Transcript Colloidal

Colloid
An Introduction
Kausar Ahmad
Kulliyyah of Pharmacy
http://staff.iiu.edu.my/akausar
Contents
Lecture 1:

Types of colloids

Classification based on size

Types of dispersions
-----------------------------------------------------Lecture 2:

Types of emulsions

Emulsification factors

Properties of colloids
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Colloidal System

Particle size below 1 mm

High specific surface area
 Discrete
particles dispersed in a
different medium

In pharmaceutical emulsions or
suspensions, particle size ranges from
colloidal to visible or coarse.
Types of Colloids
Type
Continuous
Disperse phase
phase
Emulsion: o/w Oil
Water
Emulsion: w/o Water
Oil
Suspension
Aerosol
Solid
Solid or liquid
Water or oil
air
Others
Multiple emulsion: w/o/w, o/w/o
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Classification Based on Size
Class
Size
Examples
Molecular
dispersion
< 1.0 nm
Oxygen gas, ordinary
ions, glucose
Colloidal
dispersion
1.0 nm to 0.5 mm Silver sols, natural and
synthetic polymer
latices
Sand, pharmaceutical
emulsions &
dispersions, red blood
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cells
Coarse > 0.5 mm
dispersion
Classification of dispersed systems

hydrophilic colloidal dispersion (in water)


lyophilic colloids (lyo=solvent)


surfactant micelles and phospholipid vesicles, also
known as association colloids.
colloidal systems are proteins, rubber, gelatin and
gums.
lyophobic colloids

gold, silver and sulfur.
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…..or Sols….another definition

Sol – refers to any colloidal system in which the
dispersion medium is a liquid.

Lyophilic sol – a sol consisting of a dispersed phase
which has an affinity for the continuous phase.


This means that the colloid is readily formed e.g.
starch in water.
Lyophobic sol – a sol which is solvent-repelling, such
that the disperse phase has little or no attraction for the
dispersion medium

e.g. gold in water.
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Use of Colloidal Phenomena

Detergency

Dewatering of sludges via coagulation

Emulsion polymerisation

Natural phenomena i.e. milk (casein)
 Demulsification
example?
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Detergency

Most important products using surfactants
 Main
component is surfactant

Involves in adsorption, wetting,
emulsification and dispersion

Wetting of substrate ->soil-removing
process ->preventing soil redeposition
(PEG)
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Pharmaceutical suspensions

Coarse dispersions
lyophobic colloids (lyo=solvent)

Suspension: solid in liquid

prepared from water-insoluble drugs for delivery orally or
by injection (intra-muscular) in liquid vehicle.




E.g. Oral suspensions, topical applications,
Injectables: intra-muscular
Surfactant/Dispersant to wet the particles
Stabilisation by electric repulsive force and steric
hindrance effect
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Pharmaceutical Emulsions

Emulsion: liquid drug in liquid vehicle: o/w or
w/o

Main function of emulsion is to provide vehicles
for drug delivery and parenteral nutrition. The
drug is dissolved in the water or oil phase.


E.g. Parenterals, creams, lotions
Surfactant/Emulsifier reduces the interfacial
energy and the emulsion becomes
thermodynamically stable
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Preparing a Dispersion
1.
Particle size reduction
aggregates may require considerable mechanical energy to
break them down completely - to the point when the surface
of each primary particle is available to the wetting liquid.
2.
Wetting of the powder
this is necessary not to wet external surfaces but also for
displacing air between the internal clusters.
2.
Dispersing by using charged bulky surfactants
e.g. sodium oleate, sodium or ammonium caseinate
3.
Modifying the viscosity to minimise sedimentation
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(see Stoke’s Law)
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Properties of dispersing agents

Adsorption of surfactants at the solid/liquid
interface.

Highly charged

Can provide steric hindrance
END OF LECTURE 1 OF 2
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END OF LECTURE 1 OF 2
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Types of Emulsions
 Macroemulsion
 Nanoemulsion
 Microemulsion
 Multiple
emulsion
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Nanoemulsion and Microemulsion

Nanoemulsions

cover the size range of 50-200 nm

Microemulsions
 usually
in the size range of 5-50 nm

long term physical stability against creaming,
flocculation and coalescence

Due to their small size they enhance penetration,
spreading and will give uniform distribution on the
substrate on which they are applied.

application in personal care products and cosmetics,
agrochemicals, pharmaceuticals, household products
etc.
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Methods of Preparation

Nanoemulsions are easily formulated using highpressure homogenizers with proper choice of
surfactants and/or polymers.

The production of microemulsions may employ the
Phase Inversion Temperature (PIT) principle.

These emulsions are stabilised through
steric stabilization and
by the thickness of
the adsorbed layer.
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Emulsification Factors

Concentration of dispersed/oil phase

Types and concentrations of surfactants

Emulsifying temperature especially for non-ionic
surfactants

Type of
homogeniser/emulsifying
equipment
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Multiple
Emulsion

Disperse phase contains droplets of another phase.

Exist as o/w/o or w/o/w.

Prepared through a double homogenization process or a
one step procedure using the PIT.

Both are important for drug delivery.
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Example of w/o/w emulsion
for drug delivery by intra-muscular route

advantage: slow-release because drug has to
diffuse through oil

disadvantage: viscosity of medium is high

solution: to disperse the w/o in aqueous
medium.

On injection, the aqueous phase dissipates
rapidly leaving behind the w/o.
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Multiple emulsion
An example from research
Evaluation of process factors in oil-water-oil multiple emulsion method
for flavor encapsulation
Y. H. CHO and J. Park. Dept. of Biotechnology, Yonsei University, 134, Shinchondong, Seodaemoon-gu, Seoul, 120-749, South Korea

Multiple emulsion method is proposed for the encapsulation of
sensitive ingredients since it is carried out in mild conditions and
without any toxic compounds. This method has been applied in
pharmaceutics and chemical industry, while it is relatively new to flavor
and food industry.

Research on multiple emulsion, especially O/W/O type is limited because of the
practical difficulty in preparing a stable emulsion.
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Exercise: What are the factors involved for
preparing stable O/W/O multiple emulsion?
gum arabic to maltodextrin (0:10-5:5)
Homogeniser
microfluidizer
(34-83 MPa)
piston-type homogenizer
(20 MPa)
This O/W emulsion was emulsified in molten hydrogenated palm kernel
oil containing 5% emulsifier at 13,500 rpm using Ultra-TurraxTM.
Selected emulsifiers were Span 80, Tween 80, polyglycerin
polylysinoleate (PGPR) and glycerin monostearate (ES-95®).
O/W/O multiple emulsion was solidified in ethanol:water (9:1) solution.
Solid microcapsules were collected by filtration and freeze-dried. The
physical properties and morphology of microspheres were determined.
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OBSERVATIONS

Microfluidizer (at 70 MPa) produced more stable
emulsion, as it produced small uniform droplet.

Increasing gum arabic content created highly viscous
emulsion, which subsequently resulted in stable O/W
emulsion.

The stability of O/W/O multiple emulsion was highly
affected by the type of emulsifiers and the most stable
emulsion was prepared using the blend of Span 80 and
PGPR.

Microcapsules were 273.5 mm in mean diameter,
spherical in shape, and had a porous structure.
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Multiple Emulsion for Pharmaceuticals
Examples
1.
Sandostatin LARTM Depot – Novartis (hypothalamic
hormones analogue)

2.
Control of hypersecretion at the site of the tumor
where hormone overproduction starts
Human NutropinTM Depot – Alkermes/Genentech
(human insulin suspension)

somatropin (rDNA origin) for injectable suspension long-acting dosage form of recombinant human
growth hormone (rhGH).
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Multiple emulsion
Pharmaceutical Problems

Rapid release during the
first day
typically accounts for 1080% of the total drug
loading. This ‘initial burst’
poses a toxicity threat
and is a major hurdle for
the development of
microspheres.

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Very slow (close to zero)
release period after the
initial burst period.
This can last for weeks and
is referred to as the ’lagtime’. During this induction
period, the patient is not
effectively treated due to
lack of drug release.
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Properties of System
Colloidal
 Particles not resolved
by ordinary
microscope


visible in electron
microscope
Particles diffuse
very slowly
Coarse
Particles visible under
microscope

Do not pass through
filter paper

Particles do not
diffuse
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Optical Properties of Colloids
Faraday-Tyndall effect
– when a strong beam of light is passed through a colloidal
sol, a visible cone, resulting from the scattering of light by
the colloidal particles is formed.
Turbidity
– as a result of light scattering caused by fine
particles obstructing the path of light

Based on this property, the investigation on
molecular weight of the colloid is possible via light
scattering studies.
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Kinetic Properties of Colloids

Brownian motion – arises from bombardment
of dispersed particles by molecules of dispersion
medium.

Diffusion – particles diffuse spontaneously from
region of high to low concentration

Osmotic pressure: allows the calculation of
molecular weight of colloid

Sedimentation: as given by Stoke’s law

Viscosity – resistance to flow under applied
stress.
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References
1.
PC Hiemenz & Raj Rajagopalan, Principles of Colloid
and Surface Chemistry, Marcel Dekker, New York
(1997)
2.
HA Lieberman, MM Rieger & GS Banker,
Pharmaceutical Dosage Forms: Disperse Systems
Volume 1, Marcel Dekker, New York (1996)
3.
F Nielloud & G Marti-Mestres, Pharmaceutical
Emulsions and Suspensions, Marcel Dekker, New York
(2000)
J Kreuter (ed.), Colloidal Drug Delivery Systems,
Marcel Dekker, New York (1994)
4.
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