Flashcards in Emulsion and Suspension Stability (1) Forces that Govern Stability Deck (35)
What is a liquid in liquid colloid?
What is a solid in liquid colloid?
What are emulsions and their properties?
Dispersion of liquid in a second immiscible liquid (oil/water or water/oil)
Require an emulsifier for stability
Produced by homogenisation - input of energy
What prevents phase separation in emulsions?
Molecular film of emulsifier at the interface
What happens to energy when unimxed oil and water becomes a dispersed emulsion
Dispersed emulsion has a higher energy than the unmixed oil and water
What would happen to an emulsion without emulsifiers?
Seperate back into the original low energy system
How do surfactants maintain separation?
The charged layer formed by surfactant at the interface repels similar charges
Where in practice would you use emulsions?
IV - total parental nutrition administration of fats (soya bean oil and medium chain triglycerides) intralipids
*Fat absorbed from GI tract circulates as chylomicrons; feeding emulsions try to simulate these droplets
Administration of hydrophobic drugs
Oral - feeding of fats via enteric feeds
oral delivery of hydrophobic drugs
Intramuscular w/o emulsions for sustained release
Emulsion vaccine adjuvants
What kinda emulsifiers are acceptable?
Phospholipids from egg yolk or soya beans
Some of the hydrophillic Pluronics (F68) (F127)
More scope in small volume parenterals e.g. polysorbate, bile salts
What kind of log P does a hydrophobic oil-soluble drug have?
High log P
How are hydrophobic oil soluble drugs incorporated into an emulsion?
Dissolved in oil and then emulsified, drug must be very hydrophobic or the drug will transfer through the aqueous phase and crystallise out
What are surface active drugs like?
Possess hydrophobic and hydrophillic parts, can be absorbed at the interface
More difficult to formulate due to solubility problems
-can solubilise the drug in emulsifier solution and then use this to emulsify the oil phase
What is a Diprivan injection?
Propofol is the most widely used drug for IV anaesthesia
The drug is very hydrophobic and so is dissolved in soya-bean oil
The oil is dispersed in isotonic water carrier to form an emulsion
150nm oil droplet size, if it increased it could be life threatening to the patient e.g. if it aggregates!
What is flocculation?
Particles/droplets cluster together in an open structure, maintain their individual identity
Can be redispersed into a single phase by shaking so the particles are no longer aggregated
Sometimes flocculation is desirable in a formulation
What is coagulation and or aggregation?
Small aggregates form
Surface area is decreased so surface tension is experienced by fewer molecules
Attractive forces between particles very strong
Cannot be redispersed to single particles by shaking
Permanent failure of medicine
What is coalescence or cracking?
Droplet structure lost entirely and impossible to reform emulsion in clinic
Total failure of the medication
What is Brownian Motion and what particles are affected?
Particles less than about 2 microns diameter are constantly moving due to BM
What factors affect the kinetic energy of the particles?
Temperature and external forces e.g. shaking
What happens as particles approach one another?
Forces of electrostatic repulsion interation = Vr
Forces of attraction due to VDW forces = Va
-steric forces (due to overlapping electrons and the associated energy cost when atoms move too closely together) if they have non-ionic surfactant on their surfaces =Vs
These energies combine to form Vt
What is Vt
What is the DVLO theory?
Theory of balance between electrostatic repulsion and attractive forces
In the case of charged particles what parts of the Vt equations must be consider?
Va and Vr (not Vs as we only consider steric forces when they have a non-ionic surfactant)
What does a potential diagram show?
A graph of the force against particle seperation
Va changes as a function of what?
1/H (H being particle separation)
As the particles get closer (so H decreases) Va increases
With Va attractive forces at big seperations what happens?
There is still a small attractive force
There's a sharp increase in the force of attraction at close proximity of particles
What causes the charge in a suspension (repulsive forces)?
Most coilloidal particles are charged
The source of the charge in a suspension is
-ion dissolution; ionic substances e.g. drugs acquire charge by uneven dissolution of oppositley charged ions. If more cations dissolve then the solution becomes negatively charged
-ion adsorption e.g. surfactants
Why is it complex / harder to determine repulsive forces than attractive forces for example?
most colloids formed with water as the liquid phase and this means that electrolytes are found in the water e.g. H+, Na+, K+, MG2+, CA2+ and OH-
These ions will be attracted to or repelled from the charged surface of the colloid particle of drug and thus form what is known as an electrical double layer
Electrostatic repulsive forces / energy Vr as a result of the interactions of the electrical double layer
What order in a diagram from left to right are the potentials shown
Surface potential -> Stern potential -> Zeta potential
What happens to Vr (repulsive forces) at close proximity of the atoms?
Does not increase sharply at close separations
Repulsive force reaches zero when the particle separation reaches a certain limit (nothing to repel them further)