emulsion Flashcards
what is an emulsion
a system consisting of two immiscible liquid phases, one of which is dispersed as fine globules thoroughout the other
what is an emulsion stabilised by
addition of an emulsifying agent
what is the liquid that is subdivided into globules called?
disperse phase/ internal phase
what is the liquid in which the globules are dispersed in called?
continuous phase/ external phase
how may emulsions be administered
- topically
- orally
- parenterally
types of emulsion
- simple emulsion (o/w, w/o)
- multiple emulsions (o/w/o; w/o/w)
- micellar emulsions
- microemulsions
microemulsions
containing extremely small globules (10-75nm), dispersed in continuous phase, appears transparent to naked eye
micellar emulsion
consist of relatively high concentration of surfactant and a small proportion of disperse phase which is solubilised by the surfactant
- surfactant exist as micelles (5-20nm) which are extremely small (hence seems transparent to naked eye)
two types of micellar emulsions
- oil in water: oil is found in non-polar interior of the micelles which are present in aq continuous phase
- reverse micelle emulsion: consist of water which is found in the polar interior of the micelles which are present in an oily continuous phase
testing o/w emulsions
- color: usually white
- feel on skin: initially non-greasy
- filter paper wetting: diffuses rapidly
- filter paper impregnated with cobalt chloride: blue to pink
- fluorescence: dot pattern under uv light
- conductivity: conducted electricity
- dye test: globules colored by oil-soluble dye while continuous phase by water-soluble dye
- dilution: miscible with water
testing w/o emulsion
- color: assume color of oil
- feel on skin: greasy
- filter paper wetting: diffuses slowly
- filter paper impregnated with cobalt chloride: remains blue
- fluorescence: fluoresces throughout
- conductivity: poor conductor
- dye test: globules colored by water-soluble dye while continuous phase by oil-soluble dye
- dilution: miscible with oil
basic component of emulsion
oil, water, surfactant
oil phase
- choice determined by ultimate use of emulsion
- affect the performance: consistency, feel/tactile, stability, drug solubility
emulsifying agent divided into three broad classes
- surfactant
- hydrophilic colloids
- finely divided solids
factors affecting selection of emulsifying agents
- type of emulsion (o/w or w/o)
2 compatibility - toxicity
- cost
different types of emulsifying agents
- tweens and spans
- sodium lauryl sulphate
- cetostearyl alcohol
- sodium alginate
- sodium carboxymethyl cellulose
surfactants
have hydrophilic group and lipophilic group in their molecular structure
- amphipathic in nature to cause molecules to become attached to interfaecs, lowering interfacial tension
four major groups of surfactants
- anionic
- cationic
- amphoteric
- nonionic
anionic surfactants
- generally employed for external preparations
- incompatible with cationic compounds, low pH, high concentration of electrolytes
- effectiveness enhanced by nonionic surfactants
different types of anionic surfactants
- soaps of monovalent bases
- soaps of polyvalent bases
- amine soaps
- sulphated and sulphonated fatty acids and alcohols
- quillaia saponins
soaps of monovalent
- eg. sodium/ potassium/ ammonium stearate
- o/w
- presence of polyvalent cations will cause phase inversion
- sodium and potassium soaps have high pH and unsuitable for emulsions where high pH cannot be tolerated
soaps of polyvalent
- eg. calcium/ zinc oleate
- w/o
- presence of monovalent cations will cause phase inversion
soaps of amines
- eg. triethanolamine
- o/w
- suitable for o/w emulsions where high pH cannot be tolerated
sulphated and sulphonated fatty acids and alcohols
- eg. sodium lauryl/cetyl sulphate
- o/w
- generally mroe effective than other types but strongly alkaline
- SLS + CSA = emulsifying wax
quillaia saponins
- o/w of low viscosity
- glycosides form quillaja saponaria
- can be employed for oral preparation
cationic surfactants
- possess emulsifying and antiseptic properties
- incompatible with anionic compounds
- promote o/w emulsion
example of cationic surfactants
quaternary ammonium compounds
- cetrimide
- cetyl pyridinium chloride
- benzalkonium chloride
amphoteric surfactant
- cationic at low pH and anionic at high pH
- not widely used cause expensive
- eg lecithin for IV fat emulsion
nonionic surfactants
- low toxicity and irritancy
- less sensitive to pH changes and addition of electrolytes
- for external as well as internal preparation
types of nonionic surfactants
- sorbitan esters and polyoxyethylene sorbitan esters
- glycol and glycerol esters
- fatty acid polyglycol esters
- fatty alcohol polyglycol esters (macrogrol ethers)
- higher fatty alcohols
sorbitan esters and polyoxyethylene sorbitan esters
sorbitan esters (Span), polyoxyethylene sorbitan esters (Tween)
- blends of sorbitan ester and polyoxyethylene sorbitan ester are usually employed
- depending on the HLB of the blend, it may promote the formulation of o/w and w/o emulsion
glycol and glycerol esters
eg. glyceryl monostearate
- promote formation of o/w emulsions
- effectiveness enhances by soap of monovalent bases and amine soaps
fatty acid polyglycol esters
eg. POE 40 stearate
- promote formation of o/w emulsions
- effectiveness enhanced by stearyl alcohol
fatty alcohol polyglycol ethers
eg. cetomacrogol 1000
- blends to hydrophilic and lipophilic members are usually employed
- depending on HLB of blend (o/w or w/o)
- cetomacrogol 1000 + cetostearyl alcohol = cetomacrogol emulsifying wax
higher fatty alcohols
eg. cetostearyl alcohol
- auxilliary emulsifying agents
hydrophilic collioids
more useful as auxiliary emulsifying agents and as thickening agents; generally favour the formation of o/w emulsions
types of hydrophilic colloids
- natural and synthetic clays (bentonite)
- natural and synthetic gums (acacia, tragacanth, sodium alginate, carrageenan, locust bean, guar, xanthan, sodium CMC, methyl cellulose)
- proteins (eg. gelatins, soluble casein)
natural and synthetic clays
- bentonite derived from montmorillonite from typical smectite clay
- swells in the presence of water but raises the viscosity of medium only at pH6 or higher
natural and synthetic gums
- polysaccharides
- most commonly used
- exhibit incompatibility with certain cations or pH
- sodium alginate and sodium CMC are incompatible with acids
- methyl cellulose is less soluble in hot water
proteins
- less commonly used
- gelatin prepared by partial hydrolysis of collagen
finely divided solids
- not major interest to the formulator because limited utility as primary emulsifying agents
- solids of mineral origin should be sterilised before used because they may contain tetanus spore
types of finely divided solids
- non-polar solids: favour the formation of w/o emulsions (eg. carbon, glyceryl tristearate)
- polar inorganic solids: favor formation of o/w emulsions (eg. heavy metal OH, non swelling clays)
Theory of emulsification
- When oil and water are mixed together, droplets of varying sizes are produced.
- A tension exists at the droplet interface because the two immiscible phases
tend to have different attractive forces for a molecule at the interface - Such a system is thermodynamically unstable
Formation of a rigid interfacial film
- chlolesterol + sodium cetyl sulphate: closely pakced condensed complex (stable)
- oleyl alcohol + sodium cetyl sulphate: loosely packed condense complex (poor emulsion)
- cetyl alcohol + sodium oleate: fairly closely packed but no complex formation (fairly poor emulsion)
formation of an electric double layer
- applied for ionic surfactants
- electric double layer serves as an electrical barrier to approach droplets
Increase viscosity of the continuous
phase
- Gums and waxes are commonly used to increase the
viscosity of water and oil respectively. - A more viscous continuous phase generally produces a
more stable emulsion.
Bancroft’s Theory
- The adsorption of surfactants at the oil/water
interface gives rise to an interfacial film. - This film experiences two interfacial tensions, one
between the film and the aqueous phase and the
other between the film and the oil phase. - The film will curve in the direction of the greater
interfacial tension. Thus, the disperse phase is on
the side of the film with the higher interfacial
tension.
Oriented wedge theory
- Harkin attempted to explain the type of emulsion
formed by soaps, such as sodium oleate (soap of
monovalent base) and magnesium oleate (soap of
divalent base). - Surfactant molecules (e.g. soaps) will orientate at
the oil/water interface such that a tightly packed
film is formed. - The relative location of the polar heads of the soap
molecules will determine the type of emulsion
produced.
Theory based on angle of contact
- This applies to emulsifying agents which are finely
divided solids, with the following properties:
> Insoluble in both aqueous and oily phases.
> Preferentially wetted by one of the phases.
> Able to form a thin interfacial film.
> Of colloidal size. - Such solid particles are attracted to the interface
between the two immiscible liquids. - The angle of contact formed by the solid particle at the interface determines the type of emulsion
produced.
what is HLB and how to calculate
This ratio of these two groups affects the water or
oil solubility of the surfactant aka the hydrophile-lipophile balance.
HLB = weight of hydrophilic grp / MR x 20
HLB ranges with applications
4-6: w/o emulsifying 7-9: wetting agents 8-18: o/w emulsifying agents 13-15: detergents 10-18: solubilising agents
theories of how emulsion works
- Bancroft Theory
- Oriented wedge theory
- Theory based on angle of contact
techniques of emulsification
- agent in water method
2, agent in oil method - Nascent soap method
- Alternate addition method
agent in water method
- emulsifying agent is incorporated in water and the oil is then added with agitation, producing o/w emulsion directly
- for w/o, addition of oil is continued until phase inversion occurs
agent in oil method
- emulsfying agent is incorporated in oil, which is then added to water with vigorous agitation forming o/w emulsion
- for w/o emulsion, addition of oil phase continues until phase inversion occurs
Nascent soap method
- suitable for emulsions with soap as the emulsifying agent.
- The fatty acid is dissolved in the oil and the base
in the water. - The soap is formed in situ as the oil and aqueous phases are brought into contact during mixing and an emulsion is subsequently produced.
- Depending on the type of soap, o/w or w/o
emulsions are produced.
Alternate addition method
- This method is particularly suitable for vegetable
oils. - The water and oil are added alternately in small
amounts to the emulsifying agent.
Types of emulsifying machines
• Simple stirring
• Colloid milling
• Vibration and ultrasonification
Further homogenization to improve stability
Stability of emulsions
there is no coalescence of disperse phase that ultimately leads to separation of the oil and aqueous phases
signs of emulsion instability
creaming, flocculation, coalescence and/or cracking
creaming
Under influence of gravity, the globules tend
to rise or sediment depending on the differences
in specific gravities between the phases.
This results in concentration of the disperse phase
at the top or bottom of the system which can be
readily redispersed on shaking. (reversible)
stokes law
- applies to an isolated sphere in an infinitely large
mass of liquid. - The hindrance to motion depends on the concentration
of the droplets of the disperse phase and this in turn
depends on the volume fraction of the disperse phase
improve stability of emulsion by
- increasing radius of droplets !!
- decrease viscosity of continuous phase !!
- increase difference in densities of disperse phase and continuous phase
flocculation
- reversible aggregation of droplets of the
disperse phase in the form of three-dimensional clusters. - The droplets do not lose their identity entirely as the
mechanical or electrical barrier surrounding the droplet is
sufficient to prevent droplet coalescence.
coalescence
- droplets join to form larger drop
- irreversible, leading to decrease in number of droplets and finally cracking
cracking
- complete breakdown of emulsion with coalescence of droplets and separation of two phases into two layers
- may be due to chemical, physical and biological effects
examples of substances that are incompatible with emulsifying agent ad cause cracking
- strong acids/alkali metal soap
- anionic compounds + cationionic surfactants
- cationic compounds + anionic surfactants
- high concentration of electrolytes + soaps
- alcohol + gums
assessment of emulsion stability
- centrifugation
- agitation
- freeze-thaw cycle
- heating-cooling cycle
but if stress is excessive may lead to abnormal processes
Determination of degree of separation
- The ratio of the volume of separated phase and the total
volume of emulsion is determined. - A stable emulsion should not show any
Size analysis of globules
- The mean size of the globules with time is determined by
microscopic examination, electronic particle counting
method (e.g. Coulter Counter) or laser diffraction
technique. - Emulsions which are less stable show greater increase in
the mean globule size with time.
This is attributed to coalescence of globules which is a
form of emulsion instability
Determination of electrophoretic property
- The emulsion conductivity is dependent on the
degree of dispersion. - Reduction in conductivity of o/w emulsions
indicates oil droplet aggregation and instability. - Conductivity of w/o emulsion indicates water
droplet aggregation and instability. - Measurements are made, with the aid of platinum
electrodes, on emulsions stored for short periods
of time.
Determination of viscosity changes
- The emulsion viscosity is affected by the globule
size and number. - Hence, changes in emulsion viscosity can be used
to indicate emulsion stability. - This is measured using viscometers.
