Surfactants and Suspending Agents

Question 1

Why can insects walk on water?

Answer 1

Surface tension

Question 2

How is surface tension created>

Answer 2

-Water molecules are attracted to each other and like to stay together, especially on the surface where there is only air above
- hydrogen bonds pull down from the air = tension on surface

Question 3

surface tension problematic in pharamceutics

Answer 3

• Wetting process hindered if surface tension too high
• Add surfactant molecules to replace some of the water molecules in the surface
• Forces of attraction between surfactant and water molecules are less than those between two water molecules, hence the contraction force is reduced

Question 4

Surfactant

Answer 4

Surface
Active
Agent

Question 5

What is a surfactant?

Answer 5

• An amphiphilic/amphipathic molecule that consists of a distinct hydrophobic and hydrophilic region
• A molecule that accumulates at interfaces
• A molecule that aggregates or self-assembles

Question 6

Everyday applications of surfactants:

Answer 6

1. Paint (pigment dispersions)
2. ice cream (smooth texture - resistance to rapid meltdown)
3. Detol/washing up liquid (trap and remove dirt)

Question 7

Pharmaceutical applications of surfactants:

Answer 7

Surfactants are present in suspensions and emulsions
Aggregated surfactants can be used as drug delivery vehicles: e.g. micelles and vesicles to solubilise insoluble drugs

1. cetyl
2. myristyl alcohol (aveeno)
3. polyethylene glycol (pfizer injection)

Question 8

Phospholypid:

Answer 8

hydrophobic tail
hydrophilic head

Question 9

in water

Answer 9

face hydrophilic head

Question 10

in oil

Answer 10

face hydrophobic tail

Question 11

What lowers interfacial tension?

Answer 11

Adsorption at the oil-water

Question 12

Types of surfactants

Answer 12

1. ionic surfactants (anionic - dissociate at high pH/cationic - dissociate at low pH)
2. Non-ionic surfactants (less toxic and irritant than ionic - widely used)
3. Mixtures of surfactants (produce more stable emulsions)

Question 13

Classifications of surfactants - ANIONIC

Answer 13

-negatively charged surfactant, +ive couterion
-e.g sodium dodecyl sulfate

-soluble in water
-forms self-emulsifying bases with fatty alcohols
-detergent in medicated shampoos
-skin cleanser in topical applications

Question 14

Classification of surfactant - NOn-IONIC

Answer 14

-uncharged
-e.g ‘Brij’ - alkyl chain linked to polyoxyethylyne gycol
-spans = sorbitan acid esters

-tweens = polyoxethylene sorbitan fatty acid esters

Question 15

Classification of surfactants - MIXTURE

Answer 15

-Zwitterionic
-two charges, overall neutral

Question 16

Surfactants can be…

Answer 16

1. Drugs
2. Naturally occurring: Bile salts, Lecithin,Synovial fluid, Lungs surfactant

Question 17

Co-surfactants

Answer 17

• To achieve very low interfacial tension, a second amphiphile (co-surfactant) is incorporated

-Usually short chain alcohols or amines ranging from C4 to C10
- Helps in the formation and stabilisation of micelles/microemulsions
- Increases the flexibility and fluidity of the interface

Question 18

Co-surfactant mixture role =

Answer 18

covering the whole droplet of oil

Question 19

Surfactants/Co-surfacants > Classification> self-assesmby>

Answer 19

Micelles

Question 20

What is Micelles?

Answer 20

Molecular dynamics simulation of a micelle formed by non-ionic surfactants dissolved in water, with a hydrophobic core

Question 21

Micelles size and shape:

Answer 21

• Colloidal spherical or near spherical nanoparticles
• Loose aggregates of 50 – 100 surfactant molecules into a single entity
• Size of micelles ~ 5 – 10 nm

Question 22

Micelles are dynamic structures:

Answer 22

• Individual monomers may enter or leave the micelles = rapid process
• Micelles are constantly breaking down and reforming = slow process

Question 23

Surfactant self-assembly…

Answer 23

-60 randomly positioned molecules of polysorbate 80 first aggregate into small clusters, which then come together to form a single micelle

-The micelle then undergoes restructuring to yield its final equilibrium arrangement

Question 24

Micelle formation in water;

Answer 24

• Extensively hydrogen bonded
• “Flickering clusters”
• Highly ordered water molecules form “cages” around the hydrophobic alkyl chains

Question 25

Micelle formation in water - 3 examples

Answer 25

> Dispersion of lipids in water
-Each lipid molecule forces surrounding water molecules to become highly ordered
Clusters of lipid molecules
-Only lipid portions at the edge of the cluster force the ordering of water. Fewer water molecules are ordered, and entropy is increased
Micelles
-All hydrophobic groups are sequestered from water, no highly ordered shell of water molecules is present, and entropy is increased

Question 26

Thermodynamics of micelle formation in water:

Answer 26

1. The higher the entropy change, the more favourable the reaction, because the lower the free energy
2. Micelle formation results in an increase in entropy because water molecules regain their freedom upon micellization (i.e. loss of the cage structure)

Question 27

Thermodynamics

Answer 27

• The second law: The level of disorder (entropy) in the universe is steadily increasing
• Reaction favours lowest free energy state

Question 28

Interaction of water and hydrophilic head groups

Answer 28

> Water molecules interact with surfactant head groups
- Polyethylene glycol
- Carboxylate groups

Question 29

What stops micelles from growing?

Answer 29

Head groups start to repel each other if brought in too close in contact

Question 30

Ionic surfactants

Answer 30

CH3(CH2)11SO3Na
Strong repulsion - small micelles

Question 31

Non-ionic surfactants

Answer 31

CH3(CH2)11(OCH2CH2)12OH
Less strong repulsion - large micelles

Question 32

CMC

Answer 32

Critical micelle concentration

Question 33

What is CMC?

Answer 33

The surfactant concentration at and above which micelles are formed
Determined by measuring the surface tension at different [surfactants]

Question 34

Surface tension - CMC

Answer 34

Above the CMC, surface tension of the solution is constant

Question 35

Osmotic pressure

Answer 35

Osmotic pressure depends on the no. of molecules present in water, tailed off after CMC

Question 36

Conductivity

Answer 36

At CMC, this abruptly causes the concentration of the current carrier anions to decreases

Question 37

Light scattering

Answer 37

Intensity of scattered light between free surfactant monomers and micelles

Question 38

Drug solubilisation

Answer 38

Micellar solubilisation only occurs above the CMC

Question 39

Applications of micelles

Answer 39

• Micellar solubilisation
• Process whereby a material insoluble in water (e.g. a poorly soluble drug) can increase its ‘apparent’ solubility by being incorporated into a micelle (dissolve in the hydrophobic environment of the micelle)

Question 40

Examples of micelles - daily use

Answer 40

• Micelles water (makeup remover)
  -shampoo (micelles shampoo)

Question 41

Micelles in pharamcy:

Answer 41

Colloidal formulation - ‘Konakion MM’

Question 42

Site of solubilisation

Answer 42

a) Hydrocarbon core : non-plar solubilistate
b) Core/mantle region : amphiliphilic solubilsate
c)Headgroup (mantle) region : more polar solubilisate
d) Surface adsorption : Polar solubilisate on the shell

Question 43

Suspending agents

Answer 43

• Micellar solubilisation
• Process whereby a material insoluble in water (e.g. a poorly soluble drug) can increase its ‘apparent’ solubility by being incorporated into a micelle (dissolve in the hydrophobic environment of the micelle)

Question 44

Ideal suspending agent

Answer 44

> Readily and uniformly incorporated into formulation
Readily dispersed in water without special techniques
Ensure the formation of a loosely packed system which does not cake
Does not influence the dissolution rate or absorption rate of the drug
Be inert, non-toxic and free from incompatibilities