Suspensions

What is a dispersed system?

A liquid preparation containing an undissolved or immiscible drug distributed throughout a vehicle.

What are the two phases of a dispersed system?

The dispersed phase is distributed throughout the dispersing phase or dispersion medium.

What is the dispersed phase?

The substance or phase distributed throughout the dispersion medium.

What is the dispersion medium?

The vehicle or external phase throughout which the dispersed phase is distributed.

What is a pharmaceutical suspension?

A dispersed system in which insoluble solid particles are uniformly dispersed through a vehicle by agitation and suspending agents.

What is the dispersed phase in a suspension?

Solid particles that have minimum solubility in the external phase.

What makes a suspension pharmaceutical?

One or more suspended particles are pharmaceutically useful or physiologically active.

What are the three general classifications of pharmaceutical suspensions?

Oral, externally applied (topical), and injectable (parenteral) suspensions.

How do suspensions differ from emulsions?

Suspensions contain solid particles; emulsions contain liquid droplets that are immiscible with the dispersion medium.

What are magmas and gels?

They are fine dispersions; magmas contain suspended inorganic solids such as bentonite magma.

What are coarse dispersions?

Dispersions containing relatively large particles, generally about 10–50 μm.

What are fine dispersions?

Dispersions containing particles approximately 0.5–10 μm.

What are colloidal dispersions?

Dispersions containing particles approximately 1 nm–0.5 μm.

Why must suspended particles redistribute uniformly after agitation?

Uniform redistribution is needed to ensure accurate administration of a uniform dose.

Why do most solid particles in suspensions settle?

They usually have a greater density than the dispersion medium.

What are the desirable qualities of a pharmaceutical suspension?

Slow settling, easy redispersion, no caking, uniform pouring, acceptable particle size, and suitable viscosity.

Why should a suspension have a slow sedimentation rate?

Particles should remain suspended long enough for an accurate dose to be measured.

Why must sediment be easily redispersed?

So the drug becomes uniformly distributed again before the dose is withdrawn.

Why should particle size remain unchanged during storage?

Changes can cause crystal growth, caking, altered dissolution, and instability.

Why should suspensions not be excessively viscous?

They must pour freely from a bottle or pass through a needle when required.

Why is small particle size desirable in suspensions?

It improves appearance, reduces gritty texture, affects settling, and can improve resuspendability and stability.

What factors are influenced by particle size?

Product appearance, settling rate, drug solubility, absorption, resuspendability, and overall stability.

Why can excessive particle-size reduction cause aggregation?

Very small particles have increased surface free energy and cohesion, encouraging agglomeration.

What happens when particles are reduced below about 10–50 μm?

Surface free energy increases, cohesion increases, moisture attraction increases, and particles may agglomerate.

Why can aggregated particles become difficult to wet?

Aggregates entrap air and behave like hydrophobic solids.

What methods can be used to reduce particle size?

Dry milling, wet milling, micro-pulverization, fluid-energy grinding, controlled precipitation, and spray drying.

What is dry milling used for?

It is an efficient method for producing fine particles before suspension manufacture.

What is wet milling?

Breaking up poorly wetted fine-particle aggregates using equipment such as colloid mills or homogenizers.

What is crystal growth in a suspension?

The growth of larger particles at the expense of smaller particles, which can alter particle-size distribution.

What is Ostwald ripening?

Growth of larger particles at the expense of smaller particles because particles of different sizes have different solubilities.

How can chemical stability of a suspension be improved?

Use a pH where the drug is least soluble and select a less-soluble drug form or salt.

Why does a suspended drug mainly decompose in solution?

The solid must gradually dissolve before the dissolved drug can undergo degradation.

What environmental factors can promote drug degradation?

Oxygen, light, and trace metals can initiate or catalyze degradation.

What is physical stability of a suspension?

A condition where particles do not aggregate and remain uniformly distributed, or can be easily redispersed after settling.

Why are fine dispersions of water-insoluble drugs thermodynamically unstable?

Their particles have high surface energy, creating a tendency for aggregation.

What are the two states of flocculation in suspensions?

Flocculated and deflocculated states.

What is a deflocculated suspension?

A suspension in which particles remain discrete and settle slowly but may form a tightly packed cake.

What is the main disadvantage of a deflocculated suspension?

Particles can form a hard sediment that is difficult or impossible to redisperse.

Why does caking occur in deflocculated suspensions?

Particles settle closely together, allowing physical bonding and bridges to form between particles.

What factors can aggravate caking?

Crystal growth and hydration effects at particle junctions can strengthen the sediment.

What is a flocculated suspension?

A suspension in which particles form loose aggregates called flocs.

Why are flocculated sediments easier to redisperse?

Flocs form a loose, open structure rather than a closely packed sediment.

Why does the supernatant become clear rapidly in a flocculated suspension?

Colloidal particles become trapped within the flocs and sediment with them.

What is the disadvantage of excessive flocculation?

Rapid clarification can compromise dose accuracy immediately after gentle shaking.

What is the ideal approach to suspension flocculation?

Partial flocculation, balancing slow settling with easy redispersion.

How does zeta potential affect suspension stability?

High zeta potential increases particle repulsion, while reducing it can promote controlled flocculation.

How do flocculating agents promote flocculation?

They reduce repulsive forces sufficiently for particles to form loose flocs.

What are primary flocculating agents?

Simple neutral electrolytes that induce attraction of particles into loose flocs.

Which electrolytes can induce flocculation of weakly charged particles?

Small concentrations of sodium or potassium chloride can induce flocculation.

What ions may be required for highly charged polymers or polyelectrolytes?

Water-soluble divalent or trivalent ions such as calcium salts, alums, sulfates, citrates, and phosphates.

What are polymeric flocculating agents?

Linear or branched molecules that form a gel-like network and adsorb onto particles, maintaining flocculation.

Which polymers are examples of structured flocculating agents?

Starch, alginates, and carbomers.

How do structured vehicles help suspensions?

They form a network, modify viscosity, and help maintain particles in a flocculated state.

What are wetting agents?

Surface-active agents that help liquid wet and disperse solid particles.

Which surfactants are examples of wetting agents?

Polysorbates and sorbitan esters; docusate sodium may also be used.

What is an important limitation of excessive wetting agent?

Excessive amounts may cause foaming or affect the product's taste or odor.

What concentration of polysorbate 80 is specified in the lecture?

Not more than 0.1–0.2% w/v.

How can electrolytes or ionic surfactants promote flocculation?

They reduce repulsive forces enough to allow charged particles to aggregate.

What are deflocculants and dispersing agents?

Agents that disperse particles without appreciably lowering surface/interfacial tension like surfactants.

Which deflocculant is approved for internal use according to the lecture?

Lecithin or lecithin derivatives.

How can viscosity be increased in a suspension?

Add viscosity enhancers such as tragacanth or cellulose derivatives, or use structured vehicles.

Which structured vehicles are mentioned for increasing viscosity?

Bentonite, alginates, and carbomers.

How does increasing vehicle viscosity affect suspendability?

It helps slow particle settling by increasing resistance to particle movement.

What role does Stokes' equation have in suspension formulation?

It relates particle settling velocity to factors such as particle size, density difference, viscosity, and gravity.

Which factors should formulation control to reduce sedimentation according to Stokes' principle?

Reduce particle size and density difference and increase vehicle viscosity.

What is the main formulation aim for a suspension?

To keep insoluble solid particles in a state of suspension.

What are the main approaches used to improve suspendability?

Control particle size, increase vehicle viscosity, use wetting agents, and use structured vehicles.

What is the small-scale compounding sequence for a suspension?

Size-reduce, sieve and weigh solids; add suspending agent; triturate with part of vehicle to a smooth paste; then gradually incorporate the remaining vehicle.

Why are solids triturated into a smooth paste before dilution?

To produce a uniform, lump-free dispersion before adding the remaining vehicle.

When should glycerol or syrup be used during compounding?

They can be used with the powder to form the initial paste when included in the formulation.

How are soluble solids incorporated into a suspension?

Dissolve them in the remaining vehicle and add gradually, triturating to a smooth consistency between additions.

What equipment can be used for particle-size control during preparation?

A mortar and pestle, colloidal mill, or homogenizer.

How can poorly wetted solids be removed from a prepared slurry?

Pass the slurry through a fine wire mesh or use a colloidal mill or gentle impeller mixing.

What quality tests are used to evaluate suspension appearance and acceptability?

Color, odor, and taste are assessed, especially for oral suspensions.

What can a variation in suspension color indicate?

Poor distribution and/or differences in particle size.

What can changes in taste indicate?

Changes in particle size, crystal habit, and subsequent particle dissolution.

What can changes in odor, color, or taste indicate?

They may indicate chemical instability.

How is viscosity evaluated in pharmaceutical suspensions?

A Brookfield viscometer can evaluate rheological properties, stability, and settling behavior.

Why is suspension density measured?

Density is an important parameter; decreased density may indicate entrapped air.

How is suspension density measured?

Using precision hydrometers on a well-mixed, uniform suspension at a specified temperature.

How should pH be measured in a suspension?

At a specified temperature after settling equilibrium is reached to reduce pH drift and electrode coating.

What is the purpose of freeze-thaw testing?

To evaluate the physical stability of a suspension under temperature stress.

What is the usual storage temperature range stated in the lecture?

Approximately 15–30 °C; suspensions are not normally designed for temperature extremes.

How is drug-content uniformity evaluated?

Sample a unit-of-use volume or well-mixed suspension from the top, middle, and bottom.

What does dissolution testing assess in a suspension?

Drug release into the gastrointestinal tract.

How is dissolution testing of suspensions performed in the lecture?

A known suspension amount is placed in a suitable membrane pouch and tested using USP Method 1 Paddle Apparatus.

What can photon correlation spectroscopy measure?

Particle size, size distribution, concentration, molecular weight, polydispersity, particle shape, and aggregation.

What sedimentation properties can be tested?

Sedimentation rate, sediment volume, and resuspendability.

What additional quality procedures can be performed?

Potency assays, preservative-effectiveness testing, and container-closure compatibility.

What packaging is appropriate for pharmaceutical suspensions?

A container appropriate for the administration route and characteristics of the formulation.

Why should thick suspensions use wide-mouth containers?

The wider opening facilitates removal and handling of viscous suspension.

How should suspensions be stored to protect physical stability?

Store appropriately in a cool place; refrigerate when directed and do not freeze.

Why should suspensions be protected from extreme temperature changes?

Temperature extremes can adversely affect their physical stability.

What should the patient do before administering a suspension?

Gently shake it sufficiently to redistribute the suspended particles and obtain a uniform dose.