Lecture 9: Lipid Based Drug Delivery Systems Flashcards
What is a coarse dispersion?
- droplet sizes > 200 nm
- unstable
- scatter light resulting in opaque appearance
- can be seen under light microscopy
What are the two types of systems that can be formed with an oil, water and surfactant mixture?
Coarse dispersion and colloids
What is a colloidal system?
- Drop size < 200 nm
- do not scatter light so appear transparent
- can only be seen under electron microscope
What is an example of a coarse dispersion?
Macroemulsion - normal emulsion
What is an example of a colloidal system?
Microemulsions
Liquid crystals
Liposomes
SEDDS and SMEDDS
What are microemulsions?
They are a thermodynamically stable, transparent or translucent system with the dispersed droplet sizes < 200nm.
They are either
O/w
W/o
Bicontinuous
What are the components of microemulsions?
- Water
- Oil
- Surfactant
- Co-surfactant
What oils are used in microemulsions?
Mineral oils,
Vegetable oils
Tri and di glycerides
Fatty acid esters
What surfactants are used in microemulsions?
Non-ionic
Zwitterionic
Anionic and cationic are less commonly used
What co surfactants are used in microemulsions?
Short and medium chain alcohols
What are the general advantages of microemulsions ?
- ease of preparation
- clarity
- long term stability
- ability to be filtered
- vehicle for drugs of different lipophilicities
- low viscosity
What are the general disadvantages of microemulsions?
-biological incompatibility of surfactant and/or co surfactants used such as cationic, anionic surfactants, short chain alcohols etc.
What are the specific advantages of w/o microemulsions?
- protection of water soluble drugs
- sustained release of water soluble drugs
- increased bioavailability
What are the specific advantages of o/w microemulsions?
- increased solubility of lipophilic drugs
- increased bioavailability
What are the specific advantages of a bicontinuous microemulsion?
Promising for topical (epidermal and ocular) drug delivery due to good spreading and wetting properties to skin
How is a microemulsion prepared?
By first constructing a pseudo-ternary phase diagram to determine the amount of each component to add.
This varies depending on the properties of each ingredient
Different quantities can result in different types of colloidal systems, hence the formulation is made, and via visual observations, phase contrast and polarising light microscopy, we can determine what sort of colloidal system has been formed and plot a pseudo-ternary phase diagram.
What sort of tests are used in the physical chemical characterisation of microemulsionS?
- Visual examination for phase separation
- Phase contrast and polarised light microscopy
- Freeze fracture transmission electron microscopy
- Electrical conductivity measurements
- Viscosity measurements
- Dye solubilisation
- Stability
- In vitro release study
How can visual examination for phase separation characterise a ME?
ME should be transparent,
If the product is cloudy, it indicates that either phase separation has occurred, or the product is actually a liquid crystalline system or a coarse emulsion
How can phase contrast polarised light microscopy characterise a ME?
Under a microscope, the dispersed phase and the dispersion medium can be seen. A coarse emulsion will appear to have equal distribution of droplets and size of droplets whereas an unstable emulsion will show droplets of multiple different sizes
A polarised microscope can also show birefringence exhibited by liquid crystals. This would not be apparent in a ME
How can freeze fracture transmission electron microscopy characterise a ME?
Can observe microemulsion droplets in fine detail and check they are in the <200nm range
How can electrical conductivity experiments help to characterise a ME?
If a ME sample conducts well this indicates the external phase is water.
A bicontinuous ME will also exhibit high conductance
How can viscosity measurements help to characterise a ME?
All ME systems exhibit Newtonian flow
An increase in oil weight ratio decreases viscosity and a lower viscosity is desireable for drug delivery and pharmaceutical development
A ME has a lower viscosity than a LC
What are liposomes?
Vesicles that are made up of one or more lipid bilayers surrounding the internal aqueous compartment
The most common used lipid is the phospholipid which forms the backbone of the bilayer
What are the 5 main groups of phospholipids that are available that can be used for liposome preparation?
1) phospholipids from natural sources
2) phospholipid modified from natural sources
3) semi-synthetic phospholipid
4) fully synthetic phospholipid
5) phospholipid with non-natural head groups