Define an emulsion
A two phase system in which one phase is dispersed as fine liquid droplets into another phase.
What are types and examples of coarse emulsions?
- oil in water: milk
- water in oil: butter
- multiple emulsions
What is the pharmaceutical relevance of emulsions?
Lipophlic drugs can be entrapped in aqueous medium in a dissolved form. This allows for predicatable behaviour as the dissolution step is bypassed, and gives improved bioavailability.
How can drug release behaviour of emulsions be altered?
By using the distribution and partition coefficients of drugs, sustained release can be acheived.
What are oral, topical and parenteral applications of emulsions and chracteristics of each?
oral:
- easy to swallow and taste-making is possible
- usually oil in water as this has low viscosity
Topical:
- ointments (water in oil); more viscous and occlusive, drug release can be slowed.
- creams (oil in water); good emollient properties and easier to spread and wash off
- pseudo-plasticity and thixotropy are important in these for ease of administration.
Parenteral route:
- emulsions can be injected via IM or IV
- IV must be oil in water in order to be compatible with blood
- IM release rate can be altered by using a viscous, oily vehicle
- multiple emulsions can allow for sustained release of oily drug from an oily vehicle.
How are emulsions prepared?
Prepared by mixture of oil and aqueous phase liquids in the presence of emulsifiers. Emulsifiers can be; - surfactants - colloidal carbohydrates - colloidal solids - high molecular weight alcohols - protein substances
Give surfactant types, and examples
Ionic surfactants are charged, and examples are sodium lauryl sulfate (SLS) and cetrimide.
Non-ionic surfactants are not charged, an example is Tween 20.
Describe how hydrophilic colloids work as emulsifiers, and give examples.
Hydrophilic colloids form a film around the internal phase globule, and slows down coalescence by the presence of a mechanical hydrophilic barrier between oil and water.
There is a increase in the viscosity of the dispersion medium (stoke’s law) and electrostatic repulsion occurs if the particles have ionisable groups.
Examples are acacia and tragacanth.
Describe the relative toxicity of emulsifiers and give examples where appropriate.
Relative toxicity is
non-ionic < anionic < cationic.
Cationic is the most toxic due to the negative charge of membranes, where these will interact with membranes.
e.g. cetrimide used for topical preparations to penetrate the skin.
For parenteral use, non-ionic surfactants should be used e.g. tween 20.
Briefly describe factors influencing emulsion stability and define each factor.
A stable emulsion will not be flocculated or cream, and must not show coalescence or breaking.
- Flocculation: aggregation of dispersed droplets into clusters due to attraction of forces.
- creaming: due to density differences there will be a region with higher concentration of disperse phase than the other. Oil phase will be the top layer.
- Coalescence: Dispersed phase droplets flow together to gain energy and surfactant layer at the interface is broken down.
- breaking: complete phase seperation.
How can flocculation be prevented?
Charge repulsion can prevent flocculation, which can be acheived by having a high charge density in the dispersed phase. Addition of electrolytes and charged emulsifiers can be used - however we need to be weary of toxicity.
How can creaming be prevented?
By stoke’s law, creaming can be prevented by;
- reduction of droplet size in internal phase to a certain limity (surface energy)
- increase in the viscosity of the internal phase
- reduction of density between two phases (difficult to alter)
How can coalescence be prevented?
- reduction of interfacial tension by surfactant
- presence of mechanical barrier (hydrocolloid)
- droplets with high charge density (repulsion)
Give 5 approaches to stabilise an emulsion
- Mechanical barrier
- Introducing charge
- Reducing interfacial tension
- Reduced particle size (balance increase ST)
- Increase viscosity
What formulation additives are commonly used in emulsions and why?
- buffers; chemical stability and tonicity control to ensure physiological compatibility
- density modifiers to reduce creaming
- antioxidants to prevent oxidation of oil
- flavours, colours, perfumes, sweeteners
How are emulsions used in total parenteral nutrition?
Continous diffusion of essential nutrients for patients who are unable to use their digestive tract. Administered directly to their blood stream and tailored specifically to their needs.
Contains fat and water soluble components including sugars, amino acids, fats, electrolytes, vitamins etc.
What are characteristics of micro emulsions?
- thermodynamically stable
- optically isotropic
- transparent
- 10-200nm droplet size
- forms spontaneously
- low viscosity
- can be used for sustained release
- can increase drug F
What are considerations to be made when using mciroemulsions?
Microemulsions have a very high SA:V ratio. More surfactant is needed to coat this larger effective SA. Surfactants are toxic at high concentrations - so non-ionic surfactants can be used or cosolvents can be used.
