Medicinal Suspensions Notes

Learning Outcomes

• Definition of Pharmaceutical Suspension: A pharmaceutical suspension involves a dispersion of fine, insoluble solid particles (disperse phase) in a liquid (continuous phase or dispersion medium).

• Properties of a Well-Formulated Suspension:

  • Small, uniformly sized disperse phase particles that settle slowly.

  • Settled particles should not form hard, compact sediment that’s challenging to disperse.

  • Dosing consistency: Each dose should contain the same amount of suspended solid.

  • Acceptable sensory attributes: Odor, color, taste, and texture should be pleasant.

  • The continuous phase should prevent microbial growth during storage.

Oral Route: Suspensions

• Origin:

  • From Latin "oralis" - mouth; refers to drugs administered orally.

  • Examples include oral suspensions like paracetamol (e.g. Disprol™, Calpol™).

Types of Disperse Phases

• Solid Particles Size:

  • Coarse Suspensions: Particles greater than 1 mm.

  • Colloidal Dispersions: Particles less than 1 mm.

• Continuous Phase: Typically aqueous but can include organic or oil-based mediums.

  • Example: Magnesium hydroxide suspension, available as ‘Milk of Magnesia’ or ‘Magnesium Hydroxide Mixture BP’.

  • Example: Aqueous suspension containing magnesium hydroxide and liquid paraffin.

Advantages of Well-Formulated Suspensions

• They are beneficial for patients who struggle to swallow solid forms (e.g. tablets).

• Masks bitter tastes of medications effectively compared to solutions.

• High surface area aids rapid drug dissolution in gastrointestinal tract.

• Suitable for substances that hydrolyze in liquids, allowing for stable formulations (e.g. oxytetracycline can be utilized as an oral suspension).

Disadvantages of Oral Suspensions

• Sedimentation: Issues arise due to the settling of particles:

  • Caking/Claying: Deflocculated sediment forms a dense mass that’s hard to redisperse.

  • Flocculated Sedimentation: Loose cakes that are easier to redisperse but still lead to dosing inaccuracies.

• Hydrolytic degradation occurs over time, especially in the presence of moisture.

• Ostwald ripening can alter particle size distribution adversely, complicating formulations.

Particle Behaviour in Suspensions

• Aggregation and Coagulation:

  • Aggregation results in the collection of particles into groups.

  • Coagulation leads to strong attractive forces forming compact, hard aggregates that are difficult to disperse.

• Two Types of Sedimentation:

  • Flocculated Suspensions: Fast sedimentation with a discernible cloudy sediment and easy redispersion.

  • Deflocculated Suspensions: Slow sedimentation; compact sediment's challenging to resuspend and forms over long durations.

Measurement of Sedimentation

• F-value: Degree of sedimentation calculated as:
  $F = \frac{V<em>S}{V</em>T}$

  • Where:

  • $V_S$ = ultimate apparent volume of sediment

  • $V_T$ = total volume of suspension

  • Higher F-values indicate flocculated systems.

• b-value: Degree of flocculation calculated:
  $b = \frac{F}{F^\prime}$

  • Where:

  • $F$ = ultimate sedimentation volume of flocculated suspension

  • $F^\prime$ = ultimate sedimentation volume of deflocculated suspension.

Formulation Considerations

• Particle Size: Fine particle size slows sedimentation; a narrow size distribution is preferred to avoid Ostwald ripening.

• Hydrophilic Colloids: Help in promoting wetting of hydrophobic particles and providing suspension stability.

• Viscosity: Increasing viscosity of the continuous phase slows sedimentation

  • Non-Newtonian fluids play a role in stabilizing suspensions.

Typical Suspending Agents

• Examples of natural and synthetic agents:

  • Natural: Stratified polysaccharides (e.g. acacia, tragacanth).

  • Synthetic: Poly(acrylic acid), poly(vinyl-pyrrolidinone).

  • Minerals: Bentonite, magnesium aluminium silicate.

• Usage of these agents varies based on the need for viscosity and maintaining stability.