Colloids and Suspensions Flashcards
What is a dispersed system?
A system in which one component is dispersed as particles or droplets throughout another component
Colloidal dispersions
Dispersions in which the size of the dispersed
Liquid aerosol
e.g. cloud
Dispersed phase - liquid
Continuous phase - gas
Solid aerosol
e.g. smoke
Dispersed phase - solid
Continuous phase - gas
Foam
e.g. bath foam
Dispersed phase - gas
Continuous phase - liquid
Emulsion
e.g. milk
Dispersed and continuous phase - liquid
Suspension
e.g. calamine lotion
Dispersed - solid
Continuous - liquid
Solid emulsion
e.g. ice cream
Dispersed - liquid
Continuous - solid
Colloids VS suspensions
- In a colloid, we have particles of a drug - aggregates consisting of many drug molecules
- In a pharmaceutical suspension the particle size is generally >1μm
- This is different to a colloidal system, where particle size is <1μm by definition
But the principles of colloidal science apply to pharmaceutical suspensions
Why do we use suspensions?
- Poorly soluble drugs cannot always be made into solution
- For taste making - unpleasant tastes may be less noticeable in a suspension
- Drug may be more stable if formulated as a suspension instead of a solution
e.g. OTC: calamine lotion, Kaolin mixture, amoxicillin suspensions
What makes a good suspension?
- Must be easy to disperse upon shaking - redispersibility
- Small particles of the same size - ensures patients don’t find it gritty
- Homogenous, need to be evenly distributed for uniform dosing
Adding particles to a clear liquid changes how the light is…
absorbed, transmitted, and scattered by the liquid
The Tyndall Effect
- If a beam of light is passed through a true solution, there is very little scattering of the light, and so the path of the beam cannot be seen
- In a colloid, the particles scatter the beam of light so you can see its path
- Therefore, colloidal systems can be assessed based on how a beam of light behaves when it comes into contact with the system
- The less light that passes through the sample, the more turbid it is - and the greater the concentration of the dispersed phase
Motion in colloids
- Motion is a kinetic property
- In colloids, the particles are small <1μm
- This means they undergo Brownian motion - there will be a random movement of the dispersed particles throughout the continuous phase
Brownian motion
- Consider a solid-in-liquid colloid
- Irregular and complicated zigzag pattern
- Random collisions with:
- Solvent molecules
- Other particles
- Container wall
Diffusion in colloids
Fick’s First Law
dm/dt = -DA (dc/dx)
dm / dt = mass diffusing over time;
D = diffusion coefficient
A = area across which diffusion occurs
x = distance travelled
dC/dx = conc gradient (c1-c2/x1-x2)
Sedimentations
Stokes’ Law
(Look at notes)
The sediment ratio (order)
- Clarified zone
- Discrete particle setting
- Hindered setting
- Transition zone
- Compression
- Sediment
Sediment ratio = volume of sediment layer / total suspension volume
Quick fire
- Definitions of colloids and pharmaceutical suspensions
- Benefits of using a suspension over other dosage forms
- Optical and kinetic properties of a suspension
- Characteristics of a good suspension
- Process of sedimentation
How do we make a pharmaceutical suspension?
- Drug must have small particles of uniform size
- If the drug is water-insoluble, we may add a wetting agent. This breaks the interfacial tension, ensuring the solid particles disperse easily throughout the liquid
- Interfacial tension is an energy barrier which prevents the liquid spreading around the solid
Low VS high interfacial tension
- Low interfacial tension: the liquid spreads around the particle -> good suspension
- High interfacial tension: liquid does not spread around the particle -> bad suspension
Wetting agents
- Surfactants
- Hydrophilic colloids
- Simple solvents
- Increased wetting of hydrophobic particles leads to a decrease in surface tension
- Also decrease adsorption of particles to the container by applying a repellent coating to the particles in the suspension
- Without a wetting agent, particles tend to cling to the container
Determining if a substance is flocculated or deflocculated
- Deflocculated, where the particles remain as separate units
○ In a deflocculated system, the rate of sedimentation depends on the particle size, but general is slow
○ A slow rate of settling prevents liquid entrapment in the sediment, which becomes compact- Flocculated, where the particles exist as loose aggregates
○ Aggregates settle quickly, leads to liquid entrapment in the sediment, which tends to be fairly easy to redisperse
- Flocculated, where the particles exist as loose aggregates
Flocculated system characteristics
- Loose aggregates of particles
- Large volume of final sediment
- Rapid sedimentation rate
- Suspension clears quickly
- Entrapment of liquid within sediment
- Easy to redisperse sediment
Deflocculated systems
- Particles exist as discrete units
- Small volume of final sediment
- Slow sedimentation rate
- Suspension remains cloudy for a prolonged period of time
- Liquid entrapment in the sediment is prevented
- Difficult to redisperse
Aggregation
Collection of particles into groupsC
How does coagulation arise?
When the particles are closely aggregated and difficult to redisperse
In flocculation, aggregates have a loose structure, in which the particles are a small distance apart, only weakly bound into groups
Caking
Formation of a densely pack, non-dispersible, aggregate at the bottom of the container in a suspension
Viscosity enhancing agents
- If we increase viscosity of the liquid phase, the rate of sedimentation is reduced
- Materials may be added to a suspension with the aim of increasing viscosity
- Examples:
○ Polysaccharides
○ Celluloses
○ Hydrated silicates
○ Carbomers and silicon dioxide
Although sedimentation is delayed, it is not stopped
Flocculating agents
- Minimise extent of caking in a suspension
- Ideally we want a partially deflocculated system
- Examples:
○ Electrolytes
○ Surfactants
○ Polymers
○Carbomers or silicates
Electrical properties of colloids
- Occurrence of coagulation and / or flocculation is driven by electrical forces
- Particles tend to have a surface charge
- In water, this is typically a negative charge
- Lots of electrostatic interactions between a particle and the other components in the colloidal system
- The negative charge at the particle surface will attract positive ions in solution which in turn will attract negative ions ->results in the electrical double layer
How do the forces work
- All the particles in a pharmaceutical suspension are made up of the same drug – so they have the same charge
- We know that like charges repel – so these particles repel one another (VR).
But, there are also some attractive forces (VA). These arise from van der Waals interactions:
DLVO Theory
Vt = Va + Vr
t - total potential energy of interaction
a - potential energy of attractions
r - potential energy of repulsion
At a negative surface:
Electric Double Layer (EDL)
Surface Charge
The solid surface develops a net charge.
This attracts counter-ions from the surrounding solution.
Stern Layer (red)
A layer of ions strongly bound to the surface.
This forms the inner region of the electric double layer.
Diffuse Layer
Ions are more loosely associated with the surface.
They extend further into the solution, forming the outer region.
Shear Plane (red)
A virtual boundary within the diffuse layer.
Defines where the liquid begins to flow relative to the surface.
Zeta potential is measured here.
When the particles are close together…
attractive forces dominate and we get an energy minimum
At intermediate distances
double layers repel and give and energy minimum
An increase in electrolytes will…
- Increase the Debye-Huckel parameter (K)
- Decrease the thickness of the electric double layer (1/K)
- Decrease zeta potential
- Increase the depth of the secondary minimum
- Leading to: flocculation
Caking example with bismuth subnitrate and adding pottasium phosphate
- Bismuth subnitrate have a positively charged surface
- Initially, substance is deflocculated
- Adding KH2PO4 causes a reducing in zeta potential of the particles, because the particles adsorb phosphate anions
- As more KH2PO4 is added, the zeta-potential reduces to zero and then turns negative
- To obtain a flocculated non-caking suspension, need to control the zeta potential by adding the correct amount of electrolyte
Polymers in deflocculation
- Chemical groups in the polymer interact with the surfaces of the particles
- The free end of the polymer attaches to another particle, this gives interparticle bridging leading to flocculations
- If there are no other particles to interact with, the free end of the polymer coats the particle leading to restabilisation and a deflocculated system
- Need to carefully control the polymer conc.
Overall summary:
- A colloid is a dispersed phase in which the size of the dispersed particles in the continuous phase is in the range of 10-9 – 10-6 m
- Technically, a pharmaceutical suspension is not a colloid, because the particles are too big - but the principles of colloid science still apply
- The particles in a colloid move rapidly and randomly
- The particles in a colloid scatter light, leading to the Tyndall effect
- The electrical properties of a colloid determine it’s stability
- Pharmaceutical suspensions are a powerful type of formulation which can be applied against a range of diseases, overcoming a number of challenges associated with solutions
- A “good” suspension should contain small and evenly sized particles of drug, disperses a liquid carrier. The suspension must be redispersible upon shaking
- All suspensions will sediment over time. The rate at which they do so can be controlled through e.g. changing the viscosity of the liquid medium
- But, ultimately for a deflocculated system the formation of a dense, permanently bound “cake” will result - this needs to be avoided during the shelf life of the medicine
The only way to prevent caking is through using flocculating agents
