W10.2_Colloids and Excipients Flashcards
Give some pharmacological and biological examples of colloids.
- Pharmacological examples: emulsions, suspensions, aerosols (dispersed phase in dispersed medium)
- Biological examples: microorganisms suspensions, cells in culture
Compare the characteristics and examples of lyophilic and lyophobic colloids. What would be the dispersion and condensation methods to form a colloid?
- Lyophilic colloids: high affinity for dispersed medium causes spontaneous formation of colloid
- Water as medium = hydrophilic
- ex. natural polymers (acacia, tragacanth, methylcellulose) and proteins (albumin)
- Lyophobic colloids: low affinity for dispersed medium causes energy to be required in preparation to break large particles into fine ones and aggregate them
- Water as medium = hydrophobic
- Dispersion methods: colloidal mill (high shear dispersion between static cone and rotor), ultrasonic treatment (dispersing through regions to cavitate and compress medium)
- Condensation methods: formed from supersaturated solution usually by chemical reactions
Explain the properties of colloids regarding uniformity, shape, viscosity, motion, and colour.
- Usually polydisperse (different sizes/weight) -> use average size/molecular weight
- In different shapes (ex. spherical, ellipsoid, discs, rods, coils)
- High viscosity usually for lyophilic colloids (vice versa)
- Brownian motion affected by large particles (less diffusion of particles)
- Light diffraction used to determine size/molecular weight (Tyndall effect: the limit of light wavelength causes colloids to show colour, but only slightly in suspensions and none in solution)
Explain how ion dissolution happens in colloids and how it causes ion adsorption. Regarding the potential graph, explain what would happen to the ions under and over the surface of shear. How can the particles be separated? Define the thickness of electrical double layer (DBL) from the graph.
- Most surfaces have electrical charges when in contact with aqueous medium -> ion dissolution (unequal distribution of oppositely charged ions causes charges of ionic substances)
- Ion adsorption: net surface charge acquired by unequal adsorption of oppositely charged ions
- Under surface of shear (ζ): bound to interface
- Over surface of shear: more counter-ions than ions but are still free to move
- Particles can be separated by charge/size through electrophoresis
- 1/κ: thickness of DBL (electrical double layer) /Debye-Hückel parameter (between ψ(δ) and zero potential)
Regarding the physical stability of colloids, what could Brownian motion lead to? Explain the factors affecting physical stability of lyophobic and lyophilic systems (2/1).
- Brownian motion could lead to coagulation, aggregation, flocculated particles, dispersed particles
- Factors affecting lyophobic systems: electrical forces of repulsion, forces of attraction
- Factors affecting lyophilic systems: solvation
In lyophobic systems, explain the DLVO theory and describe the combined line of total poential energy in a graph.
- DLVO theory: using only repulsive and attractive forces assumptively to predict colloidal stability in lyophobic systems
- +ve: repulsive forces (electrostatic forces)
- -ve: attractive forces (van der Waals’ forces)
- Combined line of total potential energy of interaction (V(p)) between colloids
In relation to the DLVO theory, explain how the position of primary maximum and secondary minimum could influence the physical stability of colloids. Expain how adding excess electrolytes to the colloid could cause instability.
- Primary maximum > thermal energy: stable system
- Primary maximum < thermal energy: unstable as close contact would cause irreversibly bounding -> coagulation/ precipitation
- Secondary minimum < thermal energy: particles always repel each other -> no close contact
- Secondary minimum being moderately deep: systems give rise to loose -> easily reversible flocculation (important for emulsions and suspensions)
- Adding excess electrolytes: compresses double layer -> reduces repulsion forces -> reduces primary maximum -> instability
Explain how the physical stability of lyophilic system can be affected by macromolecules, electrolytes, polymers, and Stoke’s law.
- Solution of macromolecules use a combination of electric double layer interaction and solvation
- Both weakened significantly -> aggregation (still be soluble when no DBL interaction)
- Unaffected by small amount of electrolytes
- High amount of electrolytes: water of solvation lost -> salting-out effects
- Steric stabilisation: polymer materials (gums/non-ionic surfactants/methylcellulose) adsorb on surface -> stabilise lyophobic solutions in absence of significant ζ -> steric interaction causes repulsion
- Entropic stabilisation (loss of hydration in hydrated polymer chains)
- Application of Stoke’s law (size/density/viscosity) could affect stability (consequences: creaming, caking, sedimentation)
Define polymers and describe the properties of polymers.
- Macromolecules made of repetitive monomers
- Can be natural or synthetic, can be charged (polyelectrolytes)
- Flexible, polydisperse in length, semi-crystalline, can be star-shaped/branched/linear
- Water soluble polymers can attract water by increasing viscosity (swell and change conformation)
What are the common uses of polymers in drug formulation?
- Excipients in tabletting (PVP/PEG)
- Tablet-coating
- Controlled release of drugs
- Excipients for semi-solid preparations
- Adhesive polymers for skin delivery
Give out examples of pharmacological polymers (7) and state each of their functions.
- Carboxypolymethylene (carbomer, carbopol): binding agent, emulsifying agent, emulsion stabilising agent, modified release agent, suspending agent
- Cellulose derivatives:
- Methylcellulose: coating agent, emulsifying agent, modified release agent, suspending agent, tablet binder, disintegrant, thickeners
- HPMC: capsule shell material, coating agent, dispersant, emulsifying agent, film forming agent, solubilising agent
- Natural gums: gum arabic (as adhesive and emulsifier), gum tragacanth (as thickener, emulsifier, suspending agent)
- Polyvinylpirrolidone (PVP): suspending agent
- Polyethylene glycol (PEG): viscosity agent, suspending agent, suppository base
Give out examples of water insoluble polymers and their general functions. What are the considerations of polymers while choosing them?
- Water insoluble polymers (ex. HDPE, polypropylene): used to make tubes, membranes, containers, caps
- Considerations of polymers
- Crystallinity may affect resistance to diffusion of small molecules
- Permeability to drugs (porous films) and gases (packaging)
- Affinity of molecules for adsorbing materials
- Ion exchange resins used to remove drugs
Describe the formation and properties of a gel. What is a xerogel? What are the types of gel?
- Formed by aggregating colloidal solid particles -> rigid structure of interlace network
- Small percentage of dispersed phase (<5% w/v)
- Xerogel: liquid removed from the gel -> framework
- Lyophobic gel: may be flocculated (regarded as continuous floccule)
- Lyophilic gel: type I gels (chemical: irreversible 3D networks crosslinked by chemical bonds) vs type II gels (physical: held by weak intermolecular bonds, heat reversible)
Explain the function and properties of surfactants.
- Reduce surface tension by moving to interphase (l/s or v/s or l/v)
- Facilitate emulsion formation/dispersion, improve wetting/used in drug delivery systems
- Amphipathic: have hydrophobic and hydrophilic regions
Explain the four types of surfactants and give out examples for each of them. Explain how micelles forming from surfactants could stabilise a drug formulation.
- Anionic surfactants: detergents, soaps, dispersants, wetting agents, antimicrobials (ex. SDS/SLS)
- Non-ionic surfactants: low toxicity (ex. Tween 20/80, polysorbates 20/80)
- Cationic surfactants: bactericides (ex. CTAB, cetrimide)
- Zwitterionic surfactants (ex. drugs such as betaines, phospholipids, Empigen BB)
- Micelles formation: when above critical micelle concentration (cmc) as no further reduction of surface tension can be achieved -> form (inverted) micelles -> used in liquid formulation to stabilise formulation/solubilise drugs
