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COLLEGE OF PHARMACY Dr. Mohammad Javed Ansari, PhD. Contact info: [email protected] PHARMACEUTICS II (PHT 312)

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Page 1: PHARMACEUTICS II COLLEGE OF (PHT 312) PHARMACY · PDF file•Lyophilic colloids ... •Stability of Colloid Systems ... •If all particles in a colloidal system are of (nearly) the

COLLEGE OF

PHARMACY

Dr. Mohammad Javed Ansari, PhD.

Contact info: [email protected]

PHARMACEUTICS II (PHT 312)

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OBJECTIVES OF THE LECTURE

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

• What are disperse systems?

• What are various types of colloidal dispersion?

• What are features of colloidal dispersion?

• What are various colloidal formulations?

• How colloids are prepared?

• How colloids are purified?

• What are different properties of colloids?

• What are stability problems of colloids?

• How colloids are stabilized?

• What are pharmaceutical applications of colloids?

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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.

• Ultra filtration and Dialysis, Electro-dialysis

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

kinetic).

• Stability of Colloid Systems

• Application of Colloids

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

• Classified based on size of dispersed phase

•Coarse dispersion > 1 m suspension & emulsion

•Colloidal dispersion 1 nm- 1 m 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.

Pharmaceutical Colloidal: Definition & Features

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• 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.

Pharmaceutical Colloidal: Definition & Features

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Colloidal Systems in Nature

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Classified based upon the interaction / affinity between

dispersed colloids and dispersion medium

1. Lyophilic colloids = Solvent loving colloids.

2. Lyophobic colloids = Solvent hating colloids

3. Amphiphilic colloids = both loving colloids

• These colloids have affinity with both water as well as

Lipids therefore these are both hydrophilic and

Lipophilic.

• Based upon nature of dispersed colloids in liquids

• Liquid: colloidal emulsion

• Solid: colloidal suspension

TYPES OF COLLOIDAL DISPERSIONS

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LYOPHILIC COLLOIDS: FEATURES & PREPARATION

• Have affinity with dispersion medium.

• Called as hydrophilic colloids when media is water

• Spontaneous: these colloids are spontaneously formed

by dispersing the material in the solvent.

• Organic substance like gelatin, gum, starch, egg, albumin

etc. pass readily into water to give colloidal solution.

• Stable: these colloids are very stable (don’t need any

stabilizing agents) and do not precipitate/coagulate easily.

However addition of very large quantities of electrolytes

can cause particles to precipitate.

• Reversible : If solvent is evaporated, the sol can be made

again by simply re-mixing with solvent.

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•The colloidal particles have very little affinity, if any, for the

dispersion medium. Eg. In organic materiasl like Metals, their

hydroxides and sulphides.

• Don’t form spontaneously (need special techniques)

• 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.

LYOPHOBIC COLLOIDS: FEATURES & PREPARATION

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B- Condensation method:

Sub-colloidal particles are caused to aggregate into

colloidal ones.

- condensation 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

- condensation by chemical reaction: Reduction, oxidation

or hydrolysis

e.g. oxidation of hydrogen sulfide leads to formation of

colloidal sulfur.

LYOPHOBIC COLLOIDS: FEATURES & PREPARATION

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•Amphiphiles or surfactants (surface active

agents) are molecules characterized by having a

hydrophilic head and a lipophilic tail.

•When dispersed in a liquid at low concentration

the amphiphiles exist separately and are in a sub-

colloidal 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.

AMPHIPHILIC OR ASSOCIATION COLLOIDS

FEATURES & PREPARATION

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Ultra filtration: Filtration using ultra filters (filters with

very small pores). Colloids can cross normal filter papers.

Dialysis / Electro-dialysis: Removal of sub colloidal

species (electrolytes / impurities) by putting the colloidal

mixture in a dialysis bag.

•An electrical potential may be used to increase the rate of

movement of ionic impurities through a dialysis membrane.

Pharmaceutical application of dialysis

Haemodialysis:

Small molecular weight impurities from

the body (blood) are removed by passage

through a membrane.

Purification / Separation of colloids

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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.

Large specific surface area results in many unique

properties of colloidal dispersions.

Optical properties of colloids. eg. Tyndall (Faraday) Effect

Kinetic properties of colloids eg. Brownian motion,

diffusion, osmosis, viscosity etc.

Electrical Properties of Colloids eg. Zeta potential

Electro-kinetic Properties of Colloids eg. Electrophoresis

Properties of Colloids

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Tyndall Effect (Light scattering Effect )

John Tyndall, a physicist observed this

phenomenon in 1869.

He observed that when a beam of light is

allowed to pass through a colloidal solution, the

path of light gets illuminated. (which was due to

scattering of light by colloidal particles).

To scatter the Light, size of the colloidal

particles must be in range within the wavelength

range of visible light i.e. 200-700 nm.

High wavelength light (Blue) is scattered more

than short wavelength light (orange & red).

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Tyndall Effect (Light scattering Effect )

Page 17: PHARMACEUTICS II COLLEGE OF (PHT 312) PHARMACY · PDF file•Lyophilic colloids ... •Stability of Colloid Systems ... •If all particles in a colloidal system are of (nearly) the

Tyndall Effect (Light scattering Effect )

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Tyndall Effect (Light scattering Effect )

The intensity of the scattered light depends on

the difference between the refractive indices of the

colloidal particles and the dispersion medium.

Lyophilic colloidal particles are highly solvated,

which results into lower difference in refractive

index of two phases therefore Tyndall effect is less

pronounced in lyophilic colloids.

In case of lyophobic colloidal solution, the

difference in refractive index is quite large and

therefore it shows pronounced Tyndall effect.

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Tyndall Effect (Light scattering Effect ) Light scattering measurements are of great value for

estimating particle size and shape and number of particles

per unit weight or volume.

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.

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• Properties which are related to the motion of particles

with respect to the dispersion medium

•1. Brownian motion

Zig zag movement of the colloidal particles.

Random collision (accident) of the colloidal particles with

the molecules of the dispersion medium.

The velocity of the particles increase with decreasing

particle size.

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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.

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2. Diffusion 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

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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 =

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3. Osmotic Pressure:

If a solution and a solvent are separated by a semi

permeable 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

Page 25: PHARMACEUTICS II COLLEGE OF (PHT 312) PHARMACY · PDF file•Lyophilic colloids ... •Stability of Colloid Systems ... •If all particles in a colloidal system are of (nearly) the

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.

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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.

Page 27: PHARMACEUTICS II COLLEGE OF (PHT 312) PHARMACY · PDF file•Lyophilic colloids ... •Stability of Colloid Systems ... •If all particles in a colloidal system are of (nearly) the

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)

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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

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Electrical Properties of Colloids

These are properties, which depend on, or are affected

by the presence of a charge on the surface of a colloid.

Colloids dispersed in Liquid media may become

charged mainly due to:

1. Adsorption of a particular ionic species present in

solution such as hydronium or hydroxyl ion.

Seen in most LYOPHOBIC COLLOIDS.

2. Transfer of electrons- or ions from the

substances of high dielectric constant to those of

lower one.

As a result when a colloid possesses a higher

dielectric constant than its dispersion medium, it will

acquire a positive charge and vice-versa.

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Electrical Properties of Colloids

3. Ionization of functional groups of colloids (such as

COOH, SO4) as seen in most LYOPHILLIC COLLOIDS.

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

(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, protein

exist as zwitterion, which is electrically neutral, both

groups are ionized (Solubility of the protein will be

minimum hence precipitation will be facilitated).

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Electro-kinetic phenomena Electrophoresis

•The movement of a charged colloidal particles under the

influence of an applied potential difference.

•Negatively charged colloids will move towards Anode

whereas positively charged will move towards Cathode.

•Lyophilic colloids may not show electrophoresis due to

absence of charges on colloids.

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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 & association colloids:thermodynamically stable.

•The addition of an electrolyte to a lyophilic colloid in

moderate amounts does not result in coagulation.

•Lyophobic colloids are thermodynamically unstable.

Thermodynamic stability of lyophobic colloids may be

increased by an addition of relatively small amount of

surface active substances (surfacants) lowering the interfacial

energy of the system.

Or by adding small amount of polymers to cover colloids so

that these don’t feel attractions (Steric stabilization).

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Stability of Colloid Systems

The stability of hydrophobic colloids depends on the zeta

potential which is due to electrical double layer of colloids:

•when the absolute value of zeta potential is above ±30 mV

the colloidal dispersions are supposed to be stable due to

mutual repulsion (electrostatic stabilization).

•Hydrophobic colloids will aggregate and precipitate if their

electrical charge is removed / disturbed.

•Therefore addition of small amount of electrolyte or

oppositely charged colloid may lead to coagulation /

agglomeration due to decrease in the zeta potential

(repulsion index).

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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, liposomes, micelles, nanoparticles, and nanoemulsions

and microemulsions.

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Application of Colloids

• Hydrogels are cross-linked or interwoven polymeric

networks, which absorb and retain large amounts of water.

• Target Site specific controlled drug delivery systems.

Environment sensitive hydrogels have the ability to sense

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

specific metabolite and release their load.

• Liposomes:lipid bilayer vesicle having aqueous cavity.

• Nanocapsules are sub-microscopic colloidal carrier systems

composed of an oily or an aqueous core surrounded by a

thin polymer membrane.

• Nanoemulsions / microemulsions are consist of very fine

oil-in-water or water in oil dispersions, having droplets

diameter smaller than 100 nm.

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Application of Colloids

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GOOD LUCK ..