Medicinal Suspensions Notes

Learning Outcomes

• Definition of Pharmaceutical Suspension:

  • A pharmaceutical suspension is a dispersion of fine, insoluble, solid particles (disperse phase) within a liquid (continuous phase or dispersion medium).

• Properties of Well-Formulated Suspensions:

  • Disperse phase particles should be small and uniformly sized with minimal settling.

  • Settled particles should not form a compact, difficult-to-dispersed sediment.

  • Each dose should contain a consistent amount of the suspended solid drug.

  • Should have an agreeable odor, color, taste, and texture (avoiding a gritty feel).

  • Continuous phase should prevent microbial growth during storage.

• Factors Causing Instability in Suspensions:

  • Sedimentation can lead to issues like deflocculated or flocculated sedimentation, which may result in inaccurate dosing.

  • Hydrolytic degradation of drugs in the presence of water (e.g., tetracyclines).

  • Ostwald Ripening: smaller particles dissolving and re-crystallizing onto larger particles, altering mean particle size distribution.

• Quantifying Instabilities in Suspensions:

  • F-value: Represents the degree of sedimentation, quantified as:
    $F = \frac{V<em>S}{V</em>T}$
    where:

  • $V_S$ = ultimate apparent volume of sediment

  • $V_T$ = total volume of suspension.

  • b-value: Ratio related to volume of flocculated sediment versus deflocculated sediment, quantified as:
    $b = \frac{F}{F^\prime}$
    where:

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

Advantages of Well-Formulated Suspensions

• Facilitates administration in patients with difficulty swallowing pills.

• Masks the bitterness or unpleasant taste of solid dosage forms.

• High surface area of fine suspensions promotes rapid dissolution in the gastrointestinal tract.

• Allows for fast action of adsorbing compounds and neutralizing agents like antacids.

• Can include drugs that would degrade in liquid solutions, such as hydrolyzing agents.

Disadvantages of Oral Suspensions

• Sedimentation Problems:

  • Deflocculated sediment forms a firm mass that is hard to resuspend (caking).

  • Fast sedimentation forming a loose cake that can be easily resuspended (flocculation) can cause dosing inaccuracies.

• Hydrolytic Degradation: The presence of water can lead to stability issues despite the drug being classified as insoluble.

Sedimentation Characteristics

• Sedimentation Rate Relation:

  • Settling velocity of particles is described by Stokes' Law:
    $v = \frac{(r_s - r)g a^2}{9 \eta}$
    where:

  • $v$ = velocity of sedimentation

  • $r_s$ = density of the particle

  • $r$ = density of liquid

  • $g$ = gravitational acceleration

  • $a$ = particle radius

  • $\eta$ = kinematic viscosity of the liquid.

Particle Size and Stability

• Suspensions require a small and uniformly sized particle distribution to prevent rapid sedimentation and Ostwald ripening.

• Minimum Size Recommendations: Particle sizes over 5 mm can result in a gritty texture.

Methods to Improve Stability

• Utilize hydrophilic colloids to coat solid particles enhancing wetting properties and promoting stability.

• Increase the viscosity of the continuous phase to slow the rate of sedimentation, using suspending agents like hydrophilic colloids, synthetic polymers, and natural clay minerals.

• Examples of suspending agents include:

  • Hydrophilic Colloids: Acacia, tragacanth, gelatine, alginates.

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

  • Natural Clay Minerals: Bentonite, magnesium aluminum silicate.

Conclusion

• Understanding the design and formulation of medicinal suspensions is crucial for ensuring effective dosage and patient compliance. Key factors like particle size, stability, and formulation techniques play a significant role in the success of suspensions as pharmaceutical products.