W2.1_Powder Flow

Question 1

What are the operations in drug manufacturing that includes powder transfer? Explain the impact of poor powder flow in drug compound. Define powder and flow.

Answer 1

• Solid dosage forms: most common in pharmaceutical manufacturing, with operations including powder transfer (ex. Mixing, granulation, dispensing)
• Poor powder flow -> X content uniformity, X tablet weight uniformity, capping/lamination -> out of specification -> harm patient safety and increase final cost
• Powders: particles with <1000µm, containing one or more components, mixture of particles and air (g/s colloids) (*powder flow can also be applied to granules, which are >1000µm)
• Flow: net movement of mass over time

Question 2

Describe the nature of powder flow. What are the thermodynamics of powders govenered by?

Answer 2

• Powder can be poured like liquids/compressed like gases/deformed like solids (∴ colloid)
• Thermodynamics of powders: not governed by kT (Avogadro constant and temperature)
• ∴ X affected by temperature -> use potential energy instead (governed by mgd)
• m: mass, d: diameter of particle, g: gravitational constant
• mgd is much larger than kT

Question 3

Describe the regular powder flow and state the shape of the container.

Answer 3

• *Assuming no other external forces
• Formation of v-shaped dent -> propagate downwards -> residue remaining
• (∴ hopper is used to prevent residues)

Question 4

Explain the different types of irregularities in powder flow (4).

Answer 4

• Segregation: mixture of heavy and light particles -> light ones flow first and faster
• Rat holing: too adhesive and cohesive
• Bridging: too cohesive
• Residue: too adhesive

Question 5

Explain the two opposite properties regarding molecular interactions. What are the forces involved (3)? Briefly explain the principle that allows powder flow to occur.

Answer 5

• Adhesion: between two chemically different surfaces (container & particles)/between particles in multicomponent mixture
• Cohesion: between two chemically similar surfaces (between particles)
  Forces involved:
• Van der Waals’ interactions: F(vdW)=A*R(s)/12a^2
  A: Hamaker constant a: separation distance between two particles Rs: radius of particle
• Electrostatic interactions (hydrogen bonds, ionic bonds)
• Capillary interactions: F(c)=2πRγ (≈sticky interactions of particles on water surface)
  γ: surface tension of liquid (usually water) R: radius of particle
• Requirement: ∑ƒ(driving forces) > ∑ƒ(drag forces)
• Driving forces: gravitational force, particle mass, mechanical forces
• Drag forces: adhesive forces, cohesive forces, other surface forces

Question 6

Explain how particle size impact powder flow and dissolution rate.

Answer 6

Smaller particle size -> higher surface area to volume ratio -> more van der Waals’ forces -> more cohesive -> poorer powder flow (but better dissolution rate)

Question 7

Explain how different particle shapes (3) can impact powder flow.

Answer 7

• Regular and spherical: small contact surface area -> less cohesion + less vdW’ forces -> optimum powder flow
• Irregular: cause preferred orientation with large SA contact -> poor powder flow
• Particle flakes: may cause interlocking, surface roughness causes short separation distance -> poor powder flow

Question 8

Explain how packing of molecules impact powder flow.

Answer 8

• Cubic packing has higher porosity than rhombohedral packing
• Smaller SA contact, weaker vdW’ forces
• Increased air flow can improve powder flow

Question 9

Regarding density, define bulk density, tapped density, Hausner ratio, % compressibility and Carr’s index. Relate the limit values to powder flow.

Answer 9

• Free flowing: bulk density ρ(B)=m/V(B)
• Consolidated: tapped density ρ(T)=m/V(T)
• Hausner ratio=ρ(T)/ρ(B) x 100 (If <1.18: good)
• % Compressibility=(ρ(T)-ρ(B))/ρ(T) x 100
• Carr’s index = 1-% Compressibility (If <15: good)

Question 10

Define angle of repose and its relationship to powder flow.

Answer 10

tan α = height/radius
If <35 degrees: good

Question 11

Explain critical arch diameter and the testing methods.

Answer 11

• Diameter of arch in bridging scenario
• Arch diameter = load/shear area x 4/bulk density
• Methods: Jenike shear tester, Ring shear tester

Question 12

Explain ways to improve powder flow (4).

Answer 12

• Increase particle size -> reduce adhesive and cohesive forces (by granulation/crystallisation)
• Alter shape/texture of particles (by crystallisation/spray drying)
• Add additives (flow activators/glidants): reduce adhesion and cohesion (ex. colloidal silicon dioxide reduces bulk density and improves flowability)
• Use of vibration-assisted hoppers/force feeders: provide mechanical force to prevent residue/bridging