Week 8 disperse systems surfactants and suspending agents Flashcards
Surface tension
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
Surfactant
Surfactant – Surface Active Agent
A surfactant molecule is:
-An amphiphilic/ amphipahic molecule that consists of a distinct hydrophobic and hydrophilic region
-A molecule that accumulates at interfaces - can arrange themselves to have hydrophilic heads facing the aqueous region and hydrophobic tails away from (in oil for e.g.,)
-A molecule that aggregates or self-assembles
-If there are enough surfavtants they can arrange themselves into a spherical structure - known as micelle
Pharmaceutical applications - 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
To stabilise the water within the oil / oil within the oil e.g., creams / ointments
Some drugs need to be stabilised in lipid nanoparticles
Arrangements of amphipahtic molecules
Micelle - hydrophilic head points towards aqueous and hydrophobic tail towards the oil
Reverse micelle - Same arrangement but the other way around
How 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
Ionic surfactants
Surfactants that have a charge
-Anionic (dissociate at high pH)
-Cationic (dissociate at low pH)
Non-ionic surfactants
Widely used, less toxic and irritant than ionic surfactants
Mixtures of surfactants
To make nicer micelles, a combination of ionic and non-ionic surfactants is used
-Produce more stable emulsions
Classification of surfactants : Anionic
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
Classification of surfactants : Cationic
Positively charged surfactant, negative counterion;
Cetylpyridinium chloride (quaternaryammonium/ pyridinium)
-Freely soluble in water
-Has antimicrobial activity – cleaning of wounds, contaminated utensils,
preservative
-> Bacterial cell membrane is made of lipids, the positive charge can disturb the cell membrane of the bacteria so they can no longer survive
-Enhance transdermal drug delivery preparations
Classification of surfactants : Non-ionic
Uncharged, still have the hydrophobic hydrocarbon chain and the hydrophilic side that likes water, has lots of oxygen even though uncharged
-Spans = Sorbitan fatty acid
esters
-Tweens/Polysorbates =
Polyoxyethylene sorbitan fatty
acid esters
Classification of surfactants : Zwitterionic
Two charges in the same molecule, overall neutral (net charge is 0)
Surfactants other forms
-Drugs: Surfactants can be drugs themselves
-Naturally occurring;
-Bile salts -> helps to emulsify fats we ingest
-Lecithin
-Synovial fluid
-Lungs surfactant
Co-surfactants
To surround an oil droplet for example we can use a mixturfe on ionic and non-ionic surfacts however, there may still be gaps in between them -> therefore we use co-surfactants
Co-surfactants;
-Accompany the main surfactant
-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-surfactants 2
-The surfactant/cosurfactant mixture is able to form an efficiently packed film, covering the whole droplet
-Produces an excellent emulsion
-If you do not have the optimal number of surfactant and co-surfactant molecules, it will produce a poor emulsion as it cannot form a nicer micellar shape that will effectivley en compass the oil
Pharmaceutical surfactant and co-surfactant mixtures
Pharmaceutical companies produce mixtures that have the surfactants and co-surfactants in the right amounts for us
Micelles - How surfactants form micelles
-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 - dyanamic process, once they are formed they do not permanently stay formed they can form and break;
->Individual monomers may enter or leave the micelles = rapid process
->Micelles are constantly breaking down and reforming = slow process
Surfactant self-assembly
E.g.,
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
Critical packing parameter
Determines when there are enough surfactants in a micelle
Dependent on the;
-Volume of the hydrocarbon chain, V
-Length of the hydrocarbon chain, lc
-Cross sectional area of the hydrocarbon chain, a
Micelle formation in water
Water:
-Extensively hydrogen bonded
-“Flickering clusters”
-Highly ordered water molecules form “cages” around the hydrophobic alkyl chains
Dispersion of lipids in water
If you have multiple surfactants in the water -> a monolayer
Each lipid molecule forces surrounding water molecules to become highly ordered
Clusters of lipid molecules: only lipid molecules at the edge of the cluster force the ordering of water -> fewer water molecules are ordered, entropy is increased
Dispersion of lipids in water 2
With more surfactants they form the micelle,
All hydrophobic groups are sequestered (remove all the water so that only oil remains inside) from water, no highly ordered shell of water molecules is present, and entropy is increased
Core of the micelles will be oil
Thermodynamics of micelle formation in water
Thermodynamics
-The second law: The level of disorder (entropy) in the universe is steadily increasing
-Reaction favours lowest free energy state
Micelle formation results in an increase in entropy because water molecules regain their freedom upon micellization - due to loss of “cage” structure
When free energy is negative the reaction will be highly favorable
Interaction of water and hydrophilic head groups
Water molecules interact with
surfactant headgroups
Head groups start to repel each
other if brought in too close in
contact -> stops micelles from
growing
Ionic surfactants are smaller as the heads repel eachother stronger than in non-ionic surfactants
Critical micelle concentration (CMC)
When micelles are being formed
-The surfactant concentration at and above which micelles are
formed
-Determined by measuring the surface tension at different surfactants
CMC
When you add sjurfactants the surface tension is reduced
At the point where the surface tension becomes constant (CMC) we know the micelles have been formed
At CMC they form the monolayer and beyond the CMC miceller structures start to form, the monolayer is still there but miceller structures are forming
Osmotic pressure
