Colloids

Question 1

Are colloids considered homogenous mixtures?

Answer 1

No, they are a type of heterogenous mixture (non-uniform composition)

Question 2

What is the difference between a colloid and suspension?

Answer 2

Colloid: Particles are medium and dispersed but do not settle

Suspension: Particle;ex are large, therefore they settle out

Question 3

What is a dispersed system?

Answer 3

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

Question 4

Are colloids dispersed systems?

Answer 4

Yes, because they contain undissolved or immiscible drug distributed throughout the vehicle

Question 5

Under dispersed systems, there are many different sub categories (colloids, gels, suspensions). What is the most important physiochemical difference between the different forms?

Answer 5

Size of the dispersed particles

Question 6

What are some general characteristics of colloids?

Answer 6

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)

Question 7

What are some unique properties of colloid delivery systems?

Answer 7

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

Question 8

Are all colloid particles spherical?

Answer 8

No, they have more than one shape

Ex. Globules, rods, flakes, threads or branched structures

Shape and size define flow, sedimentation and osmotic pressure

Question 9

What are the advantages of colloids?

Answer 9

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

Question 10

What are the three types of colloids?

Answer 10

Lyophillic (Hydrophillic) colloids

Lyophobic (Hydrophic) colloids

Association (amphiphillic) colloids

Question 11

What are micelles? (there will be a question on this concept review slide 17)

Answer 11

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.

Question 12

What is the difference between lyophillic or lyophobic colloids?

Answer 12

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)

Question 13

What is the Tyndall effect? (review picture on slide 19)

Answer 13

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

Question 14

Describe lyophillic/hydrophillic colloids in detail

Answer 14

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)

Question 15

Describe lyophobic colloids in detail

Answer 15

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

Question 16

What are sol—>gel transitions ?

Answer 16

It is the conversion of liquid state to gel state due to change in temperature or agitation

Question 17

What are some components of an inorganic colloid?

Answer 17

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)

Question 18

What are some components of an organic colloids?

Answer 18

They contain polymer macromolecules that dissolve in water (single phase system)

Ex. Clindoxyl gel

Question 19

What is the defining quality of a hydrogel solvent?

Answer 19

Dispersible in water

Ex. Milk of magnesia

Question 20

What are some qualities of an organogel?

Answer 20

They are not dispersible in water

Ex. Petrolatum, cocoa butter, carbowaxes, PEG ointments)

Question 21

What is the difference between a jelly and a xerogel?

Answer 21

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)

Question 22

What are differences between colloids and suspensions?

Answer 22

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

Question 23

What are gelling agents?

Answer 23

They are pharmaceutical excipients used to form gels via high degree of cross-linking and entanglement

Gelling agents increase medium viscosity

Question 24

What is the concentration of gelling agents in the usual gel?

Answer 24

Between 0.5-5%, and can be up to 10%

Higher the gelling agent, the more stiff the gel

Question 25

What are some natural polymers?

Answer 25

Acacia and tragacanth

Question 26

What are some examples of semi-synthetic polymers?

Answer 26

Cellulose derivatives like methylcellulose

Question 27

What are some examples of synthetic polymers?

Answer 27

Carbomers and polaxamers

Question 28

What are some qualities with alginic acid as a gelling agent?

Answer 28

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)

Question 29

What are some qualities of tragacanth as a gelling agent?

Answer 29

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

Question 30

What are some qualities of methylcellulose as a gelling agent?

Answer 30

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

Question 31

What are some qualities of hydroxypropylmethyl cellulose (HPMC) as a gelling agent?

Answer 31

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

Question 32

What are some qualities of Carbomers as gelling agents?

Answer 32

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

Question 33

What are some qualities associated with poloxamers as gelling agents?

Answer 33

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)

Question 34

What is PLO gel?

Answer 34

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

Question 35

Are organogels like PLO clear?

Answer 35

No, they are usually off white

Hydrogels are more clear

Question 36

What are some qualities patients prefer in gels?

Answer 36

Patients prefer clear, water-washable, and non-greasy gels

This is not always possible, so some gels are turbid

Question 37

What can cause clumping in gels?

Answer 37

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

Question 38

How can clumping be reduced in gels?

Answer 38

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

Question 39

What are some compounding considerations?

Answer 39

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

Question 40

When should the gel be added to a formulation before or after the active drug?

Answer 40

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

Question 41

What is Brownian motion?

Answer 41

The zig-zag movement of colloidal particles continuously and randomly

Brownian movement was more rapid for smaller particles, but it decreased with increased viscosity

Question 42

How can particles in a liquid medium become charged?

Answer 42

Selective adsorption of a particular ionic species

Ionization of groups on the particle surface

Adsorption of ionic surfactant molecules to the particle

Question 43

What is the significance of charged particles in a colloid?

Answer 43

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

Question 44

What are the two charged planes next to a charged particle?

Answer 44

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

Question 45

What is the DLVO theory of particle stability?

Answer 45

It estimates the stability of hydrophobic sold

Total potential energy = van der waals attraction + electrostatic repulsion

Question 46

What happens at the primary minimum in terms of attractive force felt by two particles?

Answer 46

This is where two particles are aggregated together. This is the lowest energy state (preferred state)

Question 47

What happens at the primary maximum in terms of attractive forces felt by two particles?

Answer 47

Repulsion is greater than attraction. The particles at this distance are going to repel each other (ideal state of dispersion)

Question 48

What happens at the secondary minimum in terms of attractive force felt by two particles?

Answer 48

At this distance, the charges become very small. This allows for easy dispersion

Question 49

Attractive forces predominate at both primary and secondary minimums, what is the difference?

Answer 49

At secondary minimum (reversible loose aggregation/flocculated particle, shaking can overcome aggregation, preferred for a suspension)

Question 50

Do flocculated particles settle out of the medium?

Answer 50

No, deflocculated (tightly aggregated) particles will cake when left to stand

Question 51

What is the difference between colloidally and pharmaceuticals stable?

Answer 51

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

Question 52

Can settled deflocculated particles be easily redispersed via shaking?

Answer 52

No, they are tightly packed and form a cake. There is no water between the particles to help shake up the particles

Question 53

What are protective colloids?

Answer 53

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)

Question 54

Does decreasing viscosity help improve stability?

Answer 54

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)