Colloids Flashcards
What drug delivery systems employ colloidal systems?
- Hydrogels
- Microparticles
- Emulsions
- Liposomes
- Micelles
- Nanoparticles/Nanocrystals
Colloids Definition
- Particles < 0.5 um dispersed in another phase
- Liposomes, nanoparticles, dendrimers…
- It is now recognized that nano-sized drug delivery systems may have significantly improved performance (i.e. treating cancer)
What particle size range is in colloidal systems?
- 10 A - 5000 A
- 1A = 10^8 cm = 10^-10 m = 0.1 nm
- 1nm - 500nm (0.5 um)
What does a small particle size mean?
A small particle size means a large interfacial area and a system in which interfacial properties are important.
dG = surface tension x area
Characteristics of Colloids
- Large SA
- Drive to decrease surface free energy
- Tendency for aggregation
- Unequal distribution of phases - tendency to move to top or bottom
Surface Area
- A cube w/1 cm edge has a volume of 1 cm^3 and surface area of 6 cm^2
- If the material in the cube is subdivided into smaller cubes having an edge of 100um: 1) volume stays the same. 2) SA is 600,000 cm^2 (↑ 105 fold)
- Surface phenomena are critical for colloidal systems
3 Types of Colloids
1) Lyophilic
2) Lyophobic
3) Association
1) Lyophilic Colloids
- Strong and extensive interactions between dispersed phase and dispersion medium
- Thermodynamically stable systems
- I.e. gelatin in water, solution of chromosomal DNA
2) Lyophobic Colloids
- Thermodynamically unstable systems
- Little interaction between dispersed phase and dispersion medium (low adhesional forces)
- I.e. inorganic particles in water, charcoal in water
3) Association Colloids
- Thermodynamically stable systems
- The dispersed phase consists of aggregates of amphiphilic molecules or ions (i.e. micelles)
- At low concentration, these molecules exist in true solution
- At high concentration, they aggregate to form micelles (CMC)
3 Types of Colloidal Properties
1) Optical
2) Kinetic
3) Electrical
1) Optical Properties
- Cannot see them using a light microscope
- Faraday-Tyndall Effect: light may be absorbed, scattered, polarized or reflected by the dispersed phase of a colloid
2) Kinetic Properties
- Brownian Movement: particles are generally small enough to be influenced by the collision with molecules of the dispersion medium
- When particles are observed, they are seen to move in a random, erratic manner
Consequences of Brownian motion
- Stable colloids are systems in which the dispersed particles do not settle, because the force of gravity is counteracted by Brownian movement
- Colloids will diffuse from a region of high concentration to a region of low concentration
- Fick’s Law of Diffusion
Fick’s Law
- dq = amount of substance
- dt = time
- S = plane of area
- dc = change of concentration
- dx = distance travelled
- D = diffusion coefficient
Stokes-Einstein Equation
- k = Boltzman constant
- T - absolute temperature
- n = viscosity of solution
- R = hydrodynamic radius of the particle
D = kT/6πnR
What is the effect of INCREASING PARTICLE SIZE on the rate of diffusion of a colloid?
D = kT/6πnR
Decreases rate of diffusion
What is the effect of INCREASING TEMPERATURE on the rate of diffusion of a colloid?
D = kT/6πnR
Increases rate of diffusion
What is the effect of INCREASING VISCOSITY OF THE DISPERSION MEDIUM on the rate of diffusion of a colloid?
D = kT/6πnR
Decreases rate of diffusion
3) Electrical Properties
- Interface in contact with an aqueous phase usually acquires a charge
- Ionization of surface acidic or basic groups
- Adsorption of dissolved ions and polymers
What are cations ions in solution called?
Counterions
What are anions in solution called?
Similions
Bulk Solution
Electrically neutral - equal concentration of similions and counterions
Diffuse Layer
- “Adsorbed” ions on the surface of the colloid
- Diffuse layer with an excess of counterions to neutralize surface charge
- Surface charge: -7
- Net charge in the diffuse layer: +7
Double Diffuse Layer
Electrically neutralizes the particle surface charge
Zeta Potential
- THE HIGHER THE # THE MORE STABLE
- Measures the voltage difference between the double diffuse layer and the neutral region of the solution
- Measures the degree of attraction and repulsion between adjacent particles
- Agglomeration of colloids/suspensions
- Stability of colloids/suspensions
Surface Tension
The amount of energy required (similions) or released (counterions) when an ion is moved from bulk into contact with the surface
Physical Stability
- Frequent collision between colloidal particles (Brownian Motion)
- Irreversible destruction (Coagulation/coalescence)
- Temporary aggregation (flocculation)
- Electrical and molecular forces
What are 2 predominant forces that act between colloidal properties?
1) Van der Waals attractive forces
2) Electrostatic repulsive forces
1) Van der Waals forces
- Dependent on: (1) the size of particles and (2) distance between particles
2) Electrostatic repulsive forces
- Dependent on: (1) surface charge of particle and (2) thickness of the electrical double layer, diffuse layer
Coagulation
Attractive forces overwhelm repulsive forces
Aggregation
Collection of colloids into groups
Coagulation/Coalescence
Colloids are closely aggregated and difficult to redisperse (particles are at the primary minimum on the energy curve)
Flocculation
Aggregates that have an open structure and where the particles remain a small distance apart (secondary minimum)
How are colloids unstable? And how do you stabilize them?
- Colloids are unstable with respect to forming an aggregate
- To stabilize: (1) Electrostatic stabilization and (2) Steric stabilization
1) Electrostatic stabilization
- Particles repel each other due to surface charges
- Lyophobic solutions are stabilized using this method
2) Steric stabilization
Polymers absorbed to the surface make it difficult for particles to approach each other
Electrical Properties of Lyophobic Colloids
Generally, the larger the diffuse double layer the greater the repulsive force and the more stable the colloid
Extent of the Double Diffuse Layer
1/K = “thickness of the DDL”
- Increasing concentration of electrolyte decreases 1/K and leads to coagulation
Effect of Electrolyte Valence on DDL
Polyvalent counterions will have a much more significant effect on the thickness of the DDL than monovalent ions
Double Layer Theory
Addition of polyvalent counterions results in compression of the diffuse double layer
Steric Stabilization
- Use of macromolecules to stabilize lyophobic colloids
- Adsorb to particle surface
- Prevent colloids from approaching each other sterically
Polymer Bridging
- Polymer bridging occurs when a polymer promotes an opposite effect that occurs in steric stabilization
- Thus, instead of stabilization of the particles, the polymer promotes flocculation
What makes adsorbed polymers to either stabilize or bridge colloidal systems?
- Bridging happens at very low polymer concentration
- In steric stabilization, due to high polymer concentration, the polymer covers all or most of the particle surface
Electrostatic Stabilization
Combination of both steric and electrostatic stabilization
Micelles
Aggregates of amphiphilic molecules
Critical Micelle Concentration (cmc)
Concentration of amphiphiles above which micelles begin to form
Affect of Association Colloids on SURFACE TENSION
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Affect of Association Colloids on SOLUBILITY
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Hydrogels
- Gel = colloid with liquid as dispersion medium and solid as dispersed phase
- Hydrogel = water is the dispersion medium
- Natural and synthetic (gelatin and polyethylene glycol hydrogels)
- Wound healing, tissue engineering, drug delivery systems (responsive to environment (pH, temp, etc), sustained release, biocompatible and degradable)
Microparticles
- 0.2 - 5 um microspheres loaded with drug
- Polymers
- Carriers for vaccines, chemotherapeutics
- Improve release profiles
- Targeting
Emulsions
- O/W emulsion: oil is discontinuous phase and water is continuous phase (vice versa)
Liposomes
- Consist of outer membrane(s) and an inner liquid core
- Can be loaded with drugs/excipients
- Lipophilic drugs associate with membrane
- Hydrophilic drugs associate with inner core
Micelles
- Similar to liposomes but do not have inner liquid structures
- Used as microcontainers for poorly soluble hydrophobic drugs
- Surface can be modified (like liposomes)
Nanoparticles
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