Preformulation - powder flow

Question 1

What is the importance of powder flow?

Answer 1

• Powders are “building blocks” for many solid dosage forms.
• Critical significance in operations such as blending, tablet compression,
  capsule filling, transportation and scale-up operations.
• Can affect manufacturing efficiency and can directly affect:
• dosage form weight
• drug dose uniformity

Question 2

What are the mechanisms that govern powder flow?

Answer 2

Driving forces - Gravity and mechanical agitation

Resistive forces - cohesion/Adhesion and friction

Question 3

How to calculate gravitational force?

Answer 3

F = m * g

m = mass of the particle
g = particle acceleration

Question 4

What are adhesion and cohesion the result of?

Answer 4

1. Van der Waals forces
2. Electrostatic interactions
3. Mechanical interlocking

Question 5

What is meant by mechanical agitation?

Answer 5

External forces to induce powder motion and affect its flow behaviour.

Question 6

What is cohesion?

Answer 6

Attractive forces between two chemically similar surfaces e.g. particle and particle

Question 7

What is adhesion?

Answer 7

Attractive forces between two chemically different surfaces e.g. particle and equipment

Question 8

Describe Van der Waals forces.

Answer 8

• Induced dipole-induced dipole interactions
• Greater if particles are larger and closer together

Question 9

Describe electrostatic forces.

Answer 9

Tribocharging - surface statistics develop due to friction
Opposite charges attract; like charges repel

Question 10

Describe mechanical interlocking.

Answer 10

• Rough surface texture
• Sharp edges
• Angular shapes

Question 11

Describe friction.

Answer 11

• Present at contact surfaces where at least one surface is in motion.
• Acts in opposite direction versus direction of movement, thus inhibiting particle movement

Question 12

State the particle properties that affect powder flow.

Answer 12

Size
Shape
Density
Surface texture
Moisture content

Question 13

How does size affect powder flow?

Answer 13

Flow reduced as particle size decreases, due to greater adhesion forces

Question 14

How does shape affect powder flow?

Answer 14

Optimal flow is provided by spherical particles which have minimal inter particulate contact

Question 15

How does density affect powder flow?

Answer 15

Influence gravity and surface forces.
Denser particles generally have better flow.

Question 16

How does surface texture affect powder flow?

Answer 16

Surface roughness affects powder flow due to its influence on particle adhesion.
Smooth surfaces increases flow.

Question 17

How does moisture content affect powder flow?

Answer 17

The higher the amount of moisture, greater the risk of
cohesion and adhesion.

Question 18

What does a larger surface area mean?

Answer 18

• Greater surface free energy
• More bonding interactions
• More cohesive
• Greater resistive forces
• Poorer flowability

Question 19

What is significant about particle shape?

Answer 19

• Spherical has the smallest surface area of any particle shape
• Is less likely to mechanically interlock with another particle

Question 20

State the significance of spherical particle.

Answer 20

• Smaller specific surface area
• Lower surface free energy
• Fewer bonding interactions
• Less cohesive
• Smaller resistive forces
• Better flowability

Question 21

What is bulk density?

Answer 21

Density of solid particles plus entrapped air when the powder is allowed to settle naturally under gravity.

Bulk density = mass / bulk volume

Question 22

What is tapped density?

Answer 22

Density of solid particles with minimal amount of entrapped air, after
consolidation using a pharmacopoeial method.

Tapped density = mass / tapped volume

Question 23

What is particle density (true density)?

Answer 23

• Density of solid particles only (discounting air)
• Assumes non-porous particles

Denser particle =
* Greater mass at same volume
* Greater gravitational force
* Lower specific surface area
* Smaller resistive forces
* Better flowability

Question 24

What does moisture content provide?

Answer 24

• Binder property makes particles stick to surfaces and each other
• Liquid bridges between particles
• Provide lubrication
• Dry particles more likely to experience friction and generate statics
• Moderate moisture content provides balance between lubrication and cohesion

Question 25

What are the 4 commonly reported methods for testing powder flow?

Answer 25

- Flow rate - Density ratios - Angle of repose - Shear cell

Question 26

How do we calculate flow rate?

Answer 26

Amount of powder discharged / discharge duration

Question 27

Describe two methods of measuring flow rate.

Answer 27

Method 1 * Measure amount of powder discharged over a fixed duration Method 2 * Measure time taken to discharge a fixed amount of powder

Question 28

What does density ratios involve?

Answer 28

* Measure degree of volume reduction upon powder consolidation * Standardised set of parameters (number of taps, drop height, dimensions of graduated cylinder)

Question 29

What does angle of repose involve?

Answer 29

* Angle between slope and horizontal (θ) * Steepness of slope represents equilibrium of driving and resistive forces * Cohesion causes particles to pile up (stop flowing), increasing θ * Gravity causes particle to roll down slope (flow), reducing θ * More cohesive powder produces greater θ, poorer flowability