Oral Suspensions

Disperse Systems

Definition: Two-phase heterogeneous system with an insoluble or immiscible dispersed phase in a continuous phase.

Classification by particle size:

  • Molecular dispersions: < 1 nm (e.g. glucose solution)

  • Colloidal dispersions: 1 nm to 1 μm (e.g. microemulsions, nanoparticles)

  • Coarse dispersions: > 1 μm (e.g. suspensions, emulsions)

Pharmaceutical Suspensions

Definition: A liquid disperse system with particles distributed in a liquid vehicle.

Classification: Coarse or colloidal dispersion (commonly 0.1 to 10 μm).

Appearance: Not optically clear; appears cloudy.

Reasons for Formulating Oral Suspensions

  • To deliver poorly water-soluble drugs.

  • To mask bitter taste.

  • To increase drug stability.

  • To achieve controlled or sustained drug release.

Flocculated vs. Deflocculated Suspensions

Flocculated System:

  • Particles form floccules due to Van der Waals forces.

  • Sediment is large; redispersion is easy.

  • Controlled flocculation prevents caking.

  • Induced by reducing surface charge (zeta potential) using surfactants and ionic salts.

Deflocculated System:

  • Particles are uniformly dispersed; may settle slowly, creating a difficult-to-re-suspend sediment.

  • Not ideal for pharmaceutical formulations.

Comparative Properties of Flocculated and Deflocculated Suspensions

Property

Flocculated

Deflocculated

Particles

Form loose aggregates (flocs)

Exist in separate entities

Sedimentation Rate

Rapid

Slow

Sediment Structure

Scaffold-like loose

Compact

Redispersion

Easy

Difficult

Supernatant Liquid

Generally clear

Cloudy

Controlling Stability of Suspensions

Ideal: Solid materials should be monodispersed and evenly suspended.

Suspensions are inherently unstable; random particle motion leads to aggregation.

Desired Properties for Uniform Dose:

  • Slow settling of particles.

  • Readily and uniformly re-dispersible.

  • Consistent particle size over time.

  • Appropriate viscosity for easy pouring.

Particle Movement in Suspensions

Influenced by:

  • Brownian Motion: Moves small particles (< 2 μm) irregularly, aiding homogeneity.

  • Gravity: Affects larger particles and their sedimentation patterns.

  • External Agitation: Shaking enhances re-dispersion.

Sedimentation

Downward movement due to gravity; critical for suspension success.

Optimal Sedimentation Pattern:

  • Slow sedimentation: favorable for deflocculated systems.

  • Reversibility: required for reproducible dosing in flocculated systems.

Impact of Particle Size on Sedimentation

Larger particles experience significant gravity effects.

According to Stokes’ Law, sedimentation velocity is proportional to particle size.

Controlling Sedimentation: Strategies

  • Size Reduction: Enhances diffusion; improves suspension stability.

  • Medium Density Increase: E.g., adding dextrose.

  • Medium Viscosity Increase: E.g., using hydroxypropyl methylcellulose (HPMC).

Zeta Potential

Measures electrostatic repulsion between particles at the slipping plane.

Affects suspension stability; lower zeta potential increases flocculation risk.

High zeta potential promotes particle repulsion and stability.

Role of Excipients

Impact on Electrical Double Layer:

  • Ionic salts increase mobile charge; can alter particle charge at varying concentrations.

  • Surfactants: Reduce interfacial tension to enhance suspension stability.

Common Excipients:

  • Sweeteners (e.g. saccharin, acesulfame potassium) improve palatability but must consider dental health implications.

  • Preservatives (e.g. sorbic acid, parabens) prevent microbial growth.

  • Buffers maintain pH and affect flocculation.

  • Suspending agents (e.g. HPMC, sodium alginate) reduce sedimentation.

Chemical Stabilizers and Wetting Agents

Stabilizers (e.g. antioxidants ascorbic acid at 0.2%w/v.) maintain chemical stability of drugs.

Wetting agents reduce interfacial tension and improve drug distribution.

Example Products

Augmentin® 125/31 SF Suspension: Contains amoxicillin, clavulanic acid, xanthan gum, HPMC, with a shelf life of 2 years.

Gavison® Original: Contains sodium alginate, sodium bicarbonate, and others, with a 2-year shelf life and storage requirements.