Emulsions Flashcards
Define emulsion
An emulsion is a disperse system where atleast one liquid is dispersed in another immiscible liquid as droplets
Is an emulsion thermodynamically stable or unstable?
It is thermodynamically unstable due to the interfacial energy associated with the huge interfacial area. All emulsions are doomed to break – it is just a matter of time
Typical droplet sizes of emulsions
0.1–100μm, though some as small as 0.01μm or as large as 1000 μm
What can emulsions be used for
oral, topical and parenteral applications
Submicron emulsions
up to 500nm, milky white emulsions. E.g. Intralipid®, Diprivan®.
Nanoemulsions
Clear or translucent emulsions, <200nm (0.2μm)
Microemulsions
Strictly speaking these are not emulsions. They are single-phase, transparent systems. They represents a intermediate state between solubilised systems and emulsions. There are different understandings on this topic
Emulsion types
Oil-in-water(o/w): • Water-in-oil(w/o) • Oil-in-water-in-oil(o/w/o) • Water-in-oil-in-water(w/o/w) • For oral use:o/w(viscosity, aqueous feel) • For external use: o/w or w/o • For oral application: o/w •For i.v. application: o/w, average diameter <1μm. No droplets > 5 μm.
which should have a
higher conductivity, o/w or w/o?
o/w
Theories of emulsification - by adding surface active agents ..
by adding surface active agents, the surface energy and interfacial energy can be reduced and stability is increased
Theories of emulsification - interfacial film strength
emulsifiers can form a stable film between the oil droplets and the dispersion medium, which stabilises emulsion
Zeta potential
– charge repulsion
Interfacial energy
E=γA
What are the 2 types of interfacial films?
monolayer and multilayer films
What are monolayer films?
Monolayer films (more important) – surface active agents, e.g. Span 80 and Tween 80 – Surface tension is usually reduced, so is interfacial energy – A mixture of emulsifiers is usually better than a single emulsifier
What are multilayer films?
hydrophilic colloids (some naturally occurring polymers), e.g. acacia gum
Are all emulsifiers surface active agents?
Not all emulsifiers are SAA.
What is a common feature of surfactants.
must have a hydrophilic section and a lipophilic (hydrophobic) section in the same molecule
What is not easily soluble in water and shows surface activity?
chain of carbons is not easily water soluble, the longer the carbon chain, the more lipophilic the molecule is.
CH3(CH2)14OH
Define HLB
Hydrophile-lipophile balance.
First designated by Griffin to indicate how hydrophilic or lipophilic an surfactant is
Low HLB is
lipophilic eg. oleic acid
High HLB is
hydrophilic eg. potassium oleate
Which phase is the external phase
The phase in which the emulsifiers have higher solubility tends to be the external phase. i.e.
– hydrophilic emulsifiers, o/w emulsions
– Hydrophobic emulsifiers, w/o emulsions
Emulsifiers with HLB 4-6
w/o emulsions
Emulsifiers with HLB 8-16
o/w emulsions
more soluble in water
Required HLB of an oil phase for producing stable emulsions
Different oils require different HLB of emulsifiers for the best stability of emulsions produced
Note: the required HLB of an oil is the HLB of the emulsifiers required by the oil to form a stable emulsion. A typical oil does not have a HLB
The HLB of a mixture of non-ionisable surfactants A and B is given by
(HLB )m =
xa (HLB )a + xb (HLB )b / xa+xb
Where xa is the quantity of surfactant A, and xb is the quantity of surfactant B, (HLB)a and (HLB)b are the HLB values of A and B, (HLB)m is the HLB of the mixture
(HLB)m = xa / xa +xb (HLB)a + xb / xa +xb (HLB)b
(HLB)m = A% x (HLB)a + B% x (HLB)b
A% + B% = 100%
How to work out A% and B% to achieve a required (HLB)m?
A% = (HLB)m − (HLB)b / (HLB)a −(HLB)b
(REMEMBER THIS)
B% = 100% - A%
Types of surfactants
• Anionicsurfactants
– Soaps, e.g. sodium stearate
– Sulfated and sulphonated compounds, e.g. sodium dodecyl sulfate
• Cationic surfactants
– Cetrimide (cetyl trimethylammonium bromide)
• Non-ionic surfactants
– Glycol and glycerol esters
– Sorbitan esters(Spanseries,Span60,Span80)
– Polysorbates (Tween series, Tween 80= polysorbate 80)
– Fatty alcohol polyglycol ethers
– Poloxamers (Pluronic Series, Pluronic F68= poloxamer 188)
• Amphoteric surfactants,e.g.lecithin
• Naturally occurring polymers, e.g. Acacia
• Semi synthetic polysaccharides, e.g. cellulose derivatives, methyl cellulose
Preparation of emulsions
- Mechanical mixing device, e.g. Silverson homogeniser
- High shear homogeniser – liquid samples passes through narrow gaps under high pressure
- Microfluidizer – split feed into twin jets and collide at supersonic speed
- Ultrasonication – for laboratory and small samples only
Why is work required in prep of emulsions
Work is required due to the increased interfacial energy
Define creaming (physical stability)
Emulsion droplets moves up to the top of the emulsion and form a droplet-rich layer (cream). When the oil layer forms on the top
– The droplets remain independent (separate)
– Redispersible
– May eventually lead to the breaking of emulsions
How to avoid creaming
- Reduction of droplet size. The creaming velocity will be reduced according to Stokes’ law. For the same formulation, use a more powerful homogenisation device generate relatively more stable emulsions
- Small particles have stronger Brownian motion,which helps the droplets remain dispersed
- Control viscosity–this is possible for oral emulsions.
- Screen for best formulations
Factors leading to flocculation (physical stability)
– Charge reduction by the addition of electrolytes (compression of diffuse layer)
– Charge neutralisation by oppositely charged ions, e.g. Ca2+ or cationic polymers (for negatively charged emulsion droplets)
– Bridge flocculation by added polymers (refer to lecture slides on colloidal dispersions)
How to avoid flocculation
- Avoid the addition of charge reducing agents and
maintain sufficient zeta potential - Steric stabilisation
What is flocculation
Flocculation is the prelude of coalescence
Define coalescence and breaking (cracking) - (physical stability)
- Coalescence – refers to the process that two or more droplets merge together to form a bigger droplet.
- Breaking – coalescence occurred substantially in an emulsion so that a free clear oil layer can be seen. This is an irreversible process (in contrast to creaming which is a reversible process
What prevents coalescence
A stable/strong interfacial film helps to prevent coalescence
How can creaming and coalescence be reversed
creaming can be reversed by shaking but coalescence is irreversible
Physical Stability – Ostwald ripening
Smaller droplets get smaller (have larger solubility) and larger droplets get larger (have smaller solubility)
Chemical aspects of emulsions
The active pharmaceutical ingredients must be compatible with the excipients in the emulsions
– Most emulsions are negatively charged, so any positively charged materials may disturb the stability of emulsions, e.g. some proteins, Ca2+
– Most electrolytes will destabilise emulsions due to • compression of the diffuse layer
• salting - out effect (on the hydrated layer of emulsifiers)
– The addition of acidic materials to emulsions stabilised by soap-type emulsifiers: destabilise the emulsion.
Preservation of emulsions
Preservatives are needed to prevent the growth of bacteria for non-sterile products
• Even for sterile products preservatives are sometimes required to minimise the impact of in- use contamination (e.g. Diprivan®)
• Preservatives exert their effect in the aqueous phase where bacteria growth occurs
Preservatives –general requirements
A wide spectrum of activity against all bacteria
• Tolerability-Non-toxic,non-irritant and free from sensitisation activities
• High aqueous solubility–preservatives work in the aqueous phase as bacteria grow there
• Stability and effectiveness over a wide range of pH and temperature. pH of some emulsions tend to drop during storage
• The preservative activity needs to be tested by appropriate microbiological tests
Other additives in emulsion formulations
Antioxidants–some oil and emulsifiers are susceptive to oxidation, e.g. lecithin. Vitamin E can be used as antioxidant.
• Flavours
• Colours
• Sweetening agents
Assessment of emulsion stability
Macroscopic examination
– Creaming–cream ratio against time – Breaking?
– Changing colour?
• Microscopic examination
- Select suitable magnification so that enough number of droplets are examined
– Examine sufficient area under the microscope and avoid selecting rare exotic objects
– Beware of alien particles (not from emulsions)
• Particle size analysis –laser diffraction, Coulter counter, single
particle optical counting etc. • Rheological (viscosity) test–
– A change in size may result in a change of viscosity
• Accelerated stability test – centrifugation, freeze-thaw cycling, temperature cycling
Formulations of some emulsions
Diazepam emulsions – Fractionated soy bean oil – Diacetylated monoglycerides – Fractionated egg phospholipids – Glycerol (anhydrous-used for stability) – Sodium hydroxide (to pH8) – Water for injections
• Diprivan® - a propofol emulsion – Glycerol – Purified egg phosphatide – Sodium hydroxide – Soya-bean oil, refined – Nitrogen – Disodium edetate – Water for injections
