emulsions Flashcards
define emulsions
system w two immisicible liquid phases , one dispersed as fine globules throughout the other
stabilised by EA
globules called
liquid called
disperse or internal phase
continuous or external phase
+ve of emulsions
- easy to swallow
- mask objectionable taste
- enable iv adm of lipid nutrients
- cost advantage over certain single phase preperations
solvents for lipids are more costly than water - high degree of flexibility bc can vary oil water ratio
- topical emulsions elegant
-ve of emulsions
stable emulsions are harder to formulate
bulky
prone to microbial contaminations - lead to cracking
uniform dose may not be achieved
4 types of emulsions
simple
multiple
micellar
microemulsions
what are simple emulsions
oil globules dispersed in water
water globules dispersed in oil
what are multiple emulsions
water-in-oil-in water ( w/o/w) emulsion
- wtaer in oil primary emulsion dispersed in water
oil-in-water-in oil (o/w/o) emulsion
o/w primary emulsion dispersed in oil
what are microemulsions
extremely small globules dispersed in continous phase
- 10-75 nm
- cant be seen by naked eye
what are micellar emulsions
and 2 types
- relatively high conc of surfectant
- small prop of disperse phase solubilised by the surfactant/ micelles
- surfactant exists as micelles v small cannot be seen by naked eye 5-20nm
- oil-in-water emulsion
- oil found in the non-polar interior of the micelles present in an aqueous continuous phase - reverse micellar emulsion
consists of water which is found in the polar interior of the micelles which are present in an oily cont phase
( water disperse and oil continuous)
3 ways to differentiate o/w and w/o
- feel on skin
initially non-greasy to greasy - o/w
greasy from beginning - w/o - dye test using oil soluble sudan III dye
add dye and mix then examine sample
if globules stained then globules oil = o/w
if cont phase stained then thats oil = w/o - dilution methods
add water to text tube and add emulsion then mix gently
miscible with water - o/w
if not w/o
what are the 3 basic components of an emulsion
oil, water and emulsifying agent
types of materials used in oil phase and 2 common
oils
mineral oils
vegetable oils
silicones
waxes
diff between vege and mineral oil
vege
- used for oral
- used for topical
- can turn rancid
- unpleasant odour
mineral oil
- more stable than vege
4 properties to consider for choosing of oil phase
consistency - viscosity
feel or tactile characteristics
stability
drug solubility - if oil is a carrier for the drug then drug shld be able to dissolve in oil/ oil shld be able to solubilise the drug
what is emulsifying agent known as
what is it used for
- aka emulgent
- used to stabilise the emulsion , it acts as an interfacial film between the continuous and disperse phase
3 classes of emulsifying agents ( EA )
surfactants
hydrophilic colloids
finely divided solids
4 factors that affect which EA to use
- type of emulsion u want whether o/w or w/o
- compatibility with other components eg drugs or preservatives
- toxicity of EA
- cost of EA ( influential but not decision maker )
most EA exist as
powders
structure of surfactants
- func
and 4 types
- hydrophilic and lipophilic grp
- amphipathic nature
= they become attached to interfaces
= lowering the interfacial tension
4 main grps
- anionic
- cationic
- nonionic
- amphoteric
anionic surfactants can be used for
external preperation
- preperations that dont have cationic compounds , low ph , and high conc of electrolytes
anionic surfactants effectiveness enhanced when used with what and give example
used w nonioninic surfactants
eg sodium lauryl sulphate and sodium cetyl sulphate
4 types of anionic surfactants
soaps of monovalent bases
soaps of polyvalent bases
amine soaps
sulphated and sulphonated fatty acids and alcohols
soaps of monovalent bases
examples
- type of emulsion formed
- properties
eg :
- sodium , potassium or ammonium stearate
form o/w
prop :
- ensure no polyvalent cation present or will cause phase inversion
- sodium and potassium cannot be used if u want to end up with a low pH emulsion bc sodium & potassium soaps have high ph
which anionic surfactant to use if want low ph
amine soaps
how are soaps forms
fatty acid + ester ( soap )
oleates and stearates are examples of fatty acids
soaps of polyvalent bases
examples
which emulsion fo they form
and properties
eg calcium and zinc oleate
form w/o
- presence of monovalent cations cause phase inversion
amine soaps examples , type of emulsion formed
and properties
eg triethanolamine stearate
forms o/w
- suitable if need a low ph end product
sulphonated and sulphonated fatty acids and alcohols
eg and properties
eg sodium lauryl sulphate
sodium cetyl sulphate
SLS + CSA => forms emulsifying wax
forms o/w
- more effective than others but
strongly alkaline
cationic surfactants examples
- properties
- incompatible with
- forms what emulsion
eg
- quaternary ammonium compounds such as cetrimide, cetyl pyridinium chloride and benzalkonium chloride
properties - has emulsifying and antibiotic properties
( used mostly for its ab properties )
incompatible with anionic compounds
- forms o/w - similar to anionic
amphoteric surfactants properties and
example
+ use
cationic at low ph and anionic at high ph
eg lecithin for I/V fat emulsions
not widely used
non ionic surfactants
properties
use
v commonly used ! like anionic
- low toxicity & irritancy
- not charged so less sensitive to ph changes and addition of electrolytes
used for external and internal
types of nonionic surfactants
sorbitan esters ( SPAN ) polyoxyethylene sorbitan esters ( TWEEN)
higher fatty alcohols
others:
glycol and glycerol esters
fatty acid polyglycol esters
fatty alcohol polyglycol ethers ( macrogel ethers )
what to note abt span and tween trends as
numbers inc
numbers inc = indicating longer or greater hydrocarbon chain
= more lipophilic
= lower the HLB
spans are more lipophilic surfactants and have lower HLB < 9
tweens have POE grp which give hydrophlicity
tweens are hydrophilic surfactants and have higher HLB as a result
hlb have higher tween values generally 11-16 ish
example of a higher fatty alcohol ( example of nonionic surfactant )
and its use
cetostearyl alchol ( CSA ) -known as an auxillary emulsifying agent
- not effective ea on its own but useful when combined with anionic surfactant
what to note about phenolic compounds
if using phenolic compound as a preservative
DONT USE NON IONIC SURFACTANT that consists of a POE grp - dont use tween!!
bc poe grp can form hydrogen bonds with phenolic compounds
= no longer performs its function as a preservative
what are hydrophilic colloids
how do they compare to surfactants
what can they be used for
what do they form
2nd class of emulsifying agents
- NOT AS EFFECTIVE AS SURFACTANTS
- used to make oral preperations
useful as auxiliary emulsifying agent and thickening agent
- generally favour the formation of o/w emulsion
3 types of hydrophilic colloids and which is the most common
clays gums and proteins
gums most common eg acacia , tragacanth , sodium alginate
eg of clays - bentonite clay
eg of proteins - gelatin or soluble casein
properties of clays
swells in presence of water
raises viscosity of medium at pH 6 or higher
examples of gum and
their properties to take note of
acacia, tragacanth, sodium alginate , sodium CMC
sodium alginate and sodium CMC incompatible with acids
methyl cellulose less soluble in hot water
finely divided solids
what is it and
2 what to look out for
- last class of EA , not commonly used for pharmaceuticals
solids of mineral origins must be sterilised bc may contain tetanus spores
2 types of finely divided solids
and their properties
- polar inorganic solids
- heavy metal hydroxides, non swelling clays
- favour formation of o/w emulsions - non-polar solids
eg carbon, glyceryl tristearate
favour formation of w/o emulsions
why are emulsions thermodynamically unstable
tension exists at the droplet interface bc the two phases ( which are immiscible ) have different attractive forces for a molecule at the interface
- on standing the droplets gradually coalesce to minimise tension in the system which will result in phase seperation
- therefore EA used
explain how EA forms stable emulsions thru interfacial film
key concept :
EA form tightly packed film = stable emulsion
regardless of the complex formation
cholesterol + sodium cetyl sulphate
= closely packed condensed complex => stable emulsion
olelyl alcohol + sodium cety suphate
loosely packed condensed complex
- poor emulsion
cetyl alcohol + sodium oleate
fairly closely packed but no complex formation
- fairly poor emulsion
explain how EA forms stable emulsions thru electric double layer
– which surfactant is this applicable for
- only for ionic
- forms electric double layer around the droplet
- prevents droplets from coming close to one another
- prevents coalesce - prevent phase seperation
explain how EA forms stable emulsions thru increasing viscosity
gums added to water
waxes added to oils to inc the viscosity of each respectively
more viscous continous phase prevents coalescence of the disperse phase droplets
= more stable emulsion formed
what is bancrofts theory and applicable to what
applies to surfactants as EA
- adsorption of surfactants at the interface forms the interfacial film
- film experiences 2 interfacial tensions , one btwn film and aq and one btwn film and oil phase
- film will curve in the direction of greater interfacial tension
= disperse phase is on the side of the film with the higher interfacial tension
IF film/oil > IF film/water -> o/w
IF film/oil < IF film/water -> w/o
if both equal = no emulsion
whats oriented wedge theory/harkin and used for what
exclusive to soaps as EA ( which are anionic surfactants )
- surfactant molecules ( soaps) will migrate to the interface and orientate themselves to form a tightly packed film
- location of the polar heads determines the type of emulsion formed
sodium oleate in harkins theory
monovalent base - promoting o/w one polar head and one non polar tail - looked upon as wedge-shaped - will orientate their polar heads on the external side of the droplet for more moelcules to pack at the interface - since polar head outside , oil inside
look at pic if needed
magnesium oleate in harkins theory
divalent base soap
- composed of one polar head and two non-polar tails ( tails > wider than head )
- molecules will orient their polar heads on the internal side for more molecules to pack
since polar head inside, hydrophilic, w/o emulsion
what’s the theory based on angle of contact
applicable to which ea
what are the 4 conditions
- only applicable to finely divided solids
with
1. insoluble in both aq and oily phases
2. preferentially wetted by one phase
3. able to form a thin interfacial film
4. of colloidal size eg < 1micron in size - these solid particles attracted to the interface
- angle of contact formed determines type of emulsion produced
angle formed with oil aBOVE water - tangent drawn and take the above angle from tangent to the particle > 90 = w/o =90 = no emulsion < 90 = o/w
what does the hlb concept show
surfactant has lipophilic and hydrophilic grp in the molecular structure
allowing it to migrate to the interface
ratio of these 2 grps affects the water or oil solubility
ratio known as hydrophilic-lipophilic balance
greater hlb number means what
and what does 20 mean
means more hydrophilic
( therefore tween higher than span bc of PEG )
20 hypothetically represents a molecule which is 100% hydrophilic
how to calculate HLB
( weight of hydrophilic grp/ mr ) x 20
hlb of 15 represents a molecule containing 75% by weight of hydrophilic grp
HLB ranges and application
4-6 - w/o EA 7-9 - wetting agents 8-18 - o/w EA 13-15 - detergents 10-18 - solubilizing agents ( used to inc apparent solubility of compounds in water )
calculation of required hlb
and calculation of required surfactants
- identify component of oil phase
- calculate proportion of each oil components of the total oil phase
- find required hlb of each oil phase component by multiplying hlb x proportion
- tally up total to get the required hlb
req surfactants amt calculation - note % of surfactants - let amt of 1 surfactant be X - let other be 1-x - x/% . hlb + (1-x)/% . hlb = required hlb from above calculate out x and 1-x
how to determine the optimal hlb and surfactant blend
- select pair of surfactants and vary proportion to give values of HLb over a range in which they would be expected to be effective
- after finding the most effective hlb
- vary the pair of surfactants used @ this hlb
and find the most effective pair
this is bc hlb concept dosent consider various other factors affecting the efficiency of the emulsion
common additives added in formulation of emulsions
- buffers to control ph esp when stability of drug affected by ph
- colour for appearance
- sweetening agents or flavours for oral
- fragrance for smell
- antimicrobial preservatives for multi dose preps
- antioxidants or chelating agents if ingredient is easily oxidised
agent in water emulsification method
ea added to water
oil added in with vigorous aggitation , producing o/w directly
continue adding oil = phase inversion
forming w/o
or could be oil in bucket and ea with water added to that
first would be w/o then phase inversion
agent in oil emulsification method
ea added to oil which is then added to water( in bucket ) with vigorous agitation
forms o/w
continue adding oil = form w/o
nascent soap emulsification method
and what does it produce
- useful for soaps as EA ( bc soaps are fa + base )
fatty acid dissolved in oil
base dissolved in water
soap formed in situ and functions as EA
forming the emulsion
emulsion formed depends on the type of soap formed
monovalent soap - forms o/w
polyvalent soap - forms w/o
alternate addition method of emulsification
- not commonly used
- used particularly for vege oils
water and oil added alternatively in small amounts to the emulsifying agent ( in bucket )
o/w or w/o formed depending on the ratio of w vs o
what are the types of emulsifying machines
simple stirring - propeller mixer ( common ) turbine mixer( hooge ) and paddle mixer ( preferred for stable emulsions )
colloid mixing
vibration and ultrasonification
how does a colloid mill work
look @ pic if needed
mixture of oil and water from hopper to rotor which is corrugated channels rotated @ high speed
passed down @ stator as homogenised particles and passed back up to go thru the whole process again and get even more homogenised
when is a emulsion physically stable
no coalescence of disperse phase leading to separation of the phases
what processes occur to cause seperation of the phases
time and temp dependant processed
what 4 processes show instability in a emulsion
creaming, flocculation - reversible
coalescence and or cracking
what is creaming and what can be used to form strategies to
prevent this
creaming is when globules tend to rise or sediment depending on the difference in specific gravities of the phases under the influence of gravity
- conc of disperse phase at the top or bottom of the system
but reversible upon shaking - gets redispersed
STOKES LAW
STOKES LAW EQN and terms
+ what assumptions/ applies to what
v = 2r^2 ( p1-p2)g / 9n
velocity of fall or rise of droplet radius of droplet density of disperse phase is p1 density of continuous phase is p2 gravitational constant g viscosity of continuous phase is n
applies to isolated sphere in an infinitely large mass of liquid
- cannot calculate creaming rate from this bc inreality theres many spheres and one globule can affect the others / mutuallu interfere
but can form strategies to influence creaming rate
why cant stokes law be used to calc creaming rate
emulsion has numerous droplets and they mutually interfere
- hindrance to motion depends on the conc of the droplets of the disperse phase and this in turn depends on the volume fraction of the disperse phase
= therefore cannot be directly used to calc
but can be used to reduce rate of creaming
+ improve stability
3 strategies ( from stokes law ) to reduce creaming rate and improve stability
- radius , dec radius , dec velocity so
shear or agitate more for smaller droplet size - inc viscosity of the cont phase to dec creaming rate
for o/w add hydrophilic colloid eg gum
for w/o add wac - reduce the difference in densities of the disperse and cont phase p1 and p2
( but not commonly used bc hard to modify )
or inc volume fraction of the disperse phase
what is flocculation
reversible aggregation of droplets in disperse phase to form 3d clustered
- they remain as droplets due to mechanical or electrical barrier arounds the droplets which prevents coalescence but they just form clusters
- these clusters behave as single particle and inc droplet size = inc r
= inc rate of creaming
what is coalescence
droplets joining to form larger drops
irreversible
= dec in number of droplets
= eventually leads to cracking
what is cracking
complete breakdown of emulsionn coalescne of droplets and seperation of the 2 phases into 2 layers irreversible may result from chem,physical and biological effects such as - addition of incompatible substances - ph changes - temp changes - bact or fungal action
5 examples of incompatible substance addition leading to cracking
- strong acids + alkali- metal soaps
bc no longer alkali and no longer exert EA func to stabilise emulsion - anionic compounds w cationic surfactants
- cationic compounds w anionic surfactants
- high conc of electrolytes + soaps
- alcohol and gums bc
alc precipitate gum and no gum no longer able to serve as an EA
how to asses emulsion stability 2 main methods
- based on changes in specific properties like conductivity, viscosity, size of droplets
- traditional method - subject to storage @ ambient conditins based on predicted shelf life then determine changes to properties
but time consuming altho more realistic - accelerated method - sped up stress test
eg centrifugation 3750rpm 5hr in 1cm radius centrifuge
agitation - controlled agitation
freeze thaw cycles- -25. 25 deg
repeat cycles then count no of cycles before cracking
heating and cooling cycles 45 , 5 deg
what to note about stress tests to test stability
dont subject to excessive stress
bc abnormal processes may come into play
and the results obtained may not be meaningful
test to determine degree of seperation
let it stand and calc ratio of the volume of seperated phase over total volume of emulsion
stable emulsion shld not show any seperation for its prescribed shelf life
size analysis of glubuesl
gradual coalescne affects the size of globules
faster the change of globule size =
more unstable
methods ( more effective ) - coulter counter - laser diffraction technique less effective - microscopic examination , electronic particle counting method
determination of electrophoretic property aka conductivity
+ how to aid the measurements
greater the change in conductivity
= more unstable
w/o - poor conductivity
conducitivity indicates water droplet aggregation and instability
o/w - good conductivity
so reduction in conducitivity shows oil droplet aggregation and instability
measurements made with the aid of platinum electrodes, on emulsions stored for short periods of time
determination of viscosity changes
+ what is used to measure
viscosity affected by globule size and number
so changes to viscosity chan be used to show changes in emulsion stability
- measure using viscometers
more rapid change - more unstable
draw the graph of viscosity change for ideal, typical and abnormal
ideal is small inc and stable line
typical is small inc then gradual inc over time
abnormal is weird kink or curve
small inc due to the energy stored in the system , bc system takes time to stabilise
what is the expected shelf life of emulsion
18 months
so must test to ensure stable for this shelf life
can we preserve emulsion stability using a fridge
if temp too low, ea may be affected bc solubility exceed temp
and for ea to work it must be in solution
so if the amt of ea remaining is insuffieicnt then it wont be stable so it depends
not all can be stored in the fridge
