Post on 22-Nov-2014
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Colloid systems(Coarse Dispersions)
Dr Woei Ping Cheng
Senior lecturer of pharmaceutics
w.p.cheng3@herts.ac.uk
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Colloid systemsLearning Objectives
Learn how to define a colloidal systemLearn how colloids differ from solutionsUnderstand how to differentiate the numerous
types of colloidal systemsLearn to identify the key features of a colloidal
systemUnderstand the stability of colloidsLearn how colloids are used practically
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Colloid systems
OutlineLearning objectivesIntroductionTypes of colloids Properties of colloidsStability of colloidsDLVO theoryThe pharmaceutical application of colloidsSummary
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Solvent molecules
Colloid particle
Colloid systems
Solutions vs colloids
solventsolute
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Colloid systems
What is a colloid?
Solution
Suspension
Colloid
Dispersed system-continuous phase-dispersed particles (1nm to 1um)
Dispersed system-continuous phase-dispersed particles (usually > than1um)
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Colloid systems
IntroductionWhat is a colloid?
A colloid or colloidal dispersion, is a two-phase system of matter; a type of mixture intermediate between homogeneous mixtures and heterogeneous mixtures (size 1nm - 1m, although upper limit can be extended)
In a phase colloid, small droplets or particles of one component, the disperse phase, are dispersed in continuous phase. In a molecular colloid, macromolecules are dispersed in a continuous phase (or dispersion medium)
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Colloid systems
IntroductionColloids were discovered and
described by chemist Thomas Graham, in 1860, as substances that would go through a semi-permeable membrane in a process called dialysis, which has the purpose to separate those solutions that can’t be filtered.
Types of Colloids
Dispersed phase
Dispersion medium
Name Examples
solid liquid sols toothpaste
liquid liquid emulsion Milk, mayonnaise
gas liquid foams Soap foams
Solid/liquid gas aerosols Smoke, mist, fog
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Colloid systems
1. Sols: Solids dispersed in a liquid 4 main types
Lyophilic (Solvent-loving) Lyophobic Colloids (Solvent-hating) Association Gels
2. Emulsions (liquid in a liquid)
3. Foams (gas in a liquid)
4. Aerosols (liquid in a gas)
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Colloid systems
1. Sols: Solids dispersed in a liquidLyophilic Colloids
Classified as hydrophilic sols in aqueous media
Spontaneous formationE.g. large organic molecules (acacia,
gelatin, albumin, polymers etc) dispersed in water
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Colloid systemsSols: Lyophilic colloids
Albumin in waternm sizeInvisibleCharge stabilised, pH dependency, Isoelectric point
Preparation techniquesIn aqueous media; the molecules become hydrated by interacting with the waterRubber & Polystyrene are solvated by non-aqueous
organic solvents to form lyophilic solsPharmaceutical uses; suspending and emulsifying agents,
binders etc
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Colloid systems
Sols: Solids dispersed in a liquidLyophobic Colloids
Classified as hydrophobic in aqueous mediaE.g. inorganic particles dispersed in water, Au,
Ag, S etcThermodynamically unstableThese are insoluble and have little or no
attraction for the dispersion mediumReversible or irreversible aggregationPreparation techniques
• Dispersion, Milling, ultrasonics, electric arc (large to colloid)
• Condensation from solution e.g. colloidal hydrated ferric oxide
Look up preparation techniques
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Colloid systems
Sols: Solids dispersed in a liquidLyophobic and lyophilic colloids
Previously discussed
Association colloids In effect - Micelle forming compounds
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Colloid systemsSols: comparison
Lyophobic Lyophilic
Inorganic molecules or particles, or insoluble!
Large organic molecule in colloidal size range
Little or no interaction between particles and dispersion medium
Solvated by medium (H2O – this is hydrated)
Do not disperse spontaneously special procedures needed
Disperse spontaneously
No effect on viscosity unsolvated
Increase viscosity forming gels at higher concentrations
Electrolytes: low concentrations may stabilize Higher concentrations cause instability
Electrolytes: generally stable but “salted out” by very high concentrations due to desolvation
Copyright of Prof. M. B. Brown 2007 15
Colloid systems
GelsCan be formed from both lyophilic or lyophobic solsOnly a small concentration of the colloid is required
to form this network (typically 1%) If the system is gel rich – Jelly If the water is removed from a jelly – Xerogel (e.g.
sheet gelatin)
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Colloid systems
Sols: Gels
Solid particles will arrange themselves into a 3D structure within the liquid solvent, giving the solution a rigid, definite shape as in a jelly.
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Colloid systems
2. Emulsions: Liquids dispersed in a liquidAn emulsion is a mixture of two
immiscible (unblendable) substances
Oil in waterWater in oilMultiple emulsions, w/o/w or o/w/oMicroemulsions (spontaneous
formation)Homogeneity is key
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Colloid systems
3. Foams: Gases dispersed in a liquidFormed by trapping many
gas bubbles in a liquid or solid
Also produced as an often unwanted by-product in the manufacture of various substances
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Colloid systems
4. Aerosols: solid/liquid in a gasCan be solid or a liquid that
will dry to form a solidProvides propulsionGas can be a liquid under
pressure
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Colloids systems
Why do pharmacists need to understand the major principles of colloid science?
Formulation tool for drug deliveryHydrophobic drugs in aqueous solventsCosmetically acceptable topical productsAerosols for inhalationManufactureFormulation must deliver a safe reproducible dose
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Colloid systems
What can go wrong with a formulation once manufactured??
Contamination (e.g. microbial)Chemical instability
ImpuritiesToxic adducts
Physical instabilityPoor dosing reproducibility
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Colloid systems
Greater understanding of colloidal properties required Kinetic properties
Motion of the particles with respect to the dispersion medium• Brownian motion• Diffusion• Sedimentation• Osmotic pressure• Viscosity
Adsorption Dialysis Size/Shape Electrical properties Together influence movement thus, physical stability
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Colloid systemsProperties of colloids
Light scattering-Tyndall effectthe light beam is not visible as it
passes through a true solution (left), but it is readily visible as it passes through colloidal iron (III) oxide in water.
can be measured to estimate particle size,shape and interactions
most colloids show low turbidities so instead of measuring transmitted light (which may only differ marginally from incident beam) scattered light is measured at 90o.
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Colloid systemsProperties of colloids
Brownian motionColloidal particles subject to
random collisions with the molecules of the continuous phase
each particle pursues an irregular and complicated random path
Named after Robert Brown in 1827 after his observation of pollen grains suspended in water
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Colloid systems
Properties of colloids Diffusion
As a result of Brownian motion colloidal particles diffuse from a region of high to low concentration
Rate is based on Fick’s first law:
dx
dCDA
dt
dm
dm/dt = mass of substance diffusing over timeA = areaD = diffusion coefficientdC/dx = concentration gradient
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Colloid systemsProperties of colloids
Diffusion coefficient (D)
R – Universal gas constantT – Temperature- Viscositya – particle radiusN – Avogadro numberaN
RTD
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Diffusion coefficient can be obtained experimentally by refractive index or dynamic light scattering
Ultimately can be used to calculate molecular weight of a spherical particle
Copyright of Prof. M. B. Brown 2007 27
Colloid systemsProperties of colloids
Osmotic pressureIf a solution and a solvent are separated by a semi-
permeable membrane the tendency to equalize chemical potentials (hence concentrations) on either side of the membrane results in a net diffusion of solvent across the membrane.
The pressure necessary to balance this flow is known as osmotic pressure
Where C is the concentration of solution, M is the molecular weight of the solute and B is a constant
BCMRTC //
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Colloid systemsProperties of colloids
Osmotic pressure
A plot of /C versus C is linear, with the value of the intercept as C=0 giving RT/M enabling the molecular weight of the colloid to be calculated
A useful technique for the study of colloidal particlesMore sensitive than some of the other methods mentionedHowever limited to molecular weight range of 104-106
Potential source of error is the Donnan Membrane Effect where the diffusion of small ions is affected by the presence of macromolecules which block the membrane
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Colloid systems
Properties of colloids Sedimentation
Particle falling under the forces of gravity according to Stokes law
Only applies to >0.5 mStronger force than gravity is needed for colloidal particles to sediment
9/)(2 2 gava – particle radius
- density
- vehicle density
- viscosity
g – gravity
- velocity
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Colloid systems
Properties of colloidsViscosity /Thixotropy
Many gels and colloids are thixotropic materials Thixotropy is the property of some non-newtonian
pseudoplastic fluids to show a time-dependent change in viscosity; the longer the fluid undergoes shear, the lower its viscosity.
Exhibiting a stable form at rest Becoming fluid when agitated Shear breaks the weak bonds (e.g. shaking)E.g. bentonite in calamine lotion, clays in earthquakes, tomato ketchup
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Colloid systems
Properties of colloidsAdsorption
A chemical is associated to the surface of a second agent
Often reversibleConformational changeManipulate
physicochemical properties
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Colloid systems
Properties of colloidsDialysis
When a colloids are separated/purified from micromolecular impurities
Can be hastened by stirring or renewing the outer liquid
• Ultrafiltration-applying pressure to force small molecules across membrane
• Electrodialysis –applying electrical potential to increase movement of ionic molecules
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Colloid systems
Colloidal sols Vs Solutions
Colloidal sol Solutions
Light Scattering
Dialysis
Adsorption
Affected by electrical charge
Light passes through
No separation
Adsorption
Not affected by electrical charge
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Colloid systems
Properties of colloids Size
Particle size reduction results in an increase in the specific surface (e.g. surface area per unit weight)
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Colloid systems
Properties of colloidsShape
Many types of colloids are sphericalSeveral measurement techniques assume a
sphereHowever, some are not sphericalSmall deviations – ellipsoidal modelsLarge deviations – clay suspensions (plates)
- polymers in solution (coil)
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Colloid systems
Properties of colloids Electrical properties
Most surfaces acquire charge and there are various charging mechanisms
Ion dissolution• Ionic substances can acquire surface charge by
unequal dissolution of the oppositely charged ions of which they are composed
• AgI Ag+ + I-
• Particles of AgI with excess I- will be negatively charged and vice versa
• Ag+ and I- are termed potential determining ions
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Colloid systems
Properties of colloids Electrical properties
Ionization• Charge is controlled by the ionization of surface groupings
• e.g. polystyrene latex where the carboxylic acid group is ionized (COO-)to give negatively charged particles
• e.g. amino acids and proteins- COO- -NH3+,the net charge
depending upon the pH
Ion adsorption • Net surface charge by unequal adsorption of oppositely
charged ions
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Colloid systems
Properties of colloids Electrical properties
Electrical double layer• For a solid charged surface in contact with an aqueous solution
containing –ve and +ve ions• Surface charge influences the distribution of ions in the aqueous
medium• Oppositely charged ions (counter ions) are attracted to the surface• Ions of like charge (co-ions) are repelled from the surface• However distribution of ions is also affected by thermal
agitation/movement which tends to redisperse the ions in solution• Results in the formation of an electrical double layer, comprising
a charged surface and a neutralising excess of counter ions over co-ions (must be neutral) distributed in the aqueous media
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Electrical double layer continued • Guoy, Chapman and Stern theory• Double layer divided into two parts• inner part = adsorbed ions• diffuse part =where counter ions are distributed
by electrical forces and random thermal motion• Two parts are separated by the ‘stern plane’ at
about a hydrated ion radius from the surface• Counter ions may be held at the surface by
electrostatic attraction and centre of these hydrated ions forms the Stern plane
• Surface of shear = The edge of the solvating layer held to the surface. It
represents the boundary of relative movement between the solid and the liquid.
• Zeta potential () = An estimate of surface potential. It is the potential at the surface of shear, less than Stern potential ().
• 1/ = The distance of exponential decay of potential to zero with distance from the Stern plane
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Colloid systems
Properties of colloids Question – What may happen in a colloid
system if weDecrease particle size?Increase temperature?Decrease viscosity?Increase the electrical charge?
We can influence the colloidal interactions
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Colloid systems
Physical StabilityVery important for lyophobic colloidal systemsFrequent encounters between particles occur within
colloidal dispersions as a result of Brownian motionMay lead to coagulation or flocculation, or neither
(stable colloidal system)Outcome depends on the forces of interaction
Aggregation = general term refers to collection of particles in groups
Coagulation = closely aggregated and difficult to redisperse
Flocculation = temporary contact, aggregates have an open structure with particles a small distance apart
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Colloid systems
Physical StabilityDLVO theory of colloid stability (Derjaguin,
Landau, Verwey, Overbeek)Considered the interaction between 2 colloidal
particles in a lyophobic systemAssumed that the only interactions involved are
electrical repulsion VR and van der Waals attraction VA
These are additive
RAT VVV Total potential energyof interaction
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Colloid systemsDLVO theory of colloid stability
Repulsive forces between particles• Arises because of the osmotic effect produced by the
increase in number of charged species overlapping the diffuse part of the electrical double layer
• Has an exponential function of the distance between the 2 particles and has a range of about the thickness of the double layer
Attractive forces between particles• Arises from van der Waals universal forces of attraction
(dispersion forces), the major contribution is electromagnetic attractions
• Dispersion forces are additive
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DLVO theory of colloid stability
•Attraction predominates at small distances (deep primary minimum) -Coagulation: The irreversible aggregation of distinct particles into large particles
•At larger particle distances a secondary minimum occurs as the loss in repulsive energy is more rapid than the attractive energy -The flocculated material can often be redispersed by agitation because the well is so shallow.
•At intermediate distances, double layer repulsion may predominate giving a primary maximum to the curve -stable system
VT
Primary minimum
Net energy
Distance (d)Between particles
Secondary minimum
Primary maximum
d
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Colloid systems
DLVO theory of colloid stabilityIn reality
Stability of the colloid particles depends upon • the thermal energy of the system kBT,• zeta potential, • electrolyte concentration,• Ionic charge and size • surface active agents• Other parameters
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DLVO theory of colloid stability
primary maximum > thermal energy, kBT of the particles = stable system
Secondary minimum > kBT = particles will form a loose assembly which can be readily redispersed, i.e. flocculation occurs
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DLVO theory of colloid stability
simplified systems Are these colloids stable?
1. A2. B3. C4. D
AB
C
D
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Colloid systems
Physical StabilityColloids must be physically stable to ensure
consistent dosingPractically how do we stabilise lyophobic
colloids? Influence movementInfluence particle interaction
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Colloid systems
Pharmaceutical colloidsDiclofenac Sodium
Solaraze®A topical treatment for a
common dermatological condition, actinic keratosis
hyaluronic acid gel technology maximises the concentration of the active drug (diclofenac) in the upper layers of the skin
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Colloid systems
Pharmaceutical colloidsHuman Recombinant
DNaseDornase alfa®Formulated as a
lyophilic colloidalNebulisedMucolytic
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Colloid systems
Pharmaceutical colloidsCiclosporine
NEORAL® – ImmunosuppressantsOral capsuleMicroemulsion
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Colloid systems
Pharmaceutical colloidsGold
Mesogold® Colloidal gold is supposed
to increase mental acuity
and the ability to concentrate Lyophobic sol
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Colloid systems
Summary – ColloidsDefinition of colloidsUnique properties of a colloid (vs solution)Types of colloidsPhysical stability of colloids – lyophobic solsDVLO theoryGelsPharmaceutical colloids