Disperse systems directed study

Question 1

Globule size

Answer 1

Rate if creaming is increased for larger globules
Globule size is dictated by method of manufacture and emulsifier properties
Polydispersity (a mixture of sizes) is undesirable because small globules can fit between larger ones, leading to increased cohesion, decreased adhesion and phase separation

Question 2

Emulsifier interfacial film properties

Answer 2

Emulsifiers help keep oil and water phases mixed and usually form a film around the dispersed phase globules
This is probably the most important method in stabilising emulsions
The film should form rapidly during emulsification and be tough and elastic

Question 3

Electrostatic repulsion

Answer 3

Charges provided by the emulsifier at the surface of the globules creates electrostatic repulsion between globules
Increased zeta potential leads to more stable emulsions
The addition of charges to the system, e.g. by adding electrolytes or by changing pH can neutralise the charge, and reduce repulsion and therefore stability

Question 4

Phase volume ratio

Answer 4

The relevant amount of oil and water is important- the higher the concentration of dispersed phase, the more likely that globules will meet and possibly merge, but the increased concentration slows down movement of globules
A ratio of ~50:50 is usually the most stable
Above ~70% dispersed phase, the emulsifier cannot maintain a stable emulsion
Below ~20%, creaming occurs readily

Question 5

Density difference between phases

Answer 5

If the densities of the two phases were identical, creaming would not occur
Greater density differences lead to increased creaming
Not used to stabilise emulsions because density varies with temperature and could affect each component of the emulsion to a different extent

Question 6

Viscosity of continuous phase

Answer 6

Viscosity alone cannot make an emulsion stable
Increased viscosity decreases globule movement so can decrease the rate of coalescence
Affected by:
PVR- higher conc of dispersed phase can lead to pseudoplasticity (which is good)
Globule size distribution- decreased polydispersity leads to increased viscosity

Question 7

Increased temperature

Answer 7

At increased temperatures:
Decreased viscosity leads to increased creaming
Increased kinetic energy leads to increased collisions leads to increased phase separation
Increased kinetic energy leads to increased motion of emulsifiers leading to more fluid interfacial film
Increased microbial growth
Coagulate some macromolecular emulsifiers

Question 8

Decreased temperature

Answer 8

Lower temperatures are generally better for emulsion stability, but freezing can:
Precipitate emulsifier
Form water crystals which can damage emulsifier film

Question 9

Surface active agents

Answer 9

Can be divided into ionic and non-ionic categories; each have different characteristics and uses
SAAs adsorb at interface, creating monomolecular film and decreasing interfacial tension
Can cause haemolysis of erythrocytes so injectables must be made isotonic

Question 10

Ionic SAA emulsifiers

Answer 10

Mostly for o/w emulsions
Can be quite toxic, so are mostly used as disinfectants/ preservatives rather than emulsifiers
If used as emulsifier, are for external use only due to toxicity
Used in antiseptic creams as they have both emulsifying and antimicrobial actions
Cheap, but form quite weak films so usually used in conjunction with non-ionic emulsifier

Question 11

Cationic SAA emulsifiers

Answer 11

e.g. benzalkonium chloride, quarternary ammonium compounds, cetrimide
Ionise in water into a large cation and a small anion
Incompatible with anions and high pHs

Question 12

Anionic SAA emulsifiers

Answer 12

e.g. alkali soaps (sodium/ potassium/ calcium oleate), amine soaps (triethanolamine stearate/ oleate), alkyl sulphates (sodium lauryl sulphate, sodium docusate)
Ionise to a large anion and a small cation
Incompatible with cations and low pHs

Question 13

Amphoteric SAA emulsifiers

Answer 13

Can possess both positively and negatively charges groups, depending on pH of system
Therefore cationic at low pH and anionic at high pH
Not widely used, except lethicin (egg yolk phospholipid)

Question 14

Non-ionic SAA emulsifiers e.g. span, tween, glyceryl esters

Answer 14

Do not ionise in aqueous solution, so charges are not involved in their actions
Form bulky interfacial film which also allows steric repulsion
Widely used, often in combination to make strong complex film
Low toxicity/ irritancy, so good for oral/ injectables
Less sensitive to electrolytes/pH variation, so less chance of incompatibilities
More expensive than ionics
Decrease efficacy of some preservatives

Question 15

Hydrophilic colloid emulsifiers

Answer 15

Almost always used for o/w as they are hydrophilic
Form strong multimolecular films
Some have ionisable groups which enable electrostatic repulsion
Steric repulsion can occur e.g. with cellulose derivatives
Increase viscosity of the system
Inexpensive and non-toxic
Require relatively large quantities to be effective as emulsifiers
May be natural, semi-synthetic or synthetic

Question 16

Natural hydrophilic colloids- vegetable

Answer 16

Generally o/w emulsifiers e.g. acacia- strong film, low viscosity so high chance of creaming, feels sticky so internal use only
Tragacanth- used with acacia to increase viscosity
Agar, pectin, carrageenan, sodium alginate

Question 17

Natural hydrophilic colloids- animal

Answer 17

Can form w/o emulsions
May cause allergic reactions e.g. phospholipids- lethicin from egg yolk, sterols- cholesterol, lanolin, wool alcohol, beeswax, proteins- gelatin, casein

Question 18

Modified hydrophilic colloids- semi-synthetic e.g. methylcellulose, carboxymethylcellulose

Answer 18

Not natural products so decreased batch-batch variation and microbial growth less likely
Stronger emulsifiers than natural products
Non-toxic

Question 19

Modified hydrophilic colloids- synthetic e.g. carbopols

Answer 19

Generally o/w emulsifiers
Stronger emulsifiers than semi-synthetics or natural products
Do not support microbial growth
Non-toxic
Expensive

Question 20

Finely divided solid emulsifiers

Answer 20

Form a particulate film around dispersed phase
Emulsify if preferentially wetted by one phase but can still adhere to other
Particles must be sufficiently small to not be affected by gravity
May also swell and increase emulsion viscosity
Usually used for external preparations
Cannot be used for injectables as particles
Usually for o/w emulsions e.g. bentonite, veegum, hectorite
Some used for w/o e.g. carbon black and talc

Question 21

Other emulsifiers

Answer 21

Some fatty acids e.g. stearic acid, fatty alcohols e.g. stearyl or cetyl alcohol, fatty esters e.g. glycerly monostearate stabilize emulsions by increasing the viscosity of the emulsion
Viscosity alone cannot maintain emulsion stability so always used in combination with other emulsifiers

Question 22

Excipients- general notes

Answer 22

Many excipients have more than one use- the type of product being made and the concentration of excipient should help you deduce why the excipient is included
Natural products are usually cheaper than synthetic or semi-synthetic versions
Natural products tend to suffer from batch-batch variation more than synthetics or semi-synthetics
Natural products are more of a risk for spore and/or microbial contamination

Question 23

Polysaccharide viscosity modifiers

Answer 23

e.g. trgacanth, alginates, acacia gum, xanthan gum, starch
Form viscous, thixotropic, pseudoplastic preparations
Can be used internally or externally
Quite narrow pH stability ranges
Many are natural products so usually use din short shelf-life products
Acacia and starch don’t give very viscous systems alone so are often use din combination with tragacanth

Question 24

Water soluble celluloses

Answer 24

e.g. sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, microcrystalline cellulose
Semisynthetic polysaccharides with varyiong chain lengths- longer chains cause increased viscosity
Stable over wide pH ranges
Some are non-ionic so suitable for use with ionic additives (other ionics might interact)

Question 25

Hydrated silicates

Answer 25

e.g. bentonite., hectorite, magnesium aluminium silicate
Many are clays mined from the ground so are natural products
Can be used internally and externally
Readily absorb up to 12 times their own mass of water, forming thixotropic gels

Question 26

Other commonly used viscosity modifiers

Answer 26

Carboxypolymethylene- a synthetic polymer, usually used externally, forms high viscosity product between pH 6 to 11 only
Colloidal silicon dioxide- aggregates in water to form a 3D network, can be use din non-aqueous suspensions