W11.2_Suspensions

Question 1

Contrast solutions and suspensions in terms of definition, appearance, particle sizes, and stability.

Answer 1

Definition
- Solution: homogenous mixture
- Suspension: heterogeneous mixture
Appearance
- Solution: clear and transparent
- Suspension: opaque or cloudy
Particle size
- Solution: dissolved, less than 1nm
- Suspension: larger particles, 0.5-100µm
Stability
- Solution: more stable, particles evenly distributed
- Suspension: may require shaking before use to redistribute the particles

Question 2

Define suspension. Explain its pharmacological use and desirable qualities.

Answer 2

• Definition: solid particles with low solubility dispersed in a phase (colloidal suspensions)
• High concentration of drugs (usually >2% w/v)
• Uses: hide unpleasant taste, lotions to deposit fine powder on skin, slow release formulation, for patients with difficulty swallowing, higher bioavailability
• Desirable qualities: particles should settle slowly, disperse easily on shaking, no caking or clumping, pourable from bottle/flow through a needle/spread easily on skin without running away, good electrical properties, easily made, no change in crystal size/form during storage, not support microbial growth, chemically stable, enough bioavailability

Question 3

Explain how caking could occur in suspensions.

Answer 3

• Gravity will influence behaviour (Stoke’s law + DLVO): particles will eventually sediment and settle at bottom of container (faster for large particles)
• Caking: particles at bottom compressed by weight above (sufficient energy to overcome primary maximum to form irreversible reaction at secondary minimum)

Question 4

Flocculation is really important in pharmaceutical suspensions. Define a floc. Describe the characteristics of flocculated and deflocculated suspensions and explain which one is the best.

Answer 4

• Floc/flocculate: cluster of particles held in loose open structure (vdW), spontaneously formed and broken down
• Flocculated suspension: moderately deep secondary minimum -> decrease in repulsion potential
• Characteristics: voids in sediment, high volume, rapidly obtained, easy to redisperse, no caking
• Deflocculated suspension: high potential of repulsion -> particles may overcome primary energy barrier and become irreversibly bound together (caking)
• Characteristics: no flocs initially, slow sediments independently for particles, closely packed with no voids, susceptible to caking
• ∴ Best suspension: partially flocculated (slow sedimentation and easy to disperse)

Question 5

Explain how flocculation is controlled via ions. Why are trivalent ions not used?

Answer 5

• Low electrolyte concentration: large primary maximum (deflocculated)
• High electrolyte concentration: no primary maximum (flocculated)
• Intermediate electrolyte concentration: small primary maximum with secondary minimum (best)
  Ions arranged in order to aggregate hydrophobic colloids
• Most common: sodium salts (monovalent)
• Trivalent ions: more efficient but toxic (excess positive charges would disrupt the stability of negatively charged membrane -> collapse)

Question 6

Explain how flocculation is controlled via polymers by giving some examples. What would happen when polymers are too concentrated?

Answer 6

• ex. Starch alginates, cellulose derivatives, tragacanth, carbomers, silicate
• Linear branched chains form gel-like network -> adsorbed on dispersed particles to become protective colloid
• Excessive blending/high concentration of polymers: inhibit crosslinking between adjacent particles -> deflocculated system

Question 7

Explain some of the other pharmaceutical considerations for suspensions (2).

Answer 7

• Wetting properties: insoluble agents have to be wetted by surfactants to reduce interfacial tension -> reduce risk of aggregation
• Particle size: must be controlled by controlled precipitation (chemical) or milling (physical)
• Smaller particles have higher dissolution rate but crystallisation may happen at surface of larger particles -> smaller particles would dissolve in solution and adsorb/crystallise on surface of of large particles -> crystal growth (Ostwald ripening) (can also be seen in w/o emulsions)