Colloids 2010 Lectures Studynet (1)

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Colloid systems(Coarse Dispersions)

Dr Woei Ping Cheng

Senior lecturer of pharmaceutics

[email protected]

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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

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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