Emulsions Flashcards
What is emulsion
An emulsion is a system consisting of two immiscible liquid phases, one of which is dispersed as fine globules throughout the other.
This system is stabilized by the addition of an emulsifying agent
Advantage of Emulsion
Can vary components to give varying properties (flexibility) = viscosity and greasiness
Emulsion tend to look more elegant (cosmetic)
Mask bad taste; incorporate drug into dispersed phase - further mask by adding flavor into continuous phase
Slow release: drug must partition from disperse phase to continuous phase then to cell (longer time to diffuse)
Types of emulsion
Simple emulsion
Multiple emulsion
Microemulsion (10-75nm; transparent to the naked eye)
Micellar emulsion
They consist of a relatively high concentration of surfactant and a small proportion of disperse phase which is solubilized by the surfactant.
The surfactant exists as micelles (5-20 nm) which are extremely small. Hence, these emulsions appear transparent to the naked eye.
Two types:
Oil-in-water micellar emulsion
This consists of oil which is found in the non-polar interior of the micelles which are present in an aqueous continuous phase.
Reverse micellar emulsion This consists of water which is found in the polar interior of the micelles which are present in an oily continuous phase.
why is there a need to add emulsifying agent
When oil and water are mixed and agitated droplets of varying sizes are produced. A tension exists at the interface because the 2 immiscible phase tends to have different attractive forces for a molecule at the interface.The system is thermodynamically unstable. Therefore respective droplets tend to coalesce together causing phase separation which is more stable.
Hence to prevent this we have to add an emulsifying agent.
How emulsifying agents stabilize an emusion
3 theories
1) Formation of a rigid interfacial film
A tightly packed film contributes to the stability of emulsion.
Cholesterol + Sodium cetyl sulphate
Closely packed condensed complex –> Stable emulsion
Oleyl alcohol + Sodium cetyl sulphate
Loosely packed condensed complex –> Poor emulsion
Cetyl alcohol + Sodium oleate
Fairly closely packed but no complex formation
Fairly poor emulsion
to fulfilled this 2 criteria must be met
- 2 types of surfactant must interact w one another to form a complex
- they must form a tightly packed film
(2) Formation of an electric double layer
This applies to ionic surfactants.
The electric double layer serves as an electrical barrier to approach of droplets.
(prevent globules from coming together)
3) Increase viscosity of the continuous phase
Gums and waxes (hydrophilic colloid) are commonly used to increase the viscosity of water and oil respectively.
A more viscous emulsion is generally more stable.
formation of rigid interfacial film critria
o fulfilled this 2 criteria must be met
- 2 types of surfactant must interact w one another to form a complex
- they must form a tightly packed film
General theory of emulsion forming w/o thermodynamic factor and the specific theories of forming emulsion
A number of simultaneous process have to be considered as to o/w or w/o emulsion will be form
1) droplet formation
2) aggregation
3) coalescence of droplets
4) interfacial film formation
On shaking together oil and water, both phases initially formed droplets.
The phase that persists in droplets form the longest should become the disperse phase and surrounded by continuous phase formed from the more rapidly coalescing droplets.
The Phase volumes and interfacial tensions will determine the relative number of droplets produced and hence the probability of collision.
eg. The interfacial film produced by adsorption of emulsifier at the o/w interface can alter the rate of coalescence by acting as a physical barrier to coalescence.
The type of emulsion formed depend on the polar/non-polar characteristic of the emulsifying agent. The phase in which it is more soluble being the continuous phase.
Specific theory
1) bancroft theory
2) Harkin Oriented wedge theory
3) angle of contact theory
Explain bancroft theory
A few theories have been proposed to explain the formation of o/w and w/o emulsions.
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.
IF(film/oil) > IF (film/water)
o/w emulsion
IF (film/oil) = IF (film/water) no emulsion
IF (film/oil) < IF (film/water)
w/o emulsion
THEORY DOES NOT APPLY TO HYDROPHILIC COLLOIDS AND FINELY DIVIDED SOLID
Oriented wedge theory explain
ONLY APPLICABLE TO SOUP
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.
The sodium oleate molecule, which is composed of one polar head and one non-polar tail, can be looked upon as wedge-shaped.
These molecules will orientate with their polar heads on the external side of the droplet to allow more molecules to pack at the interface.
As the polar heads are also hydrophilic, this results in the formation of an o/w emulsion.
The magnesium oleate molecule is composed of one polar head and two non-polar tails.
These molecules will orientate with their polar heads on the internal side of the droplet to allow more molecules to pack at the interface.
As the polar heads are also hydrophilic, this results in the formation of a w/o emulsion.
Theory based on angle of contact explain
This applies to emulsifying agents which are FINELY DIVIDED SOLID, 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
If angle is more than 90 = w/o emulsion
angle = 90 = no emulsion
angle = less than 90 = o/w emulsion
what is needed to form emulsion
Oil phase
emulsifying agent
water
Type of oil phase
and the properties to consider
A wide variety of lipids or lipophilic materials such as mineral oils, vegetable oils, silicones and waxes maybe used.
Mineral oil are more stable than vegetable oil coz of unsaturated fatty acid in VO
The following properties of the oil phase are important as they affect the performance of the emulsion: Consistency “Feel” or tactile characteristic Stability Drug solubility
Function of emulsifying agent
Its function is to stabilize the emulsion
class of emulsifying agent
surfactants, hydrophilic colloids and finely divided solids.
Factor affect the selection of emulsifying agent
Factors affecting the selection of emulsifying agents: Type of emulsion (o/w or w/o)
Compatibility with other components
Toxicity of emulsifying agent
Cost of emulsifying agent
what is surfactants and the groups
These compounds have a hydrophilic group and a lipophilic group in their molecular structure.
This amphipathic nature causes the molecules to become attached to interfaces, thereby lowering interfacial tension.
They are divided into four major groups: anionic, cationic, amphoteric and nonionic.
Anionic surfactant
for what use
and types
Generally employed for external preparations. Incompatible with cationic compounds, low pH and high concentration of electrolytes.
Effectiveness enhanced by nonionic surfactants Different types:
1) Soaps of monovalent bases (o/w)
2) Soaps of polyvalent bases (w/o)
3) Amine soaps (o/w)
4) Sulphated and sulphonated fatty acids and alcohols (o/w)
5) Quillaia saponins (o/w)
many drug are anionic so normally we use anionic surfactant
Soap of monovalent base properties
Sodium stearate Potassium stearate Ammonium stearate
form o/w emulsion
properties
- Presence of polyvalent cations will cause phase inversion.
Sodium and potassium soaps have high pH and are unsuitable for emulsions where a high pH cannot be tolerated.
Soap of polyvalent bases properties
Calcium oleate Zinc oleate
w/o emulsion
Presence of monovalent cations will cause phase inversion.
amines soaps properties
Triethanolamine stearate
o/w emulsion
Suitable for o/w emulsions where a high pH cannot be tolerated.
Sulphated and sulphonated fatty acids and alcohols
properties
Sodium lauryl sulphate Sodium cetyl sulphate
o/w emulsion
Generally more effective than other types but strongly alkaline.
SLS + CSA –>Emulsifying Wax
Quillaia saponins
for internal use
o/w emulsion
Glycosides from Quillaja saponaria
Produce o/w emulsions of low viscosity.
Can be employed for oral preparations
Cationic surfactants properties
Possess emulsifying and antiseptic properties. Incompatible with anionic compounds.
Examples include quaternary ammonium compounds, such as cetrimide,cetyl pyridinium chloride and benzalkonium chloride.
Promote the formation of o/w emulsions
FOR EXTERNAL USE
Amphoteric surfactant properties
These surfactants are cationic at low pH and anionic at high pH.
Not widely used.
E.g.lecithinfor I/V fat emulsions.
Non ionic surfactant properties
Low toxicity and irritancy.
Less sensitive to pH changes and addition of electrolytes and polyvalent ions
For external as well as internal preparations.
Types of non-ionic surfactant
Sorbitan esters and polyoxyethylene sorbitan esters (DEPENDS ON HLB)
Glycol and glycerol esters (O/w)
Fatty acid polyglycol esters (o/w)
Fatty alcohol polyglycol ethers (Macrogol ethers) (depend on HLB)
Higher fatty alcohols
sorbitan esters and polyoxyethylene sorbitan esters
Depending on the HLB of the blend, it may promote the formation of o/w or w/o emulsions.
NONionic surfactant
span (sorbitan) and tween (POE)
POE increase hydrophilicity
20,40,60 etc = mono
65,85 = tri
number increase hydrocarbon chain increase so HLB drop
HLB higher = more hydrophilic
glycol and glycerol esters properties
eg
glyceryl monostearate
Promote formation of o/w emulsions.
Effectiveness enhanced by soaps of monovalent bases and amine soaps.
Fatty acid polyglycol esters (POE fatty acid esters)
properties
E.g. POE(40) stearate
Promote formation of o/w emulsions.
Effectiveness enhanced by stearyl alcohol.
Fatty alcohol polyglycol ethers (POE fatty ethers) (Macrogol ethers) properties
E.g. Cetomacrogol 1000
Blends of hydrophilic and lipophilic members are usually employed.
Depending on HLB of the blend, it may promote the formation of o/w or w/o emulsions.
Cetomacrogol 1000 + Cetostearyl alcohol —> Cetomacrogol emulsifying wax
Higher fatty alcohols properties
Auxiliary emulsifying agent
eg cetostearyl alcohol
disadvantage of nonionic surfactant with POE or polyglycol group
incompatible with phenols
as they have higher affinity for phenol than water. thus phenol can displace water and emulsifying agent can PPT out of soln and emulsion become unstable and phenol will lose its intended function.
hydrophilic colloids are
emulsifying agent
These substances are more useful as auxiliary emulsifying agents and as thickening agents.
They generally favour the formation of o/w emulsions.
types of hydrophilic colloids
(1) Natural and synthetic clays
E.g. bentonite
Bentoniteis derived from montmorillonite which is a typical smectite clay. It swells in the presence of water but raises the viscosity of the medium only at pH 6 or higher.
(2) Natural and synthetic gums
E.g. acacia, tragacanth, sodium alginate, carrageenan, locust bean, guar, xanthan, sodium CMC, methyl cellulose
These are polysaccharides.
They exhibit incompatibility with certain cations or pH. Sodium alginate and sodium CMC are incompatible with acids. (Ca salt)
Methyl cellulose is less soluble in hot water.
(3) Proteins
E.g. gelatin, soluble casein
These are less commonly employed than the gums. Gelatin is prepared by partial hydrolysis of collagen.
what is highly divided solid
Not of major interest to the formulator because of their limited utility as primary emulsifying agents. Solids of mineral origin should be sterilized before use because they may contain tetanus spores.
Two types:
(1) Polar inorganic solids
E.g. heavy metal hydroxides, non-swelling clays They favour the formation of o/w emulsions.
(2) Non-polar solids
E.g. carbon, glyceryl tristearate
They favour the formation of w/o emulsions
Additives that can be use
Depending on the purpose of the emulsion, one or more of the following may be employed.
Antimicrobial preservatives
Antioxidants / Chelating agents
Buffers
Colours
Sweetening agents, flavours and fragrance
some oil in emulsion is unstable and prone to oxidation thus producing ketone (smelly)
types of anti-microbial preservative
Emulsions often contain a number of ingredients which readily support the growth of a variety of microorganisms.
The function of antimicrobial preservatives is to reduce microbial contamination of the product.
E.g alkyl hydroxybenzoates (parabens) and benzoic acid and chlorocresol.
desirable properties of a preservative for use in an emulsion are
1) wide spectrum of antimicrobial activity
2) high preservative capacity
3) low oil/water partition coefficient
4) freedom from toxic, irritant and sensitizing activities 5)compatibility with other ingredients and container 6)stability and effectiveness over a wide pH range and temperature range
7) freedom from colour and odour
Antioxidant should be ________
oil soluble so that they can prevent [o] in oil
Their function is to prevent oxidative degradation of compounds
Combinations of two or more antioxidants have been shown to produce synergistic effects.
eg of antioxidant
butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA),L-tocopherol and alkyl gallates
BHT, BHA and alkyl gallates are much more effective in the presence of citric, tartaric or phosphoric acids.
chealting agents example
citricacid,maleicacid, phosphoricacid
Included if traces of metallic ions are likely to catalyse oxidative degradation
function is to remove ion available for [o]
Technique for emulsification
(1)Agent-in-water method
The emulsifying agent is dissolved in water and the oil is then added with vigorous agitation, producing o/w emulsion directly.
For w/o emulsion, the addition of oil is continued until phase inversion occurs.
(2)Agent-in-oil-method
The emulsifying agent is dissolved in oil,which is then added to water with vigorous agitation,forming o/w emulsion.
For w/o emulsion,the addition of oil phase continues until phase inversion occurs.
(3)Nascent soap method
This is 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.
(4) 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 and homogenisation
- Simple stirring — propeller mixer, turbine mixer, paddle mixer
- Colloid milling (most commonly used)
- Vibration and ultrasonification
further homogenization to improve globule to smaller size so as to increase stability.
turbine mixer is most effective.
Emulsion stability factors
stages
A physically stable emulsion is one in which there is no coalescence of disperse phase that ultimately leads to separation of the oil and aqueous phases.
As soon as an emulsion has been prepared, time-and temperature-dependent processes occur to effect separation of the two immiscible phases.
Emulsion instability is shown by creaming, flocculation,
coalescence and/or cracking.
creaming/flocculation = sign of instability
coalescence and cracking = unstable form of emulsion
Creaming explain
Under the 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.
In an emulsion, there are numerous droplets and they mutually interfere.
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.
factors that reduce the rate of creaming and improve stability of emulsion
Factors expressed in the Stokes’ Law that can be used to reduce the rate of creaming and improve the stability of the emulsion.
radius of droplet
viscosity of continuous phase (if is o/w can add gum, if is w/o can add wax)
difference in densities of the disperse phase and continuous phase
An increase in the volume fraction of the disperse phase has also been found to reduce the rate of creaming.
flocculation explain
This refers to 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.
The aggregates behave as single particles and therefore increase the rate of creaming.
coalescence
The droplets join to form larger drops.
This process is irreversible, leading to a decrease in the number of droplets and finally cracking.
cracking
This refers to a complete breakdown of the emulsion, with coalescence of the droplets and a separation of the two phases into two layers.
This process is irreversible.
Cracking may result from chemical, physical and biological effects.
Addition of substances incompatible with the emulsifying agent
pH changes
Temperature changes
Bacterial and fungal action
what is HLB
A surfactant consists of a hydrophilic group and a lipophilic group in its molecular structure.
The ratio of these two groups affects the water or oil solubility of the surfactant.
This ratio is called the hydrophile-lipophile balance.
The higher the HLB number, the greater the hydrophilic property and vice versa
HLB = ( Weight of hydrophilic group / MW ) X 20
HLB 4-6 application
w/o emulsifing agent
HLB 7-9 application
wetting agent
HLB 8-18 application
o/w emulsifying agents
HLB 13- 15 application
detergents
HLB 10-18 application
solubilizing agents
w/o emulsifing agent HLB
HLB 4-6
wetting agent HLB
HLB 7-9
o/w emulsifying agents HLB
HLB 8-18
detergents HLB
HLB 13- 15
solubilizing agents HLB
HLB 10-18
how many emusifier to have
better to have a mixture of emulsifiers,
one of lower HLB than required and other of higher HLB than required.
as a blend of surfactants is more effective than a single surfactant.
HLB of the blend = required HLB
significant of HLB concept in formation of emulsion
It provides a guideline to select an appropriate surfactant blend to produce a stable emulsion.
Formula given:
Liquid paraffin 35% (HLB 12)
Wool fat 1% (HLB 10)
Cetyl alcohol 1% (HLB 15)
Surfactants 5% (span 80; HLB 4.3 &
tween 80; HLB 15)
Water to 100%
Calculate HLB required for o/w emulsion
35/37 X 12 = 11.4
1/37 X 10 = 0.3
1/37 X 15 = 0.4
total = 12.1
A/100 (4.3) + (100-A)/100 X 15 = 12.1
0.043 A + 15.0 - 0.15 A = 12.1
0.107 A=2.9
A = 27.1%
Span 80 required = 27.1% X 5 = 1.36%
Tween 80 required = (1-0.271) X 5 = 3.64%
OR
P/5 (4.3) + (5–P) / 5 (15.0) = 12.1
4.3P + 75.0 - 15.0P = 60.5
10.7P = 14.5
P = 1.36
Amount of Span 80 required = P= 1.36%
Amount of Tween 80 required = 5-P =3.64%
How to make emulsion
(1) Calculate the required HLB for the o/w emulsion
(2) Select the surfactants and calculate the amounts required
(3) Determine the optimal HLB and surfactant blend
The emulsifying efficiency of the surfactants is affected by various factors which may not be taken into consideration by the HLB concept. Hence, the required HLB calculated may not be the optimal.
Therefore, in the formulation of a given emulsion, one usually selects a pair of surfactants and vary the proportion to give values of HLB over the range in which they would be expected to be effective.
Studies have also shown that different blends of surfactants with the same HLB value may exhibit varying emulsifying efficiency.
Therefore, having found the most effective HLB, one would try various pairs of surfactants until the most effective pair is found.
Colour of O/W vs W/O emulsion
O/W is usually white
W/O assume colour of the oil
feel on skin compare emulsion
o/w initially not greasy
w/o greasy
Filter paper wetting compare emulsion
o/w diffuse rapidly
w/o diffuse slowly
filter paper impregnated with cobalt chloride compare emulsion
o/w = filter paper changes from blue to pink w/o = filter paper remain blue
fluorescence compare emulsion
o/w = Exhibits dot pattern under UV light w/o = fluoresces throughout
conductivity emulsion compare
o/w = conducts electricity w/o = poor or non-conducting
Dye test emulsion compare
o/w = globules colored by oil-soluble dye while continuous phase by water-soluble dye (methylene blue)
w/o = globules colored by water soluble dye while continuous phase by oil-soluble dye (sudan III)
Dilution emulsion compare
o/w = miscible with water w/o = miscible with oil
methods for determination of emuksion type
Colour feel on skin filter paper wetting filter paper impregnated with cobalt chloride fluorescence conductivity dye test dilution
Assessment of emulsion stability
the emulsion subjected to both accelerated and traditional methods (just leave at ambient condition)
acceleratd methods
1) centrifugation (3750RPM for 5hr in 10cm centrifuge is
= 1 year gravity)
2) Agitation (shake)
3) Freeze - thaw cycle (-25 to 25 back to -25 degree = shld withstand 2-3 cycles)
3) heating - cooling cycle (45 to 5 back to 45 degree)
= should withstand 6 cycles)
Type of tests for assessment of emulsion stability
1) 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 separation of phases during its prescribed shelf-life.
(2) 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 - need measure 635 globules) 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.
(3) 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.
(4) 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.
