Pharmaceutical Science: Coarse Dispersion Quiz

Heterogeneous System - Coarse Dispersion

• Liquid preparations contain undissolved or immiscible drugs distributed throughout a vehicle.
• The dispersed substance is the dispersed phase.
• The vehicle is the dispersing phase or dispersion medium.
• Suspensions: Solid materials are insoluble in the dispersion medium.
• Emulsions: The dispersed phase is a liquid immiscible with the liquid dispersion phase.
• Aerosols: The dispersed phase can be small air bubbles in a solution or emulsion.
• Particle size of coarse dispersions: 10-50 µm.
• These include suspensions and emulsions.
• Particle size of fine dispersions: 0.5-10 µm (collodial range)
• Fine dispersions include Magmas and gels.
• Colloidal dispersions are in the colloidal range.
• Complete and uniform redistribution of the dispersed phase is essential for accurate administration of uniform doses.
• This is achieved through moderate agitation.

Suspensions

• Contain finely divided drug distributed somewhat uniformly throughout a vehicle.
• The drug has minimal solubility in the vehicle.
• Pharmaceutical suspension: Coarse dispersion of insoluble solid particles in a liquid medium.
• Particle diameters are generally greater than 0.1 µm.
• Some suspensions are available in ready-to-use form, already dispersed in a liquid vehicle, with or without stabilizers and additives.
• Some suspensions are available as dry powders intended for suspension preparation in a liquid vehicle.
• Often contain the drug, suitable suspending & dispersing agents for dilution and agitation in purified water.
• Some drugs (e.g., antibiotics) are unstable in an aqueous medium and are supplied as dry powder mixtures for reconstitution.

Reasons for Suspensions

• Certain drugs are chemically unstable in solution but stable when suspended.
• This ensures chemical stability for liquid therapies, particularly with infants, children and the elderly.
• The disagreeable taste of certain drugs can be overcome when administered undissolved as an oral suspension.
• Example: Erythromycin estolate (less water-soluble ester form of erythromycin) is used in oral suspension to increase palatability.
• Usually aqueous preparations, flavoured, and sweetened to suit the patient.

Features Desired in a Pharmaceutical Suspension

• Therapeutically active, chemically/physically stable, and aesthetically appealing.
• Remain homogenous for a period of time.
• Settle slowly and redisperse readily upon gentle shaking.
• Particles must not form a hard cake at the bottom.
• Particle size should remain fairly constant throughout time.
• Should pour readily and evenly from the container.

Sedimentation Rate of the Particles of a Suspension

• Stokes' Law Equation: dx/dt = d² (ρ₁ - ρ₂)/18η
• Factors involved in settling rate:
• 'dx/dt' is the rate of settling.
• 'd' is the diameter of the particle.
• 'ρ₁' is the density of the particles.
• 'ρ₂' is the density of the medium.
• 'g' is the gravitational constant.
• 'η' is the viscosity of the medium.
• Factors affecting physical stability: particle diameter, density, viscosity of the medium.
• Greater particle density leads to faster sedimentation.
• Aqueous vehicles commonly used, so particle density is usually greater than the vehicle density, which is desirable.

• Viscosity of the medium may be increased to reduce sedimentation rate.

Sedimentation in Different Systems

• In flocculated systems, the flocs tend to settle together, with a distinct, clear boundary between the sediment and the supernatant, which is clear.
• In deflocculated systems, sedimentation occurs more slowly, with no distinct boundary between, the sediment and supernatant, which remains turbid ("cloudy") for a longer period.

Sedimentation Parameters

• Sedimentation volume (F) is the ultimate volume of sediment (V_u) divided by the original volume of the suspension (V_o)
• If V_u is smaller than V_o , F = 0.5
• If V_u is equal to V_o , F = 1
• It is possible for F to be greater than 1.

Evaluation of Suspensions

• Techniques to screen initial preparations & compare products.
• Sedimentation volume (F).
• Redispersability (number of inversions necessary to redisperse the sediment).
• Rheological characteristics (flow properties).

Suspension Components

• Insoluble drug
• Vehicle (suspending medium)
• Wetting agent
• Flocculating/suspending agent
• Additives to control flow behavior
• pH regulators
• Other additives

Wetting Agents

• Some insoluble solids are easily wetted by water and disperse readily in the aqueous phase with little agitation.

• Most require additional wetting agents.

• To ensure adequate wetting, interfacial tension between the solid and the liquid must be reduced.

• Wetting agents:
  1. Surface-active agents (e.g., polysorbates, sorbitan esters, sodium lauryl sulfate, sodium dioctylsulphosuccinate).
  2. Hydrophilic colloids (e.g., acacia, alginates, bentonite).
  3. Solvents (e.g., alcohol, glycerol, propylene glycol).

Flocculating Agents

• Achieved by a combination of particle size control, electrolytes to control zeta potential and polymers to enable crosslinking between particles.
• Electrolytes: reduce the electric barrier between particles.
• Surfactants may neutralise surface charges.
• Polymers: form a gel-like network within the system to hold the dispersed particles in flocculated state.

Zeta Potential

• Zeta potential is related to electrostatic repulsion between the particles and colloidal stability.

Flocculating Agents

• Electrolytes

• Surfactants

• Polymers

• Alteration in pH of preparation to minimum drug solubility

Viscosity Modifiers (Suspending Agents)

• High disperse phase concentration, sufficient viscosity in absence of flocculating agent.
• Suspending agents used to increase apparent viscosity.
• Suitable materials are hydrophilic polymers.
• They entrap solid particles within their gel-like network to prevent sedimentation.

Suspending Agents

• 1. Polysaccharides (e.g., Acacia, Tragacanth, Alginates, Starch, Xanthan gum)
• 2. Water-soluble Celluloses (e.g., Methylcellulose, Hydroxyethylcellulose, Carmellose sodium, Microcrystalline cellulose)
• 3. Hydrated Silicates (e.g., Bentonite, Magnesium aluminium silicate, Hectorite)
• 4. Carbomers (e.g., carboxypolyethylene)
• 5. Colloidal silicon dioxide (Aerosil®)