Emulsions Flashcards
What is an emulsion?
a dispersed system containing at least two immiscible liquids
-one of the liquids (internal phase) is finely subdivided and uniformly distributed as droplets throughout the other (external phase)
-one of the liquids is aqueous, while the other is oleaginous
What is the size of droplets in an emulsion?
0.1-100um
What are the types of emulsions?
two phase system
-oil in water (o/w)
-water in oil (w/o)
multiple emulsions (emulsions within emulsions)
-w/o/w emulsions
-o/w/o emulsions
Differentiate between the two types of two phase systems for emulsions.
oil-in-water (O/W) emulsions
-an emulsion in which the oil is dispersed as droplets throughout the aqueous phase (water >45% of total weight)
water-in-oil (W/O) emulsions
-an emulsion in which water is the dispersed phase and an oil is the continuous phase (water <45% of total weight)
Why were multiple emulsions invented?
to produce a sustained release of the active ingredient
-a drug in the innermost phase must cross two phase boundaries to reach the external or continuous phase
Differentiate between the two types of multiple emulsions.
W/O/W
-small water droplets which are enclosed in a large oil droplet, which is dispersed in water
O/W/O
-small oil droplets are enclosed in a large water droplet, which is dispersed in oil
What are the advantages of emulsions?
aqueous phase easily flavoured
oily sensation easily removed
unpalatable drugs can be made palatable
increased rate of absorption (no dissolution)
swallowed easier than tablets or capsules
possible to include two incompatible ingredients
parental administration where lipid component is important
What would be the choice of emulsion type for the following routes of administration and why?
-oral
-intravenous
-intramuscular
-external
oral: o/w
-ensures pleasant taste
intravenous: o/w
-otherwise serious embolization may occur
intramuscular: w/o
-depot therapy (sustained release)
external: o/w or w/o depending on desired use
-emulsified lotions, creams, or liniments
List off some physical differences between o/w and w/o emulsions.
o/w
-not greasy
-water washable
w/o
-greasy
-occlusive
-form water repellent film
What is the most common route of administration that utilizes emulsions?
topicals
-lotions: fluid emulsions (o/w)
-creams: vanish upon rubbing (o/w or w/o)
-ointments: occlusive, non-water washable and greasy (w/o)
What are the three components of an emulsion?
oil phase
water phase
emulsifying agent
What are the possible choices of an oil phase for the following routes of administration?
-oral
-intravenous
-external
oral:
-liquid paraffin
-castor oil
-cod liver oil
-arachis oil
intravenous:
-cottonseed oil
-safflower oil
-soya bean oil
external:
-turpentine oil
-benzyl benzoate
-various oils
Differentiate between fixed oils, essential/volatile oils, and mineral oils and provide examples of the ones we must know.
fixed oils: non-volatile, fatty oil of animal or plant origin
-castor oil, cod liver oil, olive oil
essential/volatile oils: non fatty oils from plants
mineral oils: a grade of liquid petrolatum
-liquid paraffin
What are some possible choices for the water phase of an emulsion?
water
glycerol
propylene glycol
polyethylene glycols
What does an emulsifying agent do?
mixes aqueous phase and oil phase (with the help of energy)
-reduces interfacial tension
-imparts a charge on the droplet–>electrostatic repulsion
What are the requirements for emulsifying agents?
molecular structure
stable interface
chemical stability
inertness
non-toxic, non-irritating
odorless, colorless, tasteless
not cost-prohibitive
What are the two ways we classify emulsifying agents?
based on chemical structure
-synthetic and semi-synthetic
-natural
-finely dispersed solids
-auxiliary agents
based on mechanism of action
-surface active agents
-hydrophilic colloids
-finely divided solid particles
Further classify emulsifying agents based on structural classification.
natural
-plant derivatives
-animal derivatives
semi-synthetic (cellulose derivatives)
synthetic
-polymers
-surfactants (anionic, cationic, non-ionic, zwitterionic)
finely divided solids
auxiliary emulsifiers
Describe natural emulsifying agents.
plant derivatives (mainly water soluble natural polymers) such as tragacanth or xanthan gum
animal derivatives like gelatin, lanolin (w/o), cholesterol and lecithin
concerns of bacterial contamination
Describe semi-synthetic emulsifying agents.
cellulose derivatives (mainly water soluble polymers)
-methylcellulose and carboxymethylcellulose
Describe synthetic emulsifying agents.
polymers like PVP, PEG, or carbomer
surfactants: can be further divided based on the hydrophilic part of their structure
-anionic (soaps and detergents)
-cationic
-non-ionic
-zwitterionic
Describe anionic surfactants.
hydrophobic tail and hydrophilic head (head has -ve charge)
soft soaps: alkali metal and ammonium soaps, o/w emulsions
-monovalent (Na, K, NH4, triethanolamine-sterate)
hard soaps: divalent and trivalent metals, w/o emulsions
-calcium oleate
detergents: sulfated and sulfonated compounds, o/w emulsions
-sodium lauryl sulfate
Describe cationic surfactants.
hydrophobic tail and hydrophilic head (head has +ve charge)
quaternary ammonium compounds like benzylalkonium chloride
can be used as preservative
What is benzylalkonium chloride used for?
preservative in ophthalmic formulations
Describe non-ionic surfactants.
most common surfactants
hydrophobic tail and hydrophilic head (no charge)
contains an OH and/or ethylene oxide group–>hydrophilic moiety
fatty acid or alcohol (12-18C)–>hydrophobic moiety
spans and tweens
What determines the solubility of non-ionic surfactants?
hydrophobic portions predominates–>surfactant is oil-soluble
hydrophilic portion predominates–>surfactant is water-soluble
Are spans or tweens more hydrophilic?
tweens: more hydrophilic
spans: less hydrophilic
Describe ampotheric (zwitterionic) surfactants.
carry both a +ve and -ve charge
cationic part–>primary, secondary, or tertiary amines or quaternary ammonium
anionic part–>variable
Describe finely divided solids as emulsifying agents.
minimized inter-particle interactions
most support o/w emulsions, some like bentonite can form w/o emulsions
viscosity depends on the internal concentration
ex: bentonite, veegum
Describe auxiliary emulsifiers.
not first choice of emulsifier
weak emulsifiers=used in combo with other emulsifiers
stabilize the system by thickening (increasing viscosity)–>retard inter-particle movement
ex: fatty acids (stearic acid), fatty alcohols (cetyl alcohol), fatty esters
How do we decide the choice of an emulsifying agent?
depends on the emulsifying ability desired and toxicity
-non-ionic: less toxic, less irritant
-ionic: should not be given orally
–>cationic: toxic at low conc,=limit to external use
–>anionic: high pH=unsuitable for broken skin
-parenteral use: non-ionic surfactants
Differentiate emulsifying agents according to mechanism of action.
mono-molecular film (surface active agent)
-reduces the surface interfacial tension
multi-molecular film (hydrocolloids)
-no change in interfacial tension
-protects coalescence by: sheath around droplets, imparting charge to droplets (repel each other), wetting to increase viscosity (less likely to merge)
solid particle film (finely divided solids)
-increases viscosity–>retard droplet movement
What does amphipathic mean?
a chemical entity which possesses two distinctly different characteristics, such as a molecule which has both hydrophobic and hydrophilic characteristics
What is interfacial tension?
the force causing two immiscible liquids to resist mixing
surfactants lower interfacial tension
What is the critical micelle concentration?
the concentration of surfactants above which micelles form and all additional surfactants added to the system will form micelles
What is the aggregation number?
the average number of surfactant monomers in a spherical micelle
What are the characteristics of micelles?
non-ionic surfactants form micelles at conc «ionic surfactants
in dynamic equilibrium with monomeric surfactant molecules in the emulsion
diameter is dependent on geometry and length of surfactant
Why do we want a high CMC?
surfactant will form micelles before oil (or water) droplets can be coated if CMC is low
Which emulsions are formed from hydrophilic emulsifiers? What about lipophilic emulsifiers?
o/w
w/o
Describe the HLB system.
assigns each surfactant an HLB number (its relative polarity)
numerical scale ranging from 1-50
most surfactants fall between 1-20
HLB numbers (0-10)=lipophilic surfactant
HLB numbers (10-20)=hydrophilic surfactant
What is the HLB value for o/w emulsions? What about w/o emulsions?
8-16
3-8
What are the HLB values for spans and tweens?
spans (fatty acid esters): 1.8-8.6
tweens (hydrophilic): 10.5-16.7
When making an emulsion, which phase is dropped into the other phase?
water phase goes into oil phase slowly
What are the additives for emulsions?
antioxidants
preservatives
humectants
Describe antioxidants as emulsion additives.
used to prevent oxidation of oil and lipid components of the emulsion (rancidity)
BHA and BHT are true antioxidants which are synergistic with certain chelating agents
What are examples of antioxidants?
BHA
BHT
a-tocopherol
alkyl gallates
ascorbic acid
ascorbyl palmitate
Describe preservatives as emulsion additives.
used to prevent growth of microorganisms
often lipid and water soluble preservatives are combined
-methylparabens (water) and propylparabens (oil)
emulsion ingredients may inactivate preservatives
What are examples of preservatives?
benzoic acid, parabens, chlorocresol
quaternary ammonium compounds
organic mercurial compounds
Describe humectants as emulsion additives.
compounds which absorb water from air
used to reduce evaporation of the water phase (prevent drying)
What are examples of humectants?
propylene glycol
glycerol
sorbitol
What are the different formulation methods for emulsions?
dry gum method
wet gum method
in situ soap formation
surfactant-based emulsions
What is special about in situ soap formation?
emulsifying agent is formed fresh inside the solution
What are some examples of equipment used for emulsification?
mechanical stirrers (rotating blades)
-low viscosity preparations
-large quantities may be mixed
homogenizers
-limitation: not suitable for viscosity >2000cP
ultrasonifiers
-ultrasonic waves to break down emulsified droplets
-produce a uniform emulsion
colloid mills
-frequently used
What could be some important AUX labels to include on emulsions?
shake well
+/- for external use only
may or may not be refrigerated
What is the most important requirement of a well-formulated emulsion?
physical stability
-dispersed droplets retain their original characteristics and remain uniformly distributed throughout the continuous phase
What are the phenomena associated with physical instability of emulsions?
creaming or sedimentation
flocculation
coalescence (breaking, cracking)
Describe creaming and sedimentation.
droplets may move upward (creaming) or downward (sedimentation)
direction of movement is determined by density of the droplets relative to density of the continuous phase
increase the possibility of coalescence of adjacent droplets
Why is creaming/sedimentation undesirable?
emulsified product wont be homogenous to deliver a correct dose
What is the equation for stokes law?
V=d^2(po-pw)g/18n
V: velocity/rate of sedimentation (cm/s)
d: diameter of spherical particles (cm)
po: density of oil phase (g/cm3)
pw: density of medium/vehicle (g/cm3)
g: acceleration due to gravity (981cm/s2)
n: viscosity of the dispersion medium
What will reduce the rate of creaming/sedimentation?
decreased droplet size
decrease in the density difference between the two phases
increased viscosity of the continuous phase
control of the disperse phase concentration
True or false: emulsions which have creamed or sedimented will not have good re-dispersibility
false
Differentiate the secondary minimum, primary maximum, and primary minimum.
secondary minimum:
-easy dispersion (close to neutral area)
primary maximum:
-repulsion>attraction
-ideal state of dispersion
primary minimum:
-lowest energy state, particles reside
-difficult to re-disperse
What is coalescence?
complete fusion of droplets within an emulsion, leads to a decreased # of droplets and separation of the two immiscible phases
How is resistance to coalescence provided in emulsions?
o/w emulsions:
strength of mono or multimolecular films
w/o:
-long hydrocarbon chains of surfactant molecules which project into the oil phase
What is the BUD for water containing preparations and external use preparations? Where should oral preparations be stored?
water containing: 14 days
external use: 1 month
oral emulsions should be stored in the fridge
What is the most used anionic surfactant for topicals?
sodium lauryl sulfate (anionic)
How are micelles formed?
self-assembly of amphiphilic molecules (surfactants)
Differentiate Spans and Tweens.
Spans:
-sorbitan fatty esters
-low HLB values (1.8-8.6)
Tweens:
-polyoxyethylene derivatives of Spans
-more hydrophilic, higher HLB (10.5-16.7)
True or false: combination of surfactant in specific ratios will produce a more stable emulsion
true
mixture of surfactants with high and low HLB values
What is an example of a preservative being inactivated by an emulsion ingredient?
micellar binding of preservatives with surfactants (ex: parabens and Tweens)
What is the cause of coalescence and what is the remedy?
cause:
-d large, n low, low CMC, not right surfactant
preventative only (cant be fixed)
What is the cause of creaming and what is the remedy?
cause:
-d large, n low, low CMC, not right surfactant
remedy:
-decreased d, increase surfactant conc, appropriate amount of emulsifier, select correct surfactant
What is the cause of excessive foaming and what is the remedy?
cause:
-too high conc of surfactant, excessive mixing
remedy:
-reduce surfactant conc, avoid air incorporation
What is the cause of microbial growth and what is the remedy?
cause:
-complexation of preservation, too low conc
remedy:
-add suitable preservative, use appropriate conc
What is the cause of unpleasant taste and what is the remedy?
cause:
-inadequate masking, too much surfactant, too low conc of sweetener
remedy:
-use appropriate sweetener, appropriate conc of surfactant
