Suspensions - AK

What is a pharmaceutical suspension?

A heterogeneous system where solid drug particles (dispersed phase, typically 0.1–10 µm) are suspended in a liquid vehicle (continuous phase, usually water). Unlike solutions, suspensions are optically cloudy due to light scattering by particles.

How do suspensions differ from solutions?

• Solutions: Homogeneous, molecular dispersion; optically clear; no sedimentation.

• Suspensions: Heterogeneous, particulate dispersion; cloudy; prone to sedimentation.

Why are suspensions used in pharmaceuticals?

or drugs with low aqueous solubility where solution formulations are impractical. Common routes: oral, topical, ophthalmic, parenteral (e.g., intramuscular).

What is the electrical double layer (EDL)?

A charged layer around particles in water:

1. Fixed (Stern) layer: Tightly bound counterions (e.g., H⁺ from H₃O⁺).

2. Diffuse (Gouy-Chapman) layer: Loosely bound counterions (e.g., Na⁺).

What is a zeta potential?

Potential at the shear plane between these layers; indicates stability.

How does pH affect particle charge?

Hydrophobic particles acquire negative charge in water due to OH⁻ adsorption (from H₂O autoionization). pH adjustments alter ionization of surface groups.

What factors affect the EDL thickness?

• Ionic strength: High ionic strength (e.g., NaCl) compresses the diffuse layer (↓ Debye length, 1/κ).

• Surfactants: Adsorb to particle surfaces, altering surface potential (ψ₀).

What does DLVO theory predict?

The balance between:

• Van der Waals attraction (Vₐ): Always negative (promotes aggregation).

• Electrostatic repulsion (Vᵣ): Positive (stabilizes suspension).

• Total interaction energy (Vₜ) = Vₐ + Vᵣ.

Describe the three interaction zones:

1. Primary minimum: Deep energy well → irreversible coagulation (bad).

2. Primary maximum: Energy barrier → deflocculation (risky if kinetic energy overcomes barrier).

3. Secondary minimum: Shallow well → reversible flocculation (ideal for suspensions).

How do additives impact DLVO behavior?

• Ionic excipients (e.g., NaCl): Compress EDL → deeper secondary minimum (promotes flocculation).

• Surfactants: Modify ψ₀ → may stabilize or destabilize.

What governs particle movement in suspensions?

• Diffusion (Brownian motion): Dominant for particles <1 µm (per Stokes-Einstein equation).

• Sedimentation (Stokes’ law): Dominant for particles >0.5 µm.

What is the sedimentation volume ratio (F)?

F=Vf​/V0​, where:

• VfVf​: Final sediment volume.

• V0V0​: Initial suspension volume.

• Flocculated systems: High F (~0.6), loose sediment.

• Deflocculated systems: Low F (~0.1), dense "cake."

How to control sedimentation?

• Reduce particle size (↓ r in Stokes’ law).

• Increase medium viscosity (↑ η, e.g., with polymers like HPMC).

• Match densities of particle and medium (e.g., add dextrose).

What is Ostwald ripening?

Growth of large particles at the expense of small ones due to temperature cycling:

1. High temp: ↑ solubility → small particles dissolve.

2. Low temp: ↓ solubility → drug precipitates on large particles.

• Solution: Use drugs with flat solubility-temperature profiles.

How does wetting affect stability?

Hydrophobic particles resist wetting → clump. Surfactants (below CMC) reduce interfacial tension → improve dispersion.

Why is flocculation preferred?

Flocculated systems:

• Sediment rapidly but are easily redispersed.

• Avoid irreversible caking (deflocculated systems).

List excipients and their roles:

How does sodium CMC affect suspensions?

• ↑ Viscosity → slows sedimentation.

• Releases Na⁺ → compresses EDL → may promote flocculation.

What are Key manufacturing challenges?

• Initial dispersion: Avoid caking (use high-shear mixing).

• Scale-up: Maintain uniform particle distribution.

• Packaging: Stirred hoppers to prevent settling during filling.

How to assess suspension stability?

• Sedimentation rate: Measure FF over time.

• Redispersibility: Shake and check uniformity.

• Particle size analysis: Ensure no Ostwald ripening.

What are the Requirements for oral suspensions?

• Palatable (flavors/sweeteners).

• Viscosity balance: Easy to pour but resists sedimentation.

What are the Requirements for ophthalmic suspensions?

• Sterile (aseptic preparation; cannot be filtered).

• Isotonic (~300 mOsm/kg), pH ~7.4.

• Particle size <10 µm to avoid irritation.

How does particle size affect dissolution?

Smaller particles ↑ surface area (per Noyes-Whitney equation) → faster dissolution → better bioavailability.

What is the Hamaker constant (A)?

Material-specific constant in VA=−Ar/12HVA​=−Ar/12H. Reflects van der Waals attraction between particles in a medium.

Why avoid surfactants above CMC?

Micelles solubilize drug → converts suspension into a colloidal dispersion, altering stability.

A suspension shows irreversible caking. Possible causes?

• Deflocculation: Particles in primary minimum.

• Inadequate surfactant: Poor wetting → aggregation.

• High ionic strength: Excessive EDL compression.

How to fix Ostwald ripening?

• Use a drug with minimal solubility-temperature dependence.

• Add polymeric stabilizers (e.g., PVP) to inhibit crystal growth.