Topic 14 - Suspensions

Question 1

What is the offset when it comes to using suspensions as a dosage form?

Answer 1

Liquid dosage form containing sufficient drug in a reasonable small volume, but the drug is in an unstable from in the solution.

Question 2

T/F: Oral suspensions are best for the elderly and children

Answer 2

T

Question 3

Examples of oral suspensions

Answer 3

Antacids (heat burn/reflux), Tetracycline (HCl), indomethacin (INSAID)

Question 4

What is the risk associated with shaking a topical suspension?

Answer 4

Risk it might settle to the bottom, so it needs to be redistributed

Question 5

Examples of topical suspensions

Answer 5

Calamine lotion (anti-itching), hydrocortisone (mild topical corticosteroid), betamethasone (corticosteroid)

Question 6

Lacrimal gland function

Answer 6

• Releases fluid with nutrients, enzymes, etc. 70% replenishes with every blink
• Regulates pH

Question 7

What is the biggest challenge with ophthalmics?

Answer 7

Every time there’s a blink, there’s fluid turnover. The fluid drains, and the gland replaces the eye fluid

Question 8

Examples of intramuscular suspensions

Answer 8

Procaine penicillin G, insulin Zinc, extended insulin zinc, contraceptive steroids

Question 9

Disadvantages of suspensions (5)

Answer 9

• Uniformity and accuracy of dose not as good as tablet/capsule
• Sedimentation, cake formation
• Product is liquid and bulky
• Formulation of effective suspension is more difficult than for tab/cap
• Heating and cooling cycles will affect size distribution of particles

Question 10

How do heating and cooling cycles affect size distribution of the particles?

Answer 10

Saturation concentrations decrease at colder temperatures and increase at warmer temperatures. Particles get smaller, so more is dissolved at high temps.

Question 11

Overall suspension formulation criteria (3)

Answer 11

1. Slow settling and readily dispersed when shaken
2. Constant particle size throughout long periods of standing
3. Pours readily and easily, or flows easily through needle

Question 12

Lotion-specific formulation criteria

Answer 12

1. Spreads over surface but does not run off
2. Dry quickly, remain on skin, provide an elastic protective film containing the drug
3. Acceptable odor and colour

Question 13

Settling

Answer 13

When the force of friction against a fluid balances with the force of fluid keeping the object buoyant

Question 14

What can be done to reduce settling?

Answer 14

• Decrease diameter (commonly)
• Reduce density
• Viscosity of continuity phase increase (common)

Question 15

What results in high surface free energy?

Answer 15

Large surface area of dispersed particles

Question 16

How else can we reduce surface free energy?

Answer 16

Reducing interfacial tension (using surfactants)

Question 17

How is flocculation determined?

Answer 17

Using forces of attraction (van der Waals) vs. forces of repulsion (electrostatic)

Question 18

Deflocculated vs. flocculated

Answer 18

D: repulsion > attraction, affected by [electrolytes]

F: Attraction > repulsion

Question 19

What is caking?

Answer 19

High forces of attraction between particles in suspension cause cake to form, which can never come apart

Question 20

Particles may become charged by… (2)

Answer 20

• Adsorption of ionic species pres in sol’n or preferential adsorption of OH-
• Ionization of -COOH or -NH2 group

Question 21

What two factors influence distribution of ions in the medium?

Answer 21

• Thickness of layers
• Sat concentration

Question 22

Nernst potential

Answer 22

Potential difference from the surface of the charged solid to the electroneutral bulk

Question 23

Zeta potential

Answer 23

Potential difference between surface of tightly bound charged layer (on top of charged surface) and electroneutral bulk. Governs electrostatic force of repulsion between solid particles

Question 24

Debye length

Answer 24

When electrical potential energy approaches zero

Question 25

Describe the DVLO graph

Answer 25

- Total potential energy of interaction vs. Distance between particles (H) - At H = 0, tpei < 0 (caking) - H eventually reaches a peak when tpei > 0 - As H continues, it reaches an attractive > repulsive dip (reversible)

Question 26

DVLO theory

Answer 26

Adding electrolytes to sol'n changes interactions. Overall, the highest peak is reduced but the second well is decreased as well.

Question 27

What is the main advantage to deflocculation?

Answer 27

Particles settle slowly and this looks aesthetically pleasing

Question 28

What allows flocculated suspensions to have relatively good shelf lives?

Answer 28

Easily re-suspended

Question 29

2 types of flow exhibited by flocculated particles in suspension

Answer 29

Pseudoplastic or plastic flow

Question 30

T/F: Deflocculated systems exhibit Bingham plastic behaviour

Answer 30

F: Newtonian

Question 31

Why does bentonite make a good 2-phase gel?

Answer 31

Gels keep particles separated. There are diff charges between the face of the gel and the edge of the gel, which means particles never come tohether. Bentonite is a natural clay which never dissolves, and suspends upon shaking. It's also edible!

Question 32

Characteristics of single phase gels (3)

Answer 32

- entangled polymer chains in solution - if increase concentration or decrease hydration of polymer chain, then form a gel - Temp, concentration, mol wt. influence gel formation

Question 33

Thixotropy

Answer 33

Slow recovery of viscosity lost through shearing

Question 34

Hysteresis

Answer 34

Gel-solid-gel transformation

Question 35

Why is thixotropy desirable?

Answer 35

- Gel state resists particle settling - Becomes a fluid on shaking and readily dispensed

Question 36

T/F: Increasing viscosity increases the rate of drug formation

Answer 36

F: Decreases the rate of drug absorption due to a decrease in the dissolution rate

Question 37

When increasing the viscosity of a drug, what happens to the effectiveness of the drug?

Answer 37

Extent of absorption doesn't usually change, but it may reduce the effectiveness of drugs with a low therapeutic window

Question 38

2 common approaches to formulation of suspension

Answer 38

1. Use structured vehicle (gel) issue: caking 2. Flocculation (change size, salt content, etc)

Question 39

What can we use to control flocculation? (3)

Answer 39

- Electrolytes - Polymers - Alcohol

Question 40

Adding electrolytes may change ____, which may in affect ____ potential in turn.

Answer 40

pH, zeta

Question 41

Examples of polymers added to suspensions

Answer 41

Sodium alginate, sodium starch

Question 42

How do polymers increase the viscosity of suspensions?

Answer 42

Polymer interacting with two particles at the same time, so they're more likely to interact in a controlled manner

Question 43

Examples of structured vehicles for deflocculated suspensions

Answer 43

Methylcellulose, bentonite

Question 44

Steps to prepare suspension

Answer 44

1. Reduce drug powder to desired size 2. Add drug and wetting agent to solution 3. Prepare solution of suspending agent 4. Add other ingredients (electrolytes, colour, flavour) 5. Homogenize medium 6. Package