Define suspension
Dispersion of finely divided solid particles in a liquid medium. The liquid medium may be aqueous or non-aqueous
Distinguish between suspension and emulsion
- Suspensions: solid particles in liquid medium
- Emulsions: 2 immiscible liquids stabilised by surfactants
The two broad categories of suspensions and their solid particle size?
- Coarse suspension: particle size >1 micron
2. Colloidal: particle size ≤ 1 micron
List some applications of suspensions as a pharmaceutical preparation
- PO
- Administer insoluble drugs in liquid form
- Mask distasteful drugs
- Effective in administering insoluble compounds for absorptive or antacid properties to treat gastric disorders - Injection: depot therapy (particle sdissolve slowly)
- External uses such as topical applications
List the ideal/desirable properties of suspensions
- Chemically stable
- Low sedimentation rate of particles
- Particles readily re-dispersed upon gentle shaking of container
- Constant particle size throughout storage
- Readily poured from container
- For injection: flow readily through syringe needle
- External use: spread easily, but not too mobile so that it will not run off surfaces when applied
What are the factors affecting the rate of sedimentation (Hint: Stoke’s Law)
Using Stoke’s law, velocity of the fall/rise of particle is:
- Proportional to: radius of particles and difference in densities between the particle and the dispersion medium
- Inversely proportional to the viscosity of the dispersion medium
What are floccules?
Solid particles in a suspension stick together
Distinguish between flocculated suspension and deflocculated suspension in terms of:
- Nature of dispersed phase
- Sedimentation rate
- Nature of final sediment
- nature of supernatant liquid
- Rheological property of concentrated suspension
Flocculated VS deflocculated suspension:
- Aggregates VS individual particles
- Rapid VS Slow
- Porous sediment on prolonged standing with relatively large volume and easy to re-disperse VS compact sediment, small volume and difficult to re-disperse
- Clear VS Cloudy
- Plastic flow with thixotropy VS dilatant flow
Name the two main components required in the formulation of a suspension, and list some other additives that could be added to the preparation
Main components:
- Dispersed phase, liquid vehicle
Other additives:
- Wetting agent, flocculating agent, thickening agent, pH buffer, preservative, colorant, flavour and fragrance
The dispersed phase of a suspension is also known as
Suspensoid
What are the two types of insoluble solid particles in the dispersed phase of a suspension, and what are their properties?
- Lyophilic solids:
- No need wetting agent to disperse in liquid vehicle
- May increase viscosity of suspension - Lyophobic solids:
- Require wetting agent for dispersion in liquid vehicle
What is the function of a wetting agent, and how does it carry out its function?
Function: Make solid particles more penetrable by dispersion medium
Modes of action:
1. Reduce solid-liquid interfacial tension
2. Imparts hydrophilicity to particle surface
which aids water in displacing the air pockets surrounding the crevices of drug particles
Wetting agents are usually pre-mixed with solid particles in preparation of suspensions.
What are some categories of wetting agents and some examples for each of the categories?
- Surfactants: HLB 7-9
- E.g. Spans, used at concentration below CMC - Hydrophilic polymers
- E.g. acacia, tragacanth, xanthan gum, povidone - Polyhydric alcohols
- E.g. glycerin, PEG, propylene glycol
List the three flocculating agents
- Electrolytes
- Surface active agents
- Hydrophilic polymers
In terms of zeta potential and other forces of attraction, explain microscopically what happens to solid particles in a suspension, if it was initially deflocculated
- Initially, zeta potential that causes interparticulate repulsion is more than the van der waals attractive forces, hence particles are repelled from each other and are deflocculated
- When low concentration of electrolytes are added, zeta potential is reduced below critical value, such that attractive VDW forces > repulsion by zeta potential, hence causing aggregation of particles and flocculation
- When high concentration of electrolytes are added, the polarity of zeta potential is reversed, causing a magnitude of interparticulate repulsion > VDW attractive forces, forming deflocculated suspension
What does Schulze-Hardy rule state about the relationship between effectiveness of electrolytes in aggregating particles and its valency?
Effectiveness of electrolyte in aggregating particles increases with valence of the ions (E.g. +2 ions are 10 times more effective than +1 ions)
Hence monovalent ions are sufficient to induce flocculation of weakly charged particles
What are the two types of surface active agents used as flocculating agents in a suspension?
- Ionic agents (which behaves like electrolytes)
2. Non-ionic agents
How does non-ionic surface active agents act as a flocculating agent?
- Used at a concentration above CMC
- Micelles formed and adsorbed at the surface of particles where they serve as bridge between particles, hence causing flocculation by bridging mechanism
How do hydrophilic polymers function as a flocculating agent?
Bridging mechanism
Explain microscopically what happens to the solid particles in a suspension as hydrophilic polymers are added
- At low conc. (<0.05%), hydrophilic polymers adsorbed at the surface of particles, serving as bridges between particles hence causing flocculation
- At higher concentration (0.05 - 0.1%), the polymers forms a protective coat around each drug particle, separating them from one another. This is known as protective colloid effect
- At even higher concentrations (>0.1%), polymers increases the viscosity of the medium by forming a network in the liquid medium of the suspension, improving stability but reducing flowability of the suspension (viscosity-enhancing effect)
What is the purpose of thickening agent in suspensions?
Assist the suspension of solid particles in the suspension
Which variable in the Stokes’ law is modified when a thickening agent is added into a suspension?
Viscosity of the medium
What are the two techniques employed in preparing a suspension?
- Dispersion technique
2. Precipitation technique
Why are colloid mills not very appropriate in the large-scale manufacture of suspensions?
Impart high shear, which can cause the size of the drug particle to be modified hence affecting the drug’s release profile
