surfactants and suspending agents Flashcards
How is surface tensionn problematic in pharmaceutics?
- 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
What is a surfactant molecule?
- 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
What are some 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
How do surfactants work?
- Adsorption at the oil-water interface lowers interfacial tension
- Aids the dispersal of the oil into droplets of a small size
- Maintains the particles in a dispersed state
What are the two types of surfactants?
- ionic surfactants
- non ionic surfactants
What are some properties of ionic surfactants?
- Anionic (dissociate at high pH) and
cationic (dissociate at low pH)
What are some properties of non-ionic surfactants?
- Widely used, less toxic and irritant
than ionic surfactants
What happens if you mix the two types of surfactants?
- Produce more stable emulsions
What are the classification of surfactants?
*anionic
*cationic
*non-ionic
*zwitterionic
What are the properties of anionic surfactants?
negatively charged surfactant, positive counterion
* Sodium dodecyl sulfate (SDS) (aka sodium lauryl sulfate, SLS)
* Freely soluble in water
* Forms self-emulsifying bases with fatty alcohols
* Detergent in medicated shampoos
* Skin cleanser in topical applications
What are some properties of cationic surfactants?
positively charged surfactant, negative counterion
* Cetylpyridinium chloride (quaternary ammonium/pyridinium)
* Freely soluble in water
* Has antimicrobial activity – cleaning of wounds, contaminated utensils,
preservative
* Enhance transdermal drug delivery preparations
What are some properties of nonionic surfactants pt2?
*uncharged
* spans = sorbitan fatty acid esters
* tweens/polysorbates = polyoxyethylene sorbitan fatty acid esters
What are zwitterionic surfactants?
- two charges
- overall neutral
What other types of surfactants are there?
*drugs
*naturally occuring:
- bile salts
- lecithin
- synovial fluid
- lungs surfactant
What do co-surfactants do?
- Helps in the formation and stabilisation of micelles/microemulsions
- Increases the flexibility and fluidity of the interface
- covers entire water droplet
What are the 3 types of co-surfactant/ surfactant mixture?
- cetrimide emulsifying wax
- emulsifying wax
- non-ionic emulsifying wax
What are micelles?
- Colloidal spherical or near spherical nanoparticles
- Loose aggregates of 50 – 100 surfactant molecules into a single entity
- Size of micelles ~ 5 – 10 nm
What are some properties of micelles?
- Micelles are dynamic structures
- Individual monomers may enter or leave the micelles = rapid process
- Micelles are constantly breaking down and reforming = slow process
Describe surfactant self assembly with micelles?
- 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
Describe micelle formation in water in terms of dispersion of lipids in water, clusters of lipid molecules
+ micelle
- 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
What are the thermodynamics like in micelle formtion of water?
Micelle formation results in an increase in
entropy because water molecules regain
their freedom upon micellization (i.e. loss of
the cage structure)
How does water interact with hydrophilic head groups?
- Water molecules interact with
surfactant headgroups - Polyethylene glycol
- Carboxylate groups
- Head groups start to repel each other
if brought in too close in contact →
stops micelles from growing
How does repulsive forces differ between non ionic surfactant head groups and ionic surfactant head groups?
ionic: strong repulsion = small micelles
non ionic: less strong repulsion = large micelles
What is CMC?
- critical micelle concentration
- The surfactant concentration at and above which micelles are formed
- Determined by measuring the surface tension at different [surfactants]
What is the surface tension like above the CMC?
- the surface tension of the solution above the CMC is constant
What is osmotic pressure like for the CMC?
- Osmotic pressure depends on the no. of molecules present in water, tailed
off after CMC
What is conductivity like with the CMC?
- At CMC, this abruptly causes the concentration of the current carrier
anions to decreases
What is light scattering like (CMC)?
- Intensity of scattered light between free surfactant monomers and
micelles
(above CMC)
What is drug solubilisation like (cmc)?
- Micellar solubilisation only occurs above the CMC
What is an application 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)
What are the sites of solubilisation?
Several possible sites of solubilisation:
a) Hydrocarbon core
* Non-polar solubilisate
b) Core/mantle region
* Amphiphilic solubilisate
c) Head group (mantle) region
* More polar solubilisate
d) Surface adsorption
* Polar solubilisate on the shell
What are suspending agents for?
- To reduce the rate of settling of suspended active ingredients
- Increases the viscosity of the suspension
- Drugs can be readily and uniformly resuspended before use
What are some examples of suspending agents?
- Polysorbate
- Methylcellulose
- Povidone
- Xanthan gum
- Carbomer
What is the 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
