Disperse systems directed study Flashcards
Globule size
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
Emulsifier interfacial film properties
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
Electrostatic repulsion
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
Phase volume ratio
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
Density difference between phases
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
Viscosity of continuous phase
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
Increased temperature
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
Decreased temperature
Lower temperatures are generally better for emulsion stability, but freezing can:
Precipitate emulsifier
Form water crystals which can damage emulsifier film
Surface active agents
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
Ionic SAA emulsifiers
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
Cationic SAA emulsifiers
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
Anionic SAA emulsifiers
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
Amphoteric SAA emulsifiers
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)
Non-ionic SAA emulsifiers e.g. span, tween, glyceryl esters
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
Hydrophilic colloid emulsifiers
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
Natural hydrophilic colloids- vegetable
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
Natural hydrophilic colloids- animal
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
Modified hydrophilic colloids- semi-synthetic e.g. methylcellulose, carboxymethylcellulose
Not natural products so decreased batch-batch variation and microbial growth less likely
Stronger emulsifiers than natural products
Non-toxic
Modified hydrophilic colloids- synthetic e.g. carbopols
Generally o/w emulsifiers Stronger emulsifiers than semi-synthetics or natural products Do not support microbial growth Non-toxic Expensive
Finely divided solid emulsifiers
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
Other emulsifiers
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
Excipients- general notes
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
Polysaccharide viscosity modifiers
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
Water soluble celluloses
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)
Hydrated silicates
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
Other commonly used viscosity modifiers
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
