Emulsions Flashcards
What is an emulsion?
An emulsion is defined as 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)
Describe the composition of Oil-in-Water (O/W) Emulsions
An emulsion in which the oil is dispersed as droplets throughout the aqueous phase (water makes up more than 45% of the total weight)
Describe the composition of Water-in-Oil (W/O) Emulsions
AN emulsion in which water is the dispersed phase and an oil is the continous phase (dispersion medium is less than 45% of total weight)
Is the internal phase larger than the external phase in terms of total weight?
No, the external phase usually larger than the internal phase in most cases, but exceptions exist
What are multiple emulsions?
“Emulsions within emulsions”
They are designed to slow down rapid release because the the drug has to pass through more than one phase boundary
What are two examples of multiple emulsions?
- W/O/W Emulsions:
Small water droplets enclosed in larger oil droplet, which in turn is dispersed in water - O/W/O Emulsion:
Small oil droplet enclosed in a large water droplet, which in turn is dispersed in oil
What are the advantages of emulsions as dosage forms?
- Better drug absorption when drug is found within oil droplets
- Can deliver drugs with poor water solubility via the oral route
- Patients that have difficulty swallowing may benefit from the liquid
- Easier to mask unpalatable tastes and can be flavoured
- Used in parenteral administration due to the lipid content of W/O Emulsions
- Possible to deliver two incompatible drugs in the different phases of an emulsion
What are the four administration routes for emulsions?
- Oral Administration (mostly O/W to ensure a pleasant taste)
- Intravenous Administration (must be O/W)
- Intramuscular (depot therapy)
- External Administration (lotions, creams, etc.)
What is the most popular administration route for emulsions?
Topical (external administration)
What are the physical properties of O/W emulsions?
Not greasy
Water-washable
What are the physical properties of W/O emulsions?
Greasy
Occlusive
Form water repellent film
What type of emulsion are ointments classified as?
Oil in Water (O/W)
What are the basic components of an emulsion?
- Oil phase
- Water phase
- Emulsifying agent/emulsifier
What are some common oils used for oral emulsions?
Liquid paraffin
Castor oil
Cod liver oil
Arachis oil
What are some common oils for IV emulsions?
Fatty acids are commonly used for emulsions intended for long-term parenteral use
ex. cottonseed oil, soya bean oil, and safflower oil
What are some commonly used oils in topical emulsions?
Turpentine oil
Benzyl-benzoate
Various oils as carriers for the active ingredient
What are fixed oils, and which ones are used commonly in emulsions?
Non-volatile/fatty oil of animal or plant derivation (mixtures of fatty acids, usually triglycerides)
Ex. castor oil, cod liver oil, olive oil (know these for the test)
Which essential oils are commonly used in emulsions?
Non fatty oils from plants
ex. mint oil, rose oil, peppermint oil
Which mineral oils are used in emulsions?
Mineral oils: a grade of liquid petrolatum
ex. liquid paraffin
What substances can be used for the water phase in emulsions?
Water*
Glycerol*
Propylene glycol*
Polyethylene glycols*
Sorbitol
Know all asterisked terms for exam
How do emulsifying agents stabilize emulsions?
Emulsifying agents concentrate at the oil/water interface and do the following to stabilize emulsions:
- Reduce interfacial tension
- Imparting a charge on the droplet (electrostatic repulsion)
What are the requirements for an excellent emulsifying agent?
- Molecular structure
- Stable interface
- Chemical stability
- Inertness
- Non-toxic, non-irritating
- Odorless, tasteless, colourless
- Not cost-prohibitive (improves accessibility)
What are the divisions of emulsifying agents based on their chemical structure?
- Synthetic and semi-synthetic
- Natural
- Finely dispersed solids
- Auxillary agents
What are the divisions of emulsifying agents based on their mechanism of action?
- Surface active agents
- Hydrophilic colloids
- Finely divided solid particles
What are some qualities of water-soluble emulsifying agents?
They favour o/w emulsions
3 classes (natural, cellulose derivatives, synthetics)
What are some qualities of anionic soft soaps?
Form o/w emulsions
Fatty acid + univalent cations
What are some qualities of anionic hard soaps?
Form w/o emulsions
fatty acid + multivalent emulsions
What are some qualities of cationic surfactants?
They are made from quarternary ammonium and, therefore are very hydrophilic
Not useful as emulsifiers, but have good antimicrobial activity
What are some qualities of finely divided solids?
They are made from hydrophilic inorganic solids (ex. calamine)
Large quantities can function as emulsifiers
Most support o/w emulsions, but some like bentonite can support w/o emulsions
What are some qualities of natural non-ionic surfactants?
They are auxiliary emulsions to stable o/w emulsions
Despite its lower emulsifying character, it is often used in formulations for patients that are allergic to other emulsifiers
What are some qualities of synthetic non-ionic surfactants?
They can be used in o/w and w/o emulsions
Heat and pH stable, can be used in high electrolyte concentration
ex. polysorbate 80
What are some qualities of zwitterionic emulsifiers?
Amphoteric (charge depends on pH of surrounding medium)
ex. PLO gel (lecithin-based gel)
Which sufactants are important to know for the exam?
- Anionic
- Cationic
- Non-ionic
- Zwitterionic
How do surfactants increase emulsion stability?
Surfactants reduce the force causing each liquid to resist mixing. This force is known as interfacial tension
What are the three types of interfacial films formed by emulsifying agents?
- Mono-molecular film
- Multi-molecular film
- Solid particle film
How do mono-molecular films stabilize emulsions?
The emulsifying agent moves toward the liquid:liquid interface and effectively reduced surface interfacial tension
How do multi-molecular fims stabilize emulsions?
Unlike mono-molecular, there is no change in interfacial tension
They instead form a protective sheath around droplets and impart a charge. This results in the droplets repelling each other, reducing the ability of the liquids to separate
How do solid particle films stabilize emulsions?
Forms particulate layer and starts to swell. This increases overall liquid viscosity, effectively slowing droplet movement
ex. finely divided solids
Do surfactants form micelles in aqueous solutions at any surfactant concentration?
No, initially they will be engaged in surface adsorption (surfactants on the surface of water)
Surfactants concentration has to pass a certain point known as the critical micelle concentration (CMC point) before micelles are formed
Do all surfactant monomers in the mixture form micelles after the CMC point?
No, although micelle form after the CMC point, some surfactant molecules remain engaged in surface adsorption
What is the aggregation number in the context of micelles?
This is the average number of surfactant monomers in a spherical micelle
What are some micelle characteristics in relation to the surfactant?
Non-ionic surfactants form micelles more readily compared to ionic surfactants
Micelles are in equilibrium with monomeric surfactant molecules in the emulsion
Diameter of micelle is dependent on geometry and length of surfactant
Are surfactants with low CMC points preferred in o/w emulsions?
No, these surfactants will form micelles before they can coat lipid particles and entrap lipid particles in the micelle
Surfactants with high CMC points will form micelles around lipid particles
What are mixed micelles?
These micelles are formed when more than one type of surfactant is used
Are hydrophillic emulsifiers preferred in o/w emulsions?
Yes, they are less likely to form micelles without the lipid particle entraped within
Why are lipophillic emulsifiers preferred in w/o emulsions?
They will not form micelles in the oil phase, but will form micelles around the aqueous droplets
What is the HLB system?
The HLB system assigns each surfactant an HLB number which reflects its relative polarity (hydrophillic or lipophillic)
Do lipophillic surfactants have low HLB numbers?
Yes, lipophillic surfactants have low HLB values (3-8). They are used in w/o emulsions
Hydrophillic surfactants have high HLB numbers (8-16). They are used in o/w emulsions
What is a common lipophillic surfactant?
Spans are sorbitan fatty acid esters and they have low HLB values from 1.6-8.6
What is a common hydrophillic surfactant?
Tweens are more hydrophillic derivatives of spans. They have high HLB values (10.5-16.7)
Is the oil phase incorporated into the liquid phase when forming a well-dispersed emulsion?
No, the water phase always goes into the oil phase slowly (both o/w & w/o emulsions)
What is the purpose of antioxidants in emulsions?
They are used to prevent auto-oxidation of oil and lipid components of the emulsion (rancidity)
ex. BHA, BHT
can be used in combination with chelating agents
What is the purpose of preservatives in emulsions?
They are used to prevent growth of micro-organisms (not a concern in most emulsions due to conservative BUDs (beyond use dates))
If used, lipid and water soluble preservatives are combined: methyparabens (water phase) and propylparabens (oil phase)
Know that parabens are a major class of preservatives
What are humectants?
They are compounds which are capable of absorbing water from the air
What is the purpose of humectants in emulsions?
These agents are used to reduce the evaporation of the water phase of emulsions (to prevent drying of the preparation)
If water phase volume decreased, drug concentration could increase, which could lead to accidentally administering a stronger dose than intended
What are the four main methods of emulsion formation?
- Dry Gum Method (Continental Method)
- Wet Gum Method (English Method)
- In situ Soap Formation
- Surfactant-based emulsions
If using acacia as a surfactant, what type of mortar should be used to crush it into a powder?
Use a porcelain mortar because it can bear high shear stress from crushing acacia into a fine powder
What is the product of mixing cottonseed oil and lime water?
They form a hard soap (anionic surfactant) via the in situ soap formation process.
What are the four main types of equipment used to make emulsions?
- Mechanical stirrers (good for low viscosity and large quantities)
- Homogenizers (most widely used, pressure is used to incorporate oil)
- Ultrasonifiers (use ultrasound waves to break down emulsified droplets, produces a uniform emulsion)
- Colloid Mills (used in industry applications)
What are some good label choices for emulsions?
- Shake well
- May or may not be refrigerated
- For external use only
What is the definition of a stable emulsion?
The dispersed droplets retain their original characteristics and remain uniformly distributed throughout the continuous phase
What are the three main threats to the physical stability of emulsions?
- Creaming or Sedimentation
- Flocculation
- Coalescence (breaking, cracking)
What occurs to dispersed droplets in an emulsion when creaming occurs?
Dispersed droplets can flocculate and move upwards in the emulsion column and will settle at the time given enough time
The speed of this process is determined by Stoke’s Law (refer to page 68)
negative values from Stoke’s Law show creaming
What occurs to dispersed droplets in an emulsion when sedimentation occurs?
Dispersed droplets can flocculate and move downwards in the emulsion column and will settle at the time given enough time
The speed of this process is determined by Stoke’s Law (refer to page 68)
positive values from Stoke’s Law show sedmentation
Do creaming and sedimentation increase the likelihood of coalescence occurring in emulsions?
Yes
Review Stoke’s Law on page 68
How can creaming and sedimentation be slowed?
Reduce droplet size (homogenization)
Increase viscosity of the continuous phase with hydrocolloids like methylcellulose
Reduce density difference between the two phases (not used in practice)
Are creaming/sedimentation reversible processes?
Yes, just shake the emulsion before administration
Review slide 73
What is coalescence in emulsions?
It is the complete fusion of droplets within an emulsion, which leads to a drop in the number of individual droplets, eventually causing the complete separation of the water and lipid phases
Is coalescence in emulsions a reversible process?
No, pharmacist has to remake compound
What factors prevent coalescence from occurring?
The presence of surfactants and hydrocolloids that form molecular films between the two phases in o/w emulsions
The presence of long hydrocarbon chains of surfactant molecules which project into the lipid phase
