Suspensions

Question 1

What is a pharmaceutical suspension?

Answer 1

a coarse dispersion containing:
-finely divided particulate material suspended in a liquid or
semisolid medium (continuous phase or vehicle)

Question 2

What is the criteria for a suspension?

Answer 2

particles are uniformly distributed
particles have minimal solubility in the continuous phase
the size distribution of the particles ranges from 1-100um
- 1-50um: fine dispersion
- 50-100um: coarse dispersion

Question 3

What are the advantages of suspensions?

Answer 3

deliver poor water-soluble drugs
suitable for patients with difficulty in swallowing a tablet or capsule
palatability (masking taste)
chemical stability
sustained release
can be given for both systemic (antibiotics) and local therapeutic effects (activated charcoal to adsorb excess Gi fluids)

Question 4

What are the disadvantages of suspensions?

Answer 4

physical instability, settling over time results in lack of uniformity of the dose
manufacturing difficulties

Question 5

Describe the preparation of acceptable suspensions.

Answer 5

should not precipitate rapidly
redispersed quickly by shaking
correct viscosity to pour from the bottle/flow through an administration needle
for topical formulations sufficiently fluid to spread over the skin

Question 6

What are the two phases of a suspension?

Answer 6

internal phase (drug, active, or dispersed phase)
external phase (dispersion medium, vehicle)

Question 7

What are the solids that can be used in the internal phase of a suspension?

Answer 7

hydrophilic solids: readily wetted by water
-clays (kaolin, talc, magnesium aluminum silicate)
-hydroxides and oxides of calcium, magnesium, zinc,
aluminum & titanium
hydrophobic solids: not wetted by water, but “wetted” by oils
-most pharmaceutical substances: charcoal, sulfur, aspirin,
phenobarbital

Question 8

What is the selection of the external phase based on?

Answer 8

safety
density
viscosity (important in stability)
taste stability

Question 9

What are some liquids that can be used in the internal phase of suspensions?

Answer 9

polar liquids:
-water: up to 100%
-simple syrup (sucrose): 50-100%
-cherry syrup: 50-100%
non-polar liquids:
-oils: up to 100%
-fatty esters: up to 100%
-hydrocarbons: up to 100%
structured vehicles:
-acacia: 0.5-2%
-tragacanth: 0.5-5%
-carbopol: 0.5-5%
-methyl cellulose derivatives: 0.5-5%
-colloidal silicon dioxide: 1.5-3.5%

Question 10

What are structural vehicles?

Answer 10

0.5-5% polymer in final composition
aqueous dispersions of polymeric materials

Question 11

What are the properties of structured vehicles?

Answer 11

protective colloids at low concentrations, while they function as viscosity-inducing agents at higher concentrations
-concentration varies based on viscosity requirement
some thixotropic behaviour may also be observed (by stirring or shaking)
-not used for parenteral administration

Question 12

What are the other ingredients used in suspensions?

Answer 12

buffers
colouring agents
flavours
sweetening agents
preservatives
suspending (flocculating) agents
viscosity modifiers

Question 13

What are examples of suspending (flocculating) agents?

Answer 13

electrolytes
ionic surfactants
polymeric flocculating agents

Question 14

Describe electrolytes as suspending agents.

Answer 14

capable of reducing zeta potential
ex: sodium chloride, calcium salts
concentration of electrolyte used: 0.01-1%

Question 15

Describe ionic surfactants as suspending agents.

Answer 15

capable of decreasing zeta potential

Question 16

Describe polymeric flocculating agents as suspending agents.

Answer 16

form a gel-like network to cross-link the suspended particles
also increase viscosity (i.e methylcellulose)

Question 17

What are examples of viscosity modifiers?

Answer 17

polysaccharides
water soluble cellulose derivatives
hydrated silicates
acrylic acid polymers
colloidal silicon dioxide

Question 18

Describe polysaccharides as viscosity modifiers.

Answer 18

used only for extemporaneous compounding because of their increased susceptibility to microbial growth
ex: acacia gum, tragacanth, alginates

Question 19

Describe water soluble cellulose derivates as viscosity modifiers.

Answer 19

semi-synthetic cellulose derivatives make greater viscosity ranges available by combining agents in specific proportions
ex: methylcellulose, MCC

Question 20

What is an examples of a hydrated silicate?

Answer 20

bentonite

Question 21

Describe acrylic acid polymers as viscosity modifiers.

Answer 21

high molecular weight cross-linked polymers of acrylic acid forms gels in neutralized aqueous dispersions
ex: Carbopol (carboxypolyethylene)

Question 22

Describe colloidal silicon dioxide as viscosity modifiers.

Answer 22

“fluffy” white powder used as either a suspending/thickening agent or a tablet/capsule diluent

Question 23

What are the properties of an ideal suspending agent/viscosity modifier?

Answer 23

readily dissolved/dispersed without special techniques
readily and uniformly incorporated into the formulation
ensures formulation of loosely packed system (flocculated)
no effect on the bioavailability of the drug
inert, no incompatibilities with other components
stability over wide pH range

Question 24

What are some examples of oral suspensions?

Answer 24

antibiotics
antacids
radiopaque suspensions

Question 25

What is an example of a topical suspension?

Answer 25

calamine lotion

Question 26

What are some examples of parenteral suspensions?

Answer 26

intramuscular
subcutaneous
intralesional
intraarticular

Question 27

Describe deflocculated suspensions.

Answer 27

dispersed particles are small, discrete units
the smaller the particle size, the slower the gravitational setting
because of slow settling no liquid becomes trapped between particles
sediment is compacted and very difficult to redisperse; small volume of sediment
the supernatant remains cloudy even after settling occurs

Question 28

What is a serious physical problem with deflocculated suspensions?

Answer 28

caking

Question 29

Which type of products should not be formulated as deflocculated suspensions?

Answer 29

products which must be stored for a long period of time

Question 30

Describe flocculated suspensions.

Answer 30

dispersed particles form loose aggregates (flocs)
particles settle as flocs
the rate of sedimentation is relatively rapid
the sediment contains trapped liquid between flocs making the volume of sediment large and “fluffy” (a hard cake doesnt form)
the loosely packed sediment is easily redispersed by moderate aggregation
the supernatant is relatively clear after settling occurs

Question 31

What are the properties of well formulated pharmaceutical suspensions?

Answer 31

must be easily resuspendable
after shaking the dispersed phase is suspended long enough to remove a dose
particles should be sufficiently small to appear smooth
has suitable viscosity

Question 32

What happens with high zeta potential?

Answer 32

repulsive forces>attractive forces
system will be dispersed or deflocculated
upon settling the suspension will cake–>difficult to resuspend

Question 33

What happens with low zeta potential?

Answer 33

attractive forces>repulsive forces
system will be flocculated (prevents caking)

Question 34

What are some compounding tips for suspensions?

Answer 34

dust masks should be worn when working with powders
aerosolizing powders make them easier to work with, by compacting them with a few drops of alcohol, water or mineral oil, as appropriate
magnesium stearate, <1% enhances flowability
sodium lauryl sulfate, <1% neutralizes static electricity