Surfactants and Suspending Agents Flashcards
Why can insects walk on water?
Surface tension
How is surface tension created>
-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
surface tension problematic in pharamceutics
- 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
Surfactant
Surface
Active
Agent
What is a surfactant?
- 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
Everyday applications of surfactants:
- Paint (pigment dispersions)
- ice cream (smooth texture - resistance to rapid meltdown)
- Detol/washing up liquid (trap and remove dirt)
Pharmaceutical applications of surfactants:
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
- cetyl
- myristyl alcohol (aveeno)
- polyethylene glycol (pfizer injection)
Phospholypid:
hydrophobic tail
hydrophilic head
in water
face hydrophilic head
in oil
face hydrophobic tail
What lowers interfacial tension?
Adsorption at the oil-water
Types of surfactants
- ionic surfactants (anionic - dissociate at high pH/cationic - dissociate at low pH)
- Non-ionic surfactants (less toxic and irritant than ionic - widely used)
- Mixtures of surfactants (produce more stable emulsions)
Classifications of surfactants - ANIONIC
-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
Classification of surfactant - NOn-IONIC
-uncharged
-e.g ‘Brij’ - alkyl chain linked to polyoxyethylyne gycol
-spans = sorbitan acid esters
-tweens = polyoxethylene sorbitan fatty acid esters
Classification of surfactants - MIXTURE
-Zwitterionic
-two charges, overall neutral
Surfactants can be…
- Drugs
- Naturally occurring: Bile salts, Lecithin,Synovial fluid, Lungs surfactant
Co-surfactants
- 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
Co-surfactant mixture role =
covering the whole droplet of oil
Surfactants/Co-surfacants > Classification> self-assesmby>
Micelles
What is Micelles?
Molecular dynamics simulation of a micelle formed by non-ionic surfactants dissolved in water, with a hydrophobic core
Micelles size and shape:
- Colloidal spherical or near spherical nanoparticles
- Loose aggregates of 50 – 100 surfactant molecules into a single entity
- Size of micelles ~ 5 – 10 nm
Micelles are dynamic structures:
- Individual monomers may enter or leave the micelles = rapid process
- Micelles are constantly breaking down and reforming = slow process
Surfactant self-assembly…
-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
Micelle formation in water;
- Extensively hydrogen bonded
- “Flickering clusters”
- Highly ordered water molecules form “cages” around the hydrophobic alkyl chains
Micelle formation in water - 3 examples
> 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
Thermodynamics of micelle formation in water:
- The higher the entropy change, the more favourable the reaction, because the lower the free energy
- Micelle formation results in an increase in entropy because water molecules regain their freedom upon micellization (i.e. loss of the cage structure)
Thermodynamics
- The second law: The level of disorder (entropy) in the universe is steadily increasing
- Reaction favours lowest free energy state
Interaction of water and hydrophilic head groups
> Water molecules interact with surfactant head groups
- Polyethylene glycol
- Carboxylate groups
What stops micelles from growing?
Head groups start to repel each other if brought in too close in contact
Ionic surfactants
CH3(CH2)11SO3Na
Strong repulsion - small micelles
Non-ionic surfactants
CH3(CH2)11(OCH2CH2)12OH
Less strong repulsion - large micelles
CMC
Critical micelle concentration
What is CMC?
The surfactant concentration at and above which micelles are formed
Determined by measuring the surface tension at different [surfactants]
Surface tension - CMC
Above the CMC, surface tension of the solution is constant
Osmotic pressure
Osmotic pressure depends on the no. of molecules present in water, tailed off after CMC
Conductivity
At CMC, this abruptly causes the concentration of the current carrier anions to decreases
Light scattering
Intensity of scattered light between free surfactant monomers and micelles
Drug solubilisation
Micellar solubilisation only occurs above the CMC
Applications of micelles
- 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)
Examples of micelles - daily use
- Micelles water (makeup remover)
-shampoo (micelles shampoo)
Micelles in pharamcy:
Colloidal formulation - ‘Konakion MM’
Site of solubilisation
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
Suspending agents
- 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)
Ideal suspending agent
> 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
