PH2107 - suspension, colloids & nanoparticles 3 Flashcards
What are the two possible outcomes for particles when they collide?
- rebound
- associate
What are the two states of particles when they associate after a collision?
- temporary
- permanent
What happens when particles become associated with each other after a collision?
Clumps increase in overall size and may sediment
- at which point the system may become impossible to re-disperse
What determines whether particles rebound and stay separated after collisions, or get permanently attached when they collide?
The balance of attractive and repulsive forces
What is of great importance in the stability of disperse systems?
Charge
How do particle surfaces acquire an electrical charge?
- Particle charge by differential ion dissolution
- Particle charge by ionisation
- Particle charge by ion adsorption
What property do different ions have?
Different solubilities
- silver ions (Ag+) are more soluble in water than iodide ions (I-)
How does differential ion dissolution work?
Adding silver iodide to water, the more soluble silver (Ag+) would dissolve into the bulk of the water faster, leaving behind iodide ions (I-)
Remaining particle surface therefore acquires an overall negative charge
How can the molecules at the surface of a structure become charged?
If a particle is comprised of molecule/moieties that can be ionised
What is particle charge by ionisation influenced by?
By the pKa of the ionisable groups
- can be manipulated by adjusting the pH of the dispersant / continuous phase
How can a surface charge of a structure be aquired?
By the adsorption of ions onto the surface of an electrically neutral particle
- i.e. if more anions adsorb to a surface, the surface of the particle will develop a net negative charge
Which charge is more often gained in water?
In water, surfaces tend more often to become negatively charged than positively charged
Why does the surface of water more often tend to become negatively charged?
- cations are generally more hydrated than anions so more favourable for them to stay in the water phase
- this leaves anions which are more likely to adsorb onto the particle surface
What charge must a disperse system have?
It must be electrically neutral overall
What influences the distribution of ions in the rest of the volume of liquid in a disperse system?
The surface charge of the particles
What forms around each charged particle in a disperse system?
Distinct layers
What is an EDL?
Electrical Double Layer
What are the three distinct regions of an electrical double layer?
- inner region - includes charged surface and adsorbed ions
- diffuse region - beyond adsorbed ions and up to the edge of the electrically neutral region
- electrically neutral region - bulk solvent, outside the EDL
How many distinct regions make up an electrical double layer?
Three
What is a stern layer?
A monolayer of ions adsorbed onto particle surface
What is a stern plane?
The boundary between the tightly bound stern layer and diffuse layer
What is the diffuse layer?
Contains molecules loosely bound to the stern layer, extending to a distance
- debye length
What is the shear plane?
An imaginary line through the middle of the diffuse layer
What is the electrical double layer (EDL)?
Comprised of stern layer and diffuse layer
What is the electroneutral region (ENR)?
Non-attracted bulk solvent molecules throughout the continuous phase up to the EDL of the next particle
What is the DeBye length?
The distance between Stern layer and EDL limit
- the thickness of the exponential region of the plot
What is k dependent on in a charged system?
k is a constant that varies between systems which is dependent on the electrolyte concentration of the liquid phase
- adding electrolyte (increasing ionic strength) increases k and therefore decreases 1/k and that means that the thickness of the EDL is decreased
What does the EDL theory show?
There is an uneven distribution of ions in a disperse system
What is an electrical potential?
A difference in charge between two areas
What is an electrical potential measured against?
The bulk ENR
What is the relationship between distance from the surface and electrical potential?
Potential decreases with the distance from the surface
- drops rapidly and linearly between particle surface and the Stern plane
- then has a more gradual, exponential decrease towards zero
Why does the electrical potential decrease with distance from the surface?
The counterions close to the surface act as a screen to other ions
- reduces the attraction between the charged surface and the counterions further into the bulk solution
What is the Nerst potential (E)?
The potential between the true solution and the electroneutral region of the solution
What is the Stern potential?
The potential between the Stern plane and the ENR
What is the zeta potential?
The charge at the Shear plane, measured in mV
- quantities the degree of repulsion between similarly charged particles and the likely (in)stability
- hence the fundamental determinant in stability determinations
What varies between formulations and can be manipulated to achieve stability?
Zeta potential
What are the zeta determinations?
- the closer the zeta potential to zero, the greater the tendency to floc
- the higher the zeta potential, the more stable the system
- for a dispersion to remain stable, the zeta potential should be either > +30 mV or < -30 mV
What are the two type of particle-particle interactions in disperse systems?
- attractive interactions (VA)
- repulsive interactions (VR)
What causes attractive interactions (VA)?
Van der Waals (vdW) forces between molecules in the surface layers of the interacting particles
How can the strength of Van der Waals forces be measured?
de Boer and Hamaker calculated the attractive forces between spheres of the same radius
VA = -Aa/12H
Attractive Interactions (VA)
A Hamaker constant
a particle radius
H distance between particles
What is the relationship between the attractive force and distance?
The attraction decreases as the distance increases
What causes repulsive interactions (VR)?
Electrical charges on the surfaces of particles, due to
- adsorption of charged polymers or surfactants at the interface
- polarity differences between the solid and the liquid
- ionisation of chemical groups at the surface of the particles
- adsorption of small inorganic ions onto particle surfaces
Where do repulsive interactions act?
Over approximately the thickness of the double layer
What is the relationship between distance between particles and repulsive force?
VR decreases with distance between particles, more sharply than van der Waals, VA
What does DVLO stand for?
Derjaguin and Landau, and Verwey and Overbeek
What is DVLO?
The interaction between two particles (VT) in terms of van der Waals attractive forces (VA) and electrical repulsive forces (VR)
VT = VA + VR
What happens as particles approach each other?rs
They will come under the attractive influence of van der Waals forces, which will be opposed by the repulsive forces of overlapping diffuse layers
What regions are there between two particles?
Four distinct regions between two particles
- primary minimum
- primary maximum
- secondary minimum
- secondary maximum
What happens at primary minimum?
- VA predominates at very low H i.e. when particles are close togther
- irreversible aggregation occurs - particles clump together to form compact flocs and become sufficiently heavy to settle
Undesirable in a formulation!
What happens at primary maximum?
- occurs within the EDL - the repulsive forces act as an energy barrier to aggregation and particles remain separate from each other
- after settling, they can be hard to re-disperse
Undesirable in a formulation!
When does primary maximum occur?
At intermediate distances (within the thickness of the electrical double layer) due to a high VR. The height (i.e. degree of repulsion) depends on the VR and therefore surface and zeta potential
What happens at secondary minimum?
- an open loose structure develops and the particles remain suspended
- any flocs and partial flocs are large and can usually be broken up by shaking
Desirable for a formulation!
When does secondary minimum occur?
At large H because, even though the VA decreases with distance, VR decreases even more sharply. The depth of the trough on the graph depends on particle size
What happens at secondary maximum?
- an open loose structure develops and the particles remain suspended
- flocs cannot form
Desirable state for a pharmaceutical
What are the three states of aggregation (groupings of particles)?
Full flocculation (irreversible) Deflocculation Partial flocculation (reversible)
What is full flocculation?
- primary minimum phenomenon
- particles settle very quickly
- irreversible
- particles are closely aggregated
- some continuous phase vehicle is trapped, reducing the amount of free vehicle and making the formulation very viscous and difficult to pour
- a single large aggregate is formed on standing
- shaking may be enough to deform the aggregate but it is very difficult or impossible to redisperse (i.e. it is clayed)
What is deflocculation?
- primary maximum phenomenon
- particles remain separate
- particles are small so settle slowly (Stoke’s Law)
- VR allow particles to ‘slide’ or ‘slip’ past each other as they sediment
- these characteristics prevent liquid being trapped in sediment
- compact sediments of low sedimentation volume are produced (caked)
- sediment does not easily redisperse on shaking
What is flocculation in terms of particles?
- secondary minimum phenomenon
- formation of loose aggregates (groups) of particles which constantly break up and reform
- aggregates are relatively large so sedimentation is rapid
- liquid is trapped within and between aggregates
- sediment has a high sedimentation volume
- shaking can re-disperse the sediment and a homogenous system may be obtained
What is sedimentation volume determination, F?
The ratio of the ultimate volume to the original volume
When does sedimentation volume determination arise > 1?
When networks of flocs so loose and fluffy that they expand, and so ultimate volume > the original volume
F=Vu/Vo
Vu=equilibrium volume of sediment
Vo=Total volume of suspension
Which patients may need to be prescribed an oral liquid medicine?
Patients who are unable to swallow oral solids easily
Patients who require a dose which is difficult to deliver accurately through available solid oral dosage forms
Also in certain patients / conditions where a faster onset of action is required vs. solid oral form
