrophoresis).

Electrophoresis

Involves the movement of a charged particle

through a liquid under the influence of an

applied potential difference.

An electrophoresis cell, fitted

with two electrodes, contains

the dispersion. When a

potential is applied across the

electrodes, the Electronegative

colloid particles migrate to the

oppositely charged electrode.

31 O

cto

ber

201

5

Stability of Colloid Systems

The presence and magnitude, or absence of a charge on a

colloidal particle is an important factor in the stability of

colloidal systems.

Lyophilic and association colloids are thermodynamically

stable.

The addition of an electrolyte to a lyophilic colloid in

moderate amounts does not result in coagulation.

A lyophobic sol is thermodynamically unstable.

The particles in such system are stabilized only by the

presence of electrical charges on their surfaces.

Stability is accomplished essentially by 2 means:

• providing the dispersed particles with an electric charge

• surrounding each particle with a protective solvent

sheath which prevents mutual adherence when the

particles bump as a result of Brownian movement.

31 O

cto

ber

201

5

Stability of Colloid Systems

The stability of hydrophobic colloids depends on

the zeta potential:

when the absolute value of zeta potential is above

50 mV the dispersions are very stable due to

mutual electrostatic repulsion.

when the zeta potential is close to zero the

coagulation (formation of larger assemblies of

particles) is very fast and this causes a fast

sedimentation.

Therefore, the addition of a small amount of

electrolyte to a lyophobic sol tends to stabilize the

system by imparting a charge to the particles.

31 O

cto

ber

201

5

Application of Colloids

• Colloids are extensively used for modifying the

properties of pharmaceutical agents.

• Colloidal drugs exhibit substantially different

properties when compared with traditional forms of

the dosage forms.

• The most common property that is affected is the

solubility of a drug.

• Another important pharmaceutical application of

colloids is their use as drug delivery systems.

• The most often used colloid- type delivery systems

include hydrogels, microspheres, liposomes, micelles,

nanoparticles, and nanocrystals.

31 O

cto

ber

201

5

Application of Colloids

• Hydrogels can be defined as cross-linked or interwoven

polymeric networks, which absorb and retain large

amounts of water.

• Synthetic microgels consist of a crosslinked polymer

network that provides a depot for loaded drugs, protection

against environmental hazards.

• Hydrophilic and biocompatible microgels could provide a

unique mode for targeted delivery of encapsulated drugs

via blood.

• Environment sensitive hydrogels have the ability to sense

changes in the pH, temperature, or the concentration of a

specific metabolite and release their load as a result of

such a change; these hydrogels can be used as site

specific controlled drug delivery systems

31 O

cto

ber

201

5

Application of Colloids

• Microparticles refers to a particle with a diameter of 1–1000

μm, irrespective of the precise interior or exterior

structure.

• Microparticles, may be classified as “microspheres” specifically refers to spherical microparticles and

• the “microcapsules” which have a core surrounded by a

material which is distinctly different from that of the core.

The core may be solid, liquid, or even gas.

• Nanocapsules are sub-microscopic colloidal carrier

systems composed of an oily or an aqueous core

surrounded by a thin polymer membrane

31 O

cto

ber

201

5

Application of Colloids

• Microemulsions are excellent candidates as potential drug

delivery systems because of their improved drug

solubilization, long shelf life, and ease of preparation and

administration.

• In contrast to Microparticles, which demonstrate distinct

differences between the outer shell and core,

microemulsions are usually formed with more or less

homogeneous particles.

• Three distinct Microemulsions- oil external, water external,

and middle phase- can be used for drug delivery,

depending upon the type of the dug and the site of action.

• Nanoemulsions consist in very fine oil-in-water

dispersions, having droplets diameter smaller than 100

nm.

31 O

cto

ber

201

5

Application of Colloids

31 O

cto

ber

201

5

GO

OD

LU

CK

..

31 October 2015