Disperse Systems: Suspensions 7

Question 1

Suspensions

Answer 1

• Is a Coarse Dispersion
  
  • 500-1000nm (1mm)
  • Visible by microscopy or even naked eye
    
    • 400-700nm = wv of light (visible)
• Consist of Solid Particles dispersed in a Liquid Medium
  
  • ​except aerosols
    
    • –> in gas medium
• ​​Brownian motion is observed for smaller particles

Question 2

Suspension Dosage Forms

Answer 2

• Oral Suspensions
  
  • ​allow delivery of large doses of water insoluble solids
  • typically 10% w/v for easy to swallow liquids
• Dermatological Products
• Parenteral Administration
  
  • particle size matters

Question 3

Desired Properties of

Oral Suspensions

Answer 3

• Should not settle rapidly
  
  • ​not form a hard cake
  • Should be readily dispersed to form a uniform mixture with shaking
• ​Not too viscous
• Physically Stable
• These properties should NOT CHANGE during storage:
  
  • ​Particle size distribution
  • specific surface area
  • crystallinity / solid polymorphicform

Question 4

Suspension Agglomeration

2 distinct ways

Answer 4

• Flocculation
  
  • ​form loose, fluffy conglomerate
    
    • held by weak VDW forces
  • Surface area is slightly reduced
  • Sometimes good
• Aggregation
  
  • _​_compacted solid cake
    
    • maximum interparticle surface-surface contact
  • surface area is DRASTICALLY reduced
  • Always Bad

Question 5

Suspension Flocculation

Answer 5

• VDW attraction
• Forces of Repulsion are from double layer zeta potential
• LOW ZETA POTENTIAL
  
  • ​Weak atraction results in flocculation
  • 100-200nm (small energy well)
  • –> only MINIMAL shaking will disrupt the floc
• Sedementation due to gravity will occur
  
  • But a high energy barrier due to high zeta potential resists further aggregation due to gravity
  • Easily RESUSPENDED

Question 6

Suspension Aggregation

Answer 6

• Form hard cake under gravity
• No energy well (dip), when system is Deflocculated
  
  • Can not form a floc
• High Zeta Potential
  
  • ​particles can approach more closely
  • high surface to surface contact
    
    • –> results in Aggregation
• ​​Sedementation
  
  • difficult to RESUSPEND due to hard cake

Question 7

Velocity of Sedementation (V)

Answer 7

• Expressed by Stoke’s Law
  
  • ​​​for dispersions containing 0.5%-2% suspended solids
• Positive V = settles to the BOTTOM (more sedementation)
• V depends on:
  
  • diameter of particle
  • Difference of density of particle/medium
  • Gravity accelleration
  • INVERSELY RELATED TO VISCOSITY
    
    • ​​​Increasing velosity –> Decreases Velocity of sedementation

Question 8

Brownian Movement

on

Sedementation

Answer 8

• Brownian motion COUNTERACTS sedementation
  
  • ​for particles <5um diameter
  • depends on density and viscosity of medium
• As Viscosity increases -> Brownian Motion decreases
• Ideally:
  
  • Density of Medium = Density of Particles
    
    • NO SEDEMENTATION

Question 9

Calculating Degree of Flocculation

beta

Answer 9

Compare the Volume of sedement (F) for the floc

with

the Volume of the sedement (f infinity) that would have been obtained with COMPLETE deflocculation

Question 10

Approaches to develop

Suspension Dosage Forms

Answer 10

• Structured Vehicle, used as the dispersing medium
  
  • ​Colloidal dispersions of HydroPHILIC polymers in water
  • polymers have negative surface charge
  • polymeric lyophilic colloid has HIGH VISCOSITY
  • Example = KETCHUP
    
    • Vigorous shaking –>decrease Viscosity
    • Vicosity is effected by SHEAR FORCES
• ​Design the formulation to promote CONTROLLED FLOCCULATION

Question 11

Wetting of Particles

Answer 11

• Particles need to be thoroughly wetted by the dispersion medium
  
  • ​HYDROPHILIC substances are EASILY WETTED
  • ​HydroPHOBIC substances are DIFFICULT to wet
    
    • large CONTACT ANGLES
    • ​​initially covered by air molecules
      
      • Adsorbed to the surface
  • ​Surfactants are often added to:
    
    • promote wetting
    • INFLUENCE FLOCCULATION
      
      • Need enough surfactant or else –> deflocculate

Question 12

Levigation

Answer 12

• Process of grinding a substance under moist conditions
  
  • Mortar & Pestle
• Purpose is for particles to be UNIFORMLY COATED WITH THE LIQUID USED FOR LEVIGATION
  
  • ​some particle size reduction may occur
• ​Always requires a liquid
• Used to WET particles for SUSPENSIONS
  
  • ​Hydroscopic hydrophilic solvents are used
    
    • alcohol / glycerol / propylene glycol

Question 13

Trituration

Answer 13

• Process of grinding two or more solids
• Purpose is to REDUCE PARTICLE SIZE
  
  • and to uniformly mix the two particles
• NO LIQUID

Question 14

Controlling Flocculation

Answer 14

• We DO NOT want systems to DEFLOCCULATE
• Structured Vehicles help prevent content uniformity
  
  • Retart sedementation of the floc
• ELECTROLYTES acts flocculating agents by
  
  • DECREASING ZETA POTENTIAL
  • and forming salt bridges that link particles in a loose structure
• CONCENTRATION of electrolytes is CRITICAL
  
  • Too low –> zeta is too HIGH –> deflocculation
  • Too MUCH –> zeta potential reverses and becomes large
  • IDEALLY WANT ZETA POTENTIAL CLOSE TO ZERO

Question 15

Rheologic Considerations

Relating to flow

Answer 15

• Seen with Plot of Shear Rate vs Sheer Stress
• We want PSEUDOPLASTIC FLOW
  
  • NONLINEAR
  • Steep RISE at higher stress
  • High viscosity at low shear force
  • low viscosity at HIGH shear force
    
    • ​ex. Tragacanth / Sodium alginate
• ​**Do not want NEWTONIAN FLOW
  
  • ​straight line
  • ex. GLYCERINE

Question 16

Thixotropy

Answer 16

• Become Less and Less Viscous
  
  • ​when Stirred
• ​BUT become more and more Viscous
  
  • ​upon SITTING
• ​THINK KETCHUP AND YOGURT
  
  • Examples of thixotropic Gels
• SHOW PSEUDOPLASTIC BEHAVIOR
  
  • ​good suspending agents
  • CMC + MIcro Bentonite

Question 18

Physical Stability of Suspensions

Answer 18

• HEATING
  
  • ​Cause suspensions to FLOCULATE
    
    • esp those w/ NONIONIC surfactants
    • become less hydrophilic with heat (CLOUD POINT)
• FREEZING & THAWING
  
  • ​induces aggregation / caking
    
    • ​due to pressure generated by crystal formations
• Temperature cycling
  
  • can cause Particle Growth
  • warming –> dissolve
  • Chilling –> precipitation
• ​SMALL PARTICLES GET SMALLER AND BIG PARTICLES GET BIGGER
  
  • ​= THERMODYNAMICS