1. Colloid An Introduction
Kausar Ahmad
Kulliyyah of Pharmacy

2. 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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3. Colloidal System Discrete particles dispersed in a different medium
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.

4. Types of Colloids Type Disperse phase Continuous phase Emulsion: o/w
Oil
Water
Emulsion: w/o
Suspension
Solid
Water or oil
Aerosol
Solid or liquid
air
Others
Multiple emulsion: w/o/w, o/w/o
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5. Classification Based on 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
Coarse dispersion
> 0.5 mm
Sand, pharmaceutical emulsions & dispersions, red blood cells
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6. Classification of dispersed systems
hydrophilic colloidal dispersion (in water)
surfactant micelles and phospholipid vesicles, also known as association colloids.
lyophilic colloids (lyo=solvent)
colloidal systems are proteins, rubber, gelatin and gums.
lyophobic colloids
gold, silver and sulfur.
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7. …..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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8. Use of Colloidal Phenomena
Detergency
Dewatering of sludges via coagulation
Emulsion polymerisation
Natural phenomena i.e. milk (casein)
Demulsification example?
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9. Detergency Main component is surfactant
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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10. 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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11. 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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14. Preparing a Dispersion
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.
Wetting of the powder this is necessary not to wet external surfaces but also for displacing air between the internal clusters.
Dispersing by using charged bulky surfactants e.g. sodium oleate, sodium or ammonium caseinate
Modifying the viscosity to minimise sedimentation (see Stoke’s Law)
Dry powders usually consist of aggregates and agglomerates which need to be dispersed in the liquid to produce "individual" units which may be further subdivided into smaller particles.
This requires understanding of various phenomena such as powder wetting, dispersion of aggregates and agglomerates and comminution of the primary particles into smaller units. HOW?
Once a powder is dispersed into a liquid, it is essential to prevent aggregation of the particles and their sedimentation.
Powder wetting, dispersion and subsequent stabilization requires in most cases the use of a dispersing agent, usually a surfactant, a polymer or polyelectrolyte.
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15. 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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16. END OF LECTURE 1 OF 2
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17. Types of Emulsions Macroemulsion Nanoemulsion Microemulsion
Multiple emulsion
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18. Nanoemulsion and Microemulsion
Nanoemulsions
cover the size range of 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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19. Methods of Preparation
Nanoemulsions are easily formulated using high-pressure 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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21. 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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22. 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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23. 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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24. 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, Shinchon-dong, Seodaemoon-gu, Seoul, , 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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25. 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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26. 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 m in mean diameter, spherical in shape, and had a porous structure.
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27. Multiple Emulsion for Pharmaceuticals Examples
Sandostatin LARTM Depot – Novartis (hypothalamic hormones analogue)
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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28. Multiple emulsion Pharmaceutical Problems
Rapid release during the first day typically accounts for 10-80% of the total drug loading. This ‘initial burst’ poses a toxicity threat and is a major hurdle for the development of microspheres.
Very slow (close to zero) release period after the initial burst period. This can last for weeks and is referred to as the ’lag-time’. During this induction period, the patient is not effectively treated due to lack of drug release.
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29. 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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30. 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.
Results from a suspension of fine particles that obscures light rays - requires many days for sedimentation because of the small particle size.
In industries: 1. light-interference method is classified as nephelometric. Unit of measurement is nephelometric turbidity unit, NTU. 2. When formazin is used to prepare turbidity standards for comparator tube determinations, the unit is formazin turbidity unit, FTU.
Turbidity, t, is the fractional decrease in intensity of the incident light, which passes through 1 cm of solution.
It is expressed as the intensity of light scattered in all direction (Is) divided by the intensity of the incident light, I.
t = Is / I
At a given concentration of a dispersed phase, turbidity is proportional to the molecular weight of the lyophilic colloid:
  M
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31. 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.
Brownian motion – arises from bombardment of dispersed particles by molecules of dispersion medium.
Diffusion – particles diffuse spontaneously from region of high to low concentration, according to Fick’s law the amount of substance dq diffusing in time dt across a plane with surface area S:
dq = -DS(dc/dx)dt
where D is the diffusion coefficient and dc/dx is the concentration gradient.
Osmotic pressure: allows the calculation of molecular weight of colloid
Sedimentation: as given by Stoke’s law
Viscosity – resistance to flow under applied stress Brownian motion – arises from bombardment of dispersed particles by molecules of dispersion medium.
Viscosity – resistance to flow under applied stress
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32. References
PC Hiemenz & Raj Rajagopalan, Principles of Colloid and Surface Chemistry, Marcel Dekker, New York (1997)
HA Lieberman, MM Rieger & GS Banker, Pharmaceutical Dosage Forms: Disperse Systems Volume 1, Marcel Dekker, New York (1996)
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)
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