Dispersed systems 1

• Disperse system


  One phase (disperse phase) distributed in a second phase (continuous phase)
• Common pharmaceutical disperse systems

  • Suspension
  • Gel
  • Emulsion
  • Micellar system
  • Liposomal system
  • Aerosol
  • Foam
  • Solid dispersion
• Continuous phase


  The phase that the disperse phase is distributed in
• Disperse phase


  The phase that is distributed in the continuous phase
• Drug distribution in pharmaceutical disperse systems

  • One phase composed entirely of drug molecule
  • Drug molecule is dissolved in one phase of disperse system
  • Upon mixing with second immiscible phase a two phase system is formed
  • Drug molecules can partition into the second phase depending on the solubility of the drug in the second phase (revise logP)
  • Partitioning results in changes in chemical composition of both phases and can alter drug solubility in both phases which can further influence partitioning
• Partitioning


  • Drug molecules moving from the oil phase to the water phase
  • Oil molecules moving into water phase
  • Water molecules moving into oil phase
• A liquid in liquid dispersion

  • Emulsion
• Colloidal vs Coarse Disperse Systems

  • Colloidal (1 nm to 1 µm)
  • Coarse > 1 µm
  • Scatter light
  • Exhibit Brownian movement
  • Exhibit sedimentation
  • Pass through semi permeable membrane
  • Diffuse
  • Molecular disperse system i.e. solutions (< 1 nm)
• Colloidal dispersions do not contain particles of >1 um diameter, do not sediment very easily, do scatter light, do exhibit Brownian motion, and cannot pass through a semipermeable membrane
• Lyophilic (solvent loving)


  Molecules of the disperse phase has similar attraction for molecules of the continuous phase as they have for themselves
• Lyophobic (solvent hating)


  Disperse phase of lyophobic dispersion has little or no molecular attraction for the continuous phase
• Amphiphilic (has both lyophobic and lyophilic segments in same molecule)


  Molecules with amphiphilic behaviour in water contain a hydrophobic 'tail' and hydrophilic 'head'
• The opposite of lyophilic is lyophobic
• Lyophilic colloidal systems


  • Molecules of the disperse phase has similar attraction for molecules of the continuous phase as they have for themselves
  • If the disperse phase is in water then the colloids are referred to as hydrophilic colloids
  • E.g. is water-soluble high molecular weight molecules (proteins and peptides)
  • Spontaneous dispersion in water in time and thermodynamically stable
  • Due to high molecular weight and dimensions greater than 1 nm some macromolecules (protein and peptides) exhibit colloidal properties, however are classed as a molecular dispersions or solutions
• Lyophobic colloidal systems


  • Disperse phase of lyophobic dispersion has little or no molecular attraction for the continuous phase
  • Oil in water colloidal dispersion
  • Will not form spontaneously, energy needs to be added by strong agitation
  • Once agitation stops then the oil droplets will start to aggregate and coalesce with time
  • They are not thermodynamically stable
  • Will rearrange themselves to minimise contact area between dispersed and continuous phase
• Amphiphilic colloidal systems


  • Amphiphilic molecules in aqueous phase will orientate so that exposure of hydrophobic segment to aqueous phase is minimised
  • Also known as surfactants as they generally reduce surface tension
  • At low concentration molecules will distribute with hydrophilic head in water and tails sticking out in the air
  • At CMC (critical micelle concentration) they will for micelles
• Coarse dispersions (> 1 µm)

  • Molecules in disperse phase have little molecular attraction for continuous phase (similar to lyophobic colloidal dispersions)
  • Always lyophobic = thermodynamically unstable
• Physical stability of dispersed systems


  • Describes the ability of the disperse phase to remain uniformly dispersed in continuous phase
  • Uniformity of drug dispersion ensures patient receives same amount of drug each time a certain volume is administered
  • Higher concentrations or lower concentrations can be administered if an unstable suspension is not shaken up
• Kinetic properties of disperse systems

  • Brownian motion: Random movement, collisions between dispersed species and also between dispersed species and continuous phase, only seen with molecular and colloidal dimensions, influenced by viscosity
  • Sedimentation: Particles in suspension are subject to gravity and drag force, one of the phases needs to move
• Drag Force (FD)


  F_D = 1/2 C_D * A * ρ * v^2

  C_D - drag coefficient (viscosity of the medium, shape of body and surface roughness of body)

  A - cross sectional area perpendicular to direction of object's movement

  ρ - density of fluid medium

  v - velocity of object relative to fluid medium
• Stokes' equation


  v = (2/9) * (ρ_p - ρ_0) * g * r^2 / η

  v - velocity of a spherical particle with radius r

  ρ_p - density of disperse phase

  ρ_0 - density of liquid

  g - acceleration due to gravity

  η - viscosity of liquid
• Limitations of Stokes' equation: only applies if there is parallel movement of liquid or gas to falling object (suspension) (not inhalers), particles settle independently from each other and do not aggregate, applies to diffusible and indiffusible solids
• A colloidal particle in suspension will be displaced more by Brownian motion if the viscosity of the continuous phase is lower
• For coarse suspensions, drag force can reduce sedimentation
• Background reading: The physicochemical basis of pharmaceuticals. Moynihan and Crean Pages 156 - 192, Aulton's Pharmaceutics: The design and manufacture of medicines. Aulton Pages 435 – 464 (4th edition) for reference only!