Emulsion and Suspension Stability (1) Forces that Govern Stability

Question 1

What is a liquid in liquid colloid?

Answer 1

Emulsion

Question 2

What is a solid in liquid colloid?

Answer 2

Suspension

Question 3

What are emulsions and their properties?

Answer 3

Dispersion of liquid in a second immiscible liquid (oil/water or water/oil)
Require an emulsifier for stability
Produced by homogenisation - input of energy

Question 4

What prevents phase separation in emulsions?

Answer 4

Molecular film of emulsifier at the interface

Question 5

What happens to energy when unimxed oil and water becomes a dispersed emulsion

Answer 5

Dispersed emulsion has a higher energy than the unmixed oil and water

Question 6

What would happen to an emulsion without emulsifiers?

Answer 6

Seperate back into the original low energy system

Question 7

How do surfactants maintain separation?

Answer 7

The charged layer formed by surfactant at the interface repels similar charges

Question 8

Where in practice would you use emulsions?

Answer 8

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

Question 9

What kinda emulsifiers are acceptable?

Answer 9

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

Question 10

What kind of log P does a hydrophobic oil-soluble drug have?

Answer 10

High log P

Question 11

How are hydrophobic oil soluble drugs incorporated into an emulsion?

Answer 11

Dissolved in oil and then emulsified, drug must be very hydrophobic or the drug will transfer through the aqueous phase and crystallise out

Question 12

What are surface active drugs like?

Answer 12

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

Question 13

What is a Diprivan injection?

Answer 13

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!

Question 14

What is flocculation?

Answer 14

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

Question 15

What is coagulation and or aggregation?

Answer 15

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

Question 16

What is coalescence or cracking?

Answer 16

Droplet structure lost entirely and impossible to reform emulsion in clinic
Total failure of the medication

Question 17

What is Brownian Motion and what particles are affected?

Answer 17

Particles less than about 2 microns diameter are constantly moving due to BM

Question 18

What factors affect the kinetic energy of the particles?

Answer 18

Temperature and external forces e.g. shaking

Question 19

What happens as particles approach one another?

Answer 19

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

Question 20

What is Vt

Answer 20

Va+Vs+Vr

Question 21

What is the DVLO theory?

Answer 21

Theory of balance between electrostatic repulsion and attractive forces

Question 22

In the case of charged particles what parts of the Vt equations must be consider?

Answer 22

Va and Vr (not Vs as we only consider steric forces when they have a non-ionic surfactant)

Question 23

What does a potential diagram show?

Answer 23

A graph of the force against particle seperation

Question 24

Va changes as a function of what?

Answer 24

1/H (H being particle separation)

As the particles get closer (so H decreases) Va increases

Question 25

With Va attractive forces at big seperations what happens?

Answer 25

There is still a small attractive force

There’s a sharp increase in the force of attraction at close proximity of particles

Question 26

What causes the charge in a suspension (repulsive forces)?

Answer 26

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

Question 27

Why is it complex / harder to determine repulsive forces than attractive forces for example?

Answer 27

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

Question 28

What order in a diagram from left to right are the potentials shown

Answer 28

Surface potential -> Stern potential -> Zeta potential

Question 29

What happens to Vr (repulsive forces) at close proximity of the atoms?

Answer 29

Does not increase sharply at close separations

Repulsive force reaches zero when the particle separation reaches a certain limit (nothing to repel them further)

Question 30

What is the primary maximum?

Answer 30

The peak of repulsive forces that is a barrier to aggregation

Question 31

What is the secondary minimum?

Answer 31

The stage at which forces of attraction between particles is weak and causes flocculation

Question 32

What is the primary minimum?

Answer 32

Permanent aggregation of particles because the really close together, forces of attraction are maximal and forces of repulsion are low

Question 33

What affect does high kinetic energy have on the potential diagram?

Answer 33

Primary maximum is insufficient to stop particle

RESULT - COAGULATION

Question 34

What affect does low kinetic energy have on potential diagram?

Answer 34

Primary maximum too great a barrier
Particle has insufficient energy to continue its path towards neighbouring particle
Particle also has insufficient energy to escape the secondary minimum

RESULT- FLOCCULATION

Question 35

What affect does intermediate kinetic energy have on potential diagram?

Answer 35

Primary maximum too great a barrier
Particle has insufficient energy to continue its path toward neighbouring particle
Particle also escapes secondary minimum (BM)

RESULT - STABLE COLLOIDAL FORMULATION