suspensions

• define a suspension

  pharmaceutical suspensions are made of solid particles with low solubility dispersed in an other phase e.g. an aqueous liquid
• what are the characteristics of a suspension?

  • Particles (dispersed phase) size from 0.5 mm to 100mm
  • High concentrations of drugs are used - suspensions can provide a large amount of the drug.
• examples of when suspensions are used...

  • unpalatable soluble drugs given in an insoluble form to hide the unpleasant taste.
  • lotion used to deposit fine powder on the skin surface.
  • slow release formulation to give prolonged effect
• what are the desirable qualities of a suspension?

  • Particles in the pharmaceutical suspensions should settle (positively sediment at the bottom) slowly.
  • Sediments should disperse easily on shaking to provide the patient with a representative sample
  • No caking or clumping should be observed
  • Should be pourable from the bottle and will flow through a needle. They should spread easily on the skin without running away.
  • The electrical properties of suspensions follow the same as for other colloidal dispersions.
• so technically, suspensions should...

  • Be easily made by standard methods and equipment
  • No change in the crystal size or form during storage
  • Not support microbial growth
  • Be chemically stable
  • Give the required bioavailability
• stability of suspensions;

  They are prepared with solids and a liquid thus gravity will influence behaviour - it is subject to Strokes law and DLVO. Solid particles will always eventually sediment. This can lead to caking.
• larger particles will sediment faster than smaller ones.
• what is caking?

  Particles sediment over time. The particles at the bottom are gradually compressed by the weight of those above: so energy provided by gravity is sufficient enough to overcome the primary maximum (repulsive forces) and form an irreversible interaction at the primary minimum.
• after caking, can particles be re-dispersed?

  No. No matter how much you shake.
• define a floc or flocculate

  A cluster of particles held together in a loose open structure (i.e. two particles are attached via Van der Waal forces for a while and then separate). Flocs are spontaneously formed and broken down.
• what is the influence of DLVO theory concerning flocculation?

  It means that a moderately deep secondary minimum area is required for their formation (decrease of repulsion potential)
• what are the characteristics of a flocculated suspension?

  • Sediments faster - sediments well and sediment contains voids (spaces/gaps)
  • High volume
  • Rapidly obtained
  • Easy to re-disperse
  • No problems from caking

  
• what occurs in a deflocculated suspension?

  • particles don't form loose open aggregates (flocs)
  • particles sediment independently
  • the potential of repulsion is high so particles are often separated
  • pressure on particles in sediment may overcome the primary maximum (repulsion forces) energy barrier to become irreversibly bound together (caking/aggregation)
• what are the characteristics of deflocculated suspensions?

  • sediment compact with few voids
  • sedimentation is slow
  • difficult to re-disperse
  • susceptible to caking

  
• are pharmaceutical suspensions usually flocculated or deflocculated?

  they are partially flocculated (some particles will sediment at the bottom faster) and partially deflocculated (particles stay in suspension for longer - provide patient with a representative sample of dose)
• ways to control flocculation

  via ions or the addition of polymers
• how does the addition of polymers control flocculation?

  Linear branched chains from a gel-like network within the system become adsorbed on the dispersed particles - protective colloids.
• when can the addition of polymers result in a deflocculated system?

  When during manufacture the blending is excessive. This is because it can inhibit cross-linking between adjacent particles.

  Also, a high concentration may have a similar effect.
• pharmaceutical considerations with suspensions; wetting properties

  Wetting properties and therapeutic agents - insoluble therapeutic agents need to be wetted to ensure reduction of interfacial tension and thus risk of aggregation.

  Importance to use surface active agents (surfactants)
• pharmaceutical considerations for suspensions; Particle size

  The size of the particle must be controlled either by chemical (controlled precipitation) or physical (milling) methods. Smaller particles have a higher dissolution rate than larger ones but crystallisation may happen at the surface of larger particles.
• which type of emulsion may also suffer from Ostwald ripening?

  water in oil
• why is flocculation essential in suspensions?

  for the redispersion of solid particles.
• The polydispersity of suspended particles often leads to what?

  Ostwald ripening which ultimately results in larger particles.
• how does the concentration of ions affect the flocculation process of a bismuth subnitrate suspension?


  By adjusting the concentration of dibasic potassium phosphate, the suspension undergoes controlled flocculation leading to the formation of larger flocs. The secondary minimum contributes to the formation of flocculated particles.
• what is the effect of the type of ion on controlling flocculation?

  Charge. The ability to aggregate hydrophobic colloids, thus inducing flocculation, depends on the charge number of the ion and the type of ion.
• what are common ions used for inducing flocculation?


  sodium salts of acetates, phosphates and citrates
• an example of when ions affect the flocculation of a solution...


  With AgI solutions, faster flocculation occurs with ions of higher charge.
• examples of polymers used to control flocculation...


  starch alginates, cellulose derivatives, tragacanth, carbomers and silicate
• what is Ostwald ripening?

  Related to the difference in dissolution between small and large particles. Large particles grow at the expense of smaller ones over time.
• how does Ostwald ripening occur in suspensions?

  This occurs due to the differential solubility of particles of different sizes and the tendency for smaller particles to dissolve and redeposit onto larger ones. Smaller particles are more energetically favourable to dissolve. Leads to a narrowing of the size distribution within the suspension.