Topic 14 - Suspensions Flashcards
What is the offset when it comes to using suspensions as a dosage form?
Liquid dosage form containing sufficient drug in a reasonable small volume, but the drug is in an unstable from in the solution.
T/F: Oral suspensions are best for the elderly and children
T
Examples of oral suspensions
Antacids (heat burn/reflux), Tetracycline (HCl), indomethacin (INSAID)
What is the risk associated with shaking a topical suspension?
Risk it might settle to the bottom, so it needs to be redistributed
Examples of topical suspensions
Calamine lotion (anti-itching), hydrocortisone (mild topical corticosteroid), betamethasone (corticosteroid)
Lacrimal gland function
- Releases fluid with nutrients, enzymes, etc. 70% replenishes with every blink
- Regulates pH
What is the biggest challenge with ophthalmics?
Every time there’s a blink, there’s fluid turnover. The fluid drains, and the gland replaces the eye fluid
Examples of intramuscular suspensions
Procaine penicillin G, insulin Zinc, extended insulin zinc, contraceptive steroids
Disadvantages of suspensions (5)
- 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
How do heating and cooling cycles affect size distribution of the particles?
Saturation concentrations decrease at colder temperatures and increase at warmer temperatures. Particles get smaller, so more is dissolved at high temps.
Overall suspension formulation criteria (3)
- Slow settling and readily dispersed when shaken
- Constant particle size throughout long periods of standing
- Pours readily and easily, or flows easily through needle
Lotion-specific formulation criteria
- Spreads over surface but does not run off
- Dry quickly, remain on skin, provide an elastic protective film containing the drug
- Acceptable odor and colour
Settling
When the force of friction against a fluid balances with the force of fluid keeping the object buoyant
What can be done to reduce settling?
- Decrease diameter (commonly)
- Reduce density
- Viscosity of continuity phase increase (common)
What results in high surface free energy?
Large surface area of dispersed particles
How else can we reduce surface free energy?
Reducing interfacial tension (using surfactants)
How is flocculation determined?
Using forces of attraction (van der Waals) vs. forces of repulsion (electrostatic)
Deflocculated vs. flocculated
D: repulsion > attraction, affected by [electrolytes]
F: Attraction > repulsion
What is caking?
High forces of attraction between particles in suspension cause cake to form, which can never come apart
Particles may become charged by… (2)
- Adsorption of ionic species pres in sol’n or preferential adsorption of OH-
- Ionization of -COOH or -NH2 group
What two factors influence distribution of ions in the medium?
- Thickness of layers
- Sat concentration
Nernst potential
Potential difference from the surface of the charged solid to the electroneutral bulk
Zeta potential
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
Debye length
When electrical potential energy approaches zero
Describe the DVLO graph
- 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)
DVLO theory
Adding electrolytes to sol’n changes interactions. Overall, the highest peak is reduced but the second well is decreased as well.
What is the main advantage to deflocculation?
Particles settle slowly and this looks aesthetically pleasing
What allows flocculated suspensions to have relatively good shelf lives?
Easily re-suspended
2 types of flow exhibited by flocculated particles in suspension
Pseudoplastic or plastic flow
T/F: Deflocculated systems exhibit Bingham plastic behaviour
F: Newtonian
Why does bentonite make a good 2-phase gel?
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!
Characteristics of single phase gels (3)
- 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
Thixotropy
Slow recovery of viscosity lost through shearing
Hysteresis
Gel-solid-gel transformation
Why is thixotropy desirable?
- Gel state resists particle settling
- Becomes a fluid on shaking and readily dispensed
T/F: Increasing viscosity increases the rate of drug formation
F: Decreases the rate of drug absorption due to a decrease in the dissolution rate
When increasing the viscosity of a drug, what happens to the effectiveness of the drug?
Extent of absorption doesn’t usually change, but it may reduce the effectiveness of drugs with a low therapeutic window
2 common approaches to formulation of suspension
- Use structured vehicle (gel) issue: caking
- Flocculation (change size, salt content, etc)
What can we use to control flocculation? (3)
- Electrolytes
- Polymers
- Alcohol
Adding electrolytes may change ____, which may in affect ____ potential in turn.
pH, zeta
Examples of polymers added to suspensions
Sodium alginate, sodium starch
How do polymers increase the viscosity of suspensions?
Polymer interacting with two particles at the same time, so they’re more likely to interact in a controlled manner
Examples of structured vehicles for deflocculated suspensions
Methylcellulose, bentonite
Steps to prepare suspension
- Reduce drug powder to desired size
- Add drug and wetting agent to solution
- Prepare solution of suspending agent
- Add other ingredients (electrolytes, colour, flavour)
- Homogenize medium
- Package
