Colloids review questions Flashcards
Define disperse systems and their two main components
disperse system = system in where one substance (the disperse phase) is dispersed or distributed as particles [more or less uniformly] throughout another phase (the dispersion medium or continuous phase).
Identify disperse systems based on the combination of their components’ states of matter and name each combination.
* cn be in solid, liq or gas, of the 9 possibilities 8 are colloidal dispersons
(gas in gas = molecular dispersion)
Classify and describe dispersion based on their particle size
Molecular dispersions (true dispersions; i.e. SOLUTIONS, size \< 1nm) Colloidal dispersions (particle size of 1 nm - 1μm) Fine and coarse dispersions (particle size \> 1 μm)
What is the size range for colloidal dispersions?
1-1000 nm
Define sol and gel as colloidal dispersions.
sol = dispersions of solids in liquid
Some colloidal dispersions under the proper conditions of concentration and temperature set to a solid or semi-solid ⇒ gels.
difference between true solutions and colloidal dispersions
True solutions contain molecules, typically <1 nm
Colloidal dispersions contain particles > 1 nm < 1000nm
*some cases such as with macromolecules (proteins, polymers, nucleic acids) while they are molecular solutions they are also considered colloids due to the size of the molecules that can range approximately 1-20 nm
three main types of colloidal systems?
Lyophobic (hydrophobic) Colloids
Lyophilic (hydrophilic) Colloids
Association Colloids
Compare lyophobic and lyophilic colloidal particles:
solvation, thermodynamic stability, redispersibility, preparation method/formation, sensitivity to electrolytes.
lyophobic:
- the degree of attraction is small or non-existent
- often unstable
- particles aggregating rather than remaining in contact with the dispersion medium
Lyophilic
- dom by repulsion
- disperse phase interacts appreciably with the dispersion medium
- affinity exists between the dispersed particles and the dispersion medium. This contributes to the stability of the system.
Gibbs free energy is defined as ∆G= ∆H-T∆S. How is this equation used to explain formation of lyophobic and lyophilic colloids.
Lyophobic
- little/no attraction, thermodynamically unstable so particles aggregate to lower surface free energy
- irreversible systems
- ∆G positive, ∆H positive
- Surface free energy NOT lowered by solvation; reverse process (agglomeration) spontaneous
Lyophillic
- thermodynamically stable and reversible
- ∆G = neg, ∆H = typically neg
- surface free enrgy lowered by solvation
- no floculation of coagulation
What are the two main methods for preparing lyophobic colloids? What is the main factor playing a role in stabilizing lyophobic particles?
Lyophobic colloids are formed by either dispersion or condensation
- Dispersion – mechanical disintegration or by addition of deflocculating agents (also called peptization)
- Condensation – physical and chemical
examples for lyophobic systems and formulations.
- water or aqueous solutions: water-insoluble drugs, clays (kaolin), colloidal sulfur, metal (colloidal gold, colloidal iron)
- Aurothioglucose colloidal dispersion, Iron Dextran Injection, Colloidal Sulfur topical preparation
. What types of lyophilic systems exist? What is the main factor playing a role in stabilizing lyophilic particles?
Two major classes:
- Water soluble polymers – size of individual molecules are colloidal in dimension
- Particulate dispersions – highly solvated
Stabilizing forces: hydration layer (main), electrical double layer (if applicable)
Give examples for lyophilic systems and formulations.
True Solutions
- water soluble polymers, acacia, povidone, protein solutions
Gelled Solutions
- high concentration of polymers
- e.g. gelatin or starch → set to gels on cooling
- methylcellulose → gels on heating
Particulate Dispersions
- contain solid particles, such as bentonite or microcrystalline cellulose
Define association colloids.
micelles - contain both large lyophobic moieties with strongly lyophilic groups within the same molecule and orient themselves accordingly in the solution.
What is ‘amphipatic’?
Lyophilic and lyophobic portions within the same molecule
Why is particle size an important consideration in dispersion stability?
Particle size is important in many ways, among these are
- Influence on sedimentation rate
- Increase in surface free energy and aggregation tendency
Explain how surface free energy is related to particle size and the stability of the system. Based on the equation ∆ F = γ ∆A
Essential characteristic common to all disperse systems; as particles become smaller, surface area to volume ratio becomes larger;
what are the ways to lower surface free energy in a dispersion. Will decreasing surface free energy improve the physical stability of the dispersion?
decrease surface free energy are decreasing the interfacial tension and/or decreasing the surface are
. Note that to keep the particles small (with larger surface area) decreasing the interfacial tension is the main choice.
Define the kinetic properties of colloidal particles.
Brownian motion, Diffusion and Sedimentation
Explain the principle of Fick’s law of diffusion and how the different parameters influence the rate of diffusion.
What is meant by concentration gradient and how this concept is used in formulation.
- concentration gradient: existence of high concentration region and a low concentration region
- directs the movement of molecules/particles
- By maintaining ‘sink conditions’ the highest concentration gradient will provide continuous movement of molecules/particles.
Stokes law describes the sedimentation properties of particles. Explain the role of the different parameters in the context of formulation stability.
. Describe the Tyndall effect and how it can be utilized for measuring particle size.
A beam of light directed at a colloidal sol will be scattered or absorbed.
The scattering of light makes the sol appear turbid *Tyndall effect
The degree of light scattering is proportional to particle size and can be used for measurements
Can you observe colloidal particles by light microscope or by electron microscope? Explain.
Generally no,
colloidal particles are too small to be seen with an optical microscope (resolution is about 0.5 μm),
the high resolving power of electron microscopy must be employed where resolution is about 1 nm.
Explain the concept of electrical double layer and its role in particle stability.
- charge onparticle surface will attract oppositely charged ions (counter ions) to achieve electrical neutrality: this causes the formation of an electrical double layer around the particle
- electrical double layer determines the distance between adjacent particles in the dispersion ⇒ directly affects the stability of the system.
Name the parts of the electrical double layer (A-D), region E and potentials defined at different distances from the particle surface (1-3).
A – surface of particle
B – tightly bound layer
C – shear plane
D – diffuse part of double layer; layer with excess counter ions or also called Gouy- Chapman layer
E- electro-neutral region; bulk solution
1- surface potential
2- Stern potential
3- zeta potential
Define shear plane and zeta potential.
Shear plane= boundary after the tightly bound layer marking the the mobile portion of the double layer
potential measure at the shear plane = zeta potential
How does the electrical potential change as we move away from the particle surface?
- Zeta potential decreases linearly from the surface potential to the Stern potential
- decays exponentially thereafter and becomes zero at the end of the double layer
How the Debye length influences the interaction between lyophobic particles?
Debye length is the length of the double layer and 2X the Debye length (two particles)
indicates the distance between particles
Define deflocculated and flocculated particles and the zeta potential in each of these systems.
Deflocculated: particles remain dispersed; characterized by a high ζ potential
Flocculated: particles form loose aggregates (flocs); characterized by low ζ potential
If zeta potential is high the colloidal soltion is thermodynamically stable or unstable
stable
Is it important to lower the zeta potential to achieve a pharmaceutically stable colloidal sol? Why?
Yes, lowering zeta potential provides a flocculated dispersion that is considered redispersible, hence pharmaceutically stable
What is the difference between ‘colloidally stable’ and ‘pharmaceutically stable’ dispersions.
What are the practical implications for formulation stability?
deflocculated systems = colloidally stable due to electrostatic repulsion between particles -> NOT pharmaceutically stable due to caking (not redispersible) after sedimentation had occurred
- harmaceutically stable system is the one that can be easily redispersed, therefore a flocculated system (not colloidally stable) should be used.
Explain the effect of added counterions on the zeta potential of colloidal particles.
Added counterions lower the zeta potential.
Define DLVO theory and the presence and balance of attractive and repulsive forces around colloidal particles.
a) name the axes (D,E,F) of the graph
b) explain curves VA, VR and VT
D – repulsive potential
E – attractive potential
F – distance between particles
VA – van der Waals attraction
VR – electrostatic repulsion
VT – total energy of interaction
explain the forces responsible for the potential minimum and maximum
A, B and C
what is the relationship between the balance of these forces and the physical stability of the particles?
A – primary minimum: attraction predominates - coagulation
B - secondary minimum – slight attraction predominates – flocculation
C – primary maximum – repulsive forces predominate due to the electrical double layer
The balance of these forces determine whether the particles will be individually dispersed or aggregate (either loosely or irreversibly).
Explain the difference between flocculation, aggregation and coagulation.
terms represent the degree of binding of the particles from loose to irreversible.
- Flocculated and aggregated particles can still be redispersed but coagulated particles cannot.
Define ‘caking’. Which colloidal system is prone to caking? Why?
An irreversible form of sedimented particles; deflocculated systems are prone to caking because as particles eventually sediment coagulation occurs due to compaction.
Provide examples for flocculating agents and their mechanism of action.
Electrolytes – decrease zeta potential
Lyophilic macromolecules – protective colloid effect; eg Polymers – provide steric hindrance
Define sedimentation volume ratio (F) and how it changes in relation to zeta potential.
F=Vu/Vo
Vu final volume of sediment
Vo total volume of the suspension
*Lowering zeta potential results in increased F
What are protective colloids and what types are used in pharmaceutical formulation?
Lyophilic macromolecules can be added to lyophobic colloids to act as ‘protective colloids’
- adsorb onto other particle surfaces preventing close contact of particles and therefore preventing coagulation
What is coacervation and microencapsulation and how is it used in drug delivery?
Coacervation = precipitation of colloid particles from solution/dispersion with the addition of electrolytes or non-solvents
- when done in the presence of drug particles the colloid particles coat the drug particles – microencapsulation.
used to prepare slow and controlled release dosage forms.
Give several examples for pharmaceutical applications of colloids
- Delivery systems: Micelles, microemulsions, liposomes, microspheres, nanoparticles, and drug – polymer conjugates, nanocrystals
– Radioactive Colloids: Diagnostic and therapeutic agents in nuclear medicine
- Excipients: emulsifier, stabilizer, viscosity modifier, suspending agent
