Colloids Flashcards
Are colloids considered homogenous mixtures?
No, they are a type of heterogenous mixture (non-uniform composition)
What is the difference between a colloid and suspension?
Colloid: Particles are medium and dispersed but do not settle
Suspension: Particle;ex are large, therefore they settle out
What is a dispersed system?
A disperse system may be defined as a system in which one substance (the disperse phase) is distributed as particles throughout another phase (dispersion medium)
Dispersion phase and medium could be solid, liquid, or gas
Are colloids dispersed systems?
Yes, because they contain undissolved or immiscible drug distributed throughout the vehicle
Under dispersed systems, there are many different sub categories (colloids, gels, suspensions). What is the most important physiochemical difference between the different forms?
Size of the dispersed particles
What are some general characteristics of colloids?
Particle size 1-500nm (too small to see)
Excellent candidate for novel nano-drug delivery systems
Large surface area (improved absorption, efficacy, and delivery into the tissues)
What are some unique properties of colloid delivery systems?
Cellular uptake of nano particles is different from micro/macro particles
In drugs that have a hard time penetrating into tissues, they may be formulated into nano particles. Nanoparticles have better absorption, efficacy, and tissue penetration
Colloids can also protect the drug from metabolic processes
Are all colloid particles spherical?
No, they have more than one shape
Ex. Globules, rods, flakes, threads or branched structures
Shape and size define flow, sedimentation and osmotic pressure
What are the advantages of colloids?
Increased surface area of absorption
Reduce side effects of the drug die to low retention time and exposure to mucosal membrane
Stability and solubility enhancement
What are the three types of colloids?
Lyophillic (Hydrophillic) colloids
Lyophobic (Hydrophic) colloids
Association (amphiphillic) colloids
What are micelles? (there will be a question on this concept review slide 17)
Surfactants when added to a solvent like water will arrange their hydrophilic ends towards the water while pushing their hydrophobic ends together. This effectively shields the hydrophobic regions from water.
This only occurs after a certain concentration (critical micelle concentration) of surfactant is achieved. Below this concentration, the surfactants remain on the surface of the solvent. The hydrophillic ends point down, while hydrophobic ends point into the sky.
What is the difference between lyophillic or lyophobic colloids?
Lyophillic colloids are solvent loving
Ex. True solutions, gels, particulate dispersion
Lyophobic colloids are solvent hating (little or no attraction between the particle and vehicle)
What is the Tyndall effect? (review picture on slide 19)
In colloids, the light is reflected through the entire mixture due to the particles distributed in the medium
In solutions, the light will not illuminate the mixture bc small particle size
Describe lyophillic/hydrophillic colloids in detail
Affinity to dispersion medium (solvent loving/solvation)
Hydrate when dispersed in water. Hydration causes the colloids to swell and increase system viscosity
Thermodynamically stable (spontaneously disperse)
Describe lyophobic colloids in detail
Most common form of colloidal dosage form
semi-solid or semi-rigid
Particles form an intercalating structure that increases viscosity
Thermodynamically unstable (changes in the environment can cause aggregation and precipitation)
Can perform sol—>gel or gel—>sol transitions
What are sol—>gel transitions ?
It is the conversion of liquid state to gel state due to change in temperature or agitation
What are some components of an inorganic colloid?
Also known as particulate collloids, magmas, or milk.
Thy contain small discrete particles (two phase system)
Ex. Milk of magnesia (thixotropic = opposite of non-Newtonian fluid)
What are some components of an organic colloids?
They contain polymer macromolecules that dissolve in water (single phase system)
Ex. Clindoxyl gel
What is the defining quality of a hydrogel solvent?
Dispersible in water
Ex. Milk of magnesia
What are some qualities of an organogel?
They are not dispersible in water
Ex. Petrolatum, cocoa butter, carbowaxes, PEG ointments)
What is the difference between a jelly and a xerogel?
Jelly (a gel that is rich in liquid):
Formed by addition of thickening agents and are subject to microbial contamination
Xerogel (a gel that has water removed from it)
What are differences between colloids and suspensions?
Colloids:
Small particle size (invisible)
Particles do not settle out, but lyophobic colloids show visible sedimentation due to aggregation
Suspension:
Large particle size (visible)
Always settle at bottom when left to stand
What are gelling agents?
They are pharmaceutical excipients used to form gels via high degree of cross-linking and entanglement
Gelling agents increase medium viscosity
What is the concentration of gelling agents in the usual gel?
Between 0.5-5%, and can be up to 10%
Higher the gelling agent, the more stiff the gel
What are some natural polymers?
Acacia and tragacanth
What are some examples of semi-synthetic polymers?
Cellulose derivatives like methylcellulose
What are some examples of synthetic polymers?
Carbomers and polaxamers
What are some qualities with alginic acid as a gelling agent?
Obtained from seaweed
Concentration ranges from 1-5% and can take about 30 min to get dispersed in water
Prone to microbial growth (must have preservatives like parabens)
What are some qualities of tragacanth as a gelling agent?
It is usually used as a gelling agent in formulations with a pH within (4 - 8)
Requires addition of preservatives
Powdered tragacanth tends to form lumps in water, so wetting agents like glycerin are often added
What are some qualities of methylcellulose as a gelling agent?
Has a relatively wide pH range from (3-11)
It makes thinner gels and will hydrate in hot water rather than cold water, unlike other gelling agents
High tolerance for added drugs and salts
Good solvent compatibility with water, alcohol, and propylene glycol
Cooling for an hour improves clarity and viscosity. Clear gels can help determine if a microrganism is proliferating or not
What are some qualities of hydroxypropylmethyl cellulose (HPMC) as a gelling agent?
Makes thicker gels compared to other gelling agents
It is compatible with both water and alcohol-based formulations
Good gelling agent for time release preparations
Disperses well in cool water, similar to other gelling agents
What are some qualities of Carbomers as gelling agents?
High bulk density and create acidic aqueous solutions (pH 3)
Due to the low pH that results from adding Carbomers, a neutralizer is added (only in Carbomers)
Thickens at pH 5-6, expanding to 1000 times original volume
Sprinkled in medium with rapid stirring to avoid clumping
What are some qualities associated with poloxamers as gelling agents?
Copolymers of polyethylene and polyoxypropylene
Poloxamer gel is used widely in extemporaneous compounding
They are also absorption enhancing topical vehicles
Form reverse thermal gels (dissolve in cold water rather than hot water)
What is PLO gel?
PLO is an acronym for Pluronic(Poloxamer) Lecithin Organogel. It’s It is a mixture of a poloxamer, lecithin, isopropyl palmitate —> PLO gel
This gel is often used when making high strength diclofenac
Are organogels like PLO clear?
No, they are usually off white
Hydrogels are more clear
What are some qualities patients prefer in gels?
Patients prefer clear, water-washable, and non-greasy gels
This is not always possible, so some gels are turbid
What can cause clumping in gels?
This can occur when the gelling agent is added to rapidly.
The powder that hits the medium first will hydrate, but prevent the rest of the gelling agent to get hydrated
How can clumping be reduced in gels?
Sift the powder into teh vortex of stirring medium
Levitate the powder with water miscible non-solvent like alcohol, glycerin, or propylene glycol
Use a blender to homogeneously mix the powder
What are some compounding considerations?
Pre-adjust the temperature of water based on the solubility profile of the polymer (some dissolve in hot water, while other dissolve better in cold water)
Carbomers require pH adjustment
Most gelling agents need 1-2 days to completely hydrate an reach maximum viscosity and clarity
Excessive mixing can introduce air bubbles. In more viscous colloids, the bubbles will remain
When should the gel be added to a formulation before or after the active drug?
It really depends on the properties of each drug
Does the drug interfere with the gelling process?
Is drug stable at conditions of temperature and pH experienced when adding a gelling agents
The preference is towards adding the drug prior to making the gel, it is simply easier and results in a more uniform dispersion
What is Brownian motion?
The zig-zag movement of colloidal particles continuously and randomly
Brownian movement was more rapid for smaller particles, but it decreased with increased viscosity
How can particles in a liquid medium become charged?
Selective adsorption of a particular ionic species
Ionization of groups on the particle surface
Adsorption of ionic surfactant molecules to the particle
What is the significance of charged particles in a colloid?
The electrical double layer determines the distance between adjacent particles in the dispersion. The measure of theses charges within a dispersion is called a zeta potential
Directly affects the stability of the system
What are the two charged planes next to a charged particle?
The stern plane includes tightly bound positive charges
The slipping plane is a less tightly bond collection of charges that are attracted to the original charged particle
What is the DLVO theory of particle stability?
It estimates the stability of hydrophobic sold
Total potential energy = van der waals attraction + electrostatic repulsion
What happens at the primary minimum in terms of attractive force felt by two particles?
This is where two particles are aggregated together. This is the lowest energy state (preferred state)
What happens at the primary maximum in terms of attractive forces felt by two particles?
Repulsion is greater than attraction. The particles at this distance are going to repel each other (ideal state of dispersion)
What happens at the secondary minimum in terms of attractive force felt by two particles?
At this distance, the charges become very small. This allows for easy dispersion
Attractive forces predominate at both primary and secondary minimums, what is the difference?
At secondary minimum (reversible loose aggregation/flocculated particle, shaking can overcome aggregation, preferred for a suspension)
Do flocculated particles settle out of the medium?
No, deflocculated (tightly aggregated) particles will cake when left to stand
What is the difference between colloidally and pharmaceuticals stable?
Deflocculated particles are textbook definitions of a stable colloid. They are not stuck to each other and are independent particles, but they will settle out and form cake
Flocculated particles on the other hand have great stability, but their loose aggregation does not agree with colloid properties
Can settled deflocculated particles be easily redispersed via shaking?
No, they are tightly packed and form a cake. There is no water between the particles to help shake up the particles
What are protective colloids?
A combination of a lyophillic (medium loving) and lyophobic (medium hating) can reduce the destabilizing effects of the electrolytes in the medium (effectively reduce settling)
Does decreasing viscosity help improve stability?
Yes, increasing viscosity of the system improves stability (less settling out)
Viscous medium restricts particle movement, slow settling of particles = water can get trapped between settled particles (allows for ease of redispersion)
