Preformulation - powder flow Flashcards
What is the importance of powder flow?
- 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
What are the mechanisms that govern powder flow?
Driving forces - Gravity and mechanical agitation
Resistive forces - cohesion/Adhesion and friction
How to calculate gravitational force?
F = m * g
m = mass of the particle
g = particle acceleration
What are adhesion and cohesion the result of?
- Van der Waals forces
- Electrostatic interactions
- Mechanical interlocking
What is meant by mechanical agitation?
External forces to induce powder motion and affect its flow behaviour.
What is cohesion?
Attractive forces between two chemically similar surfaces e.g. particle and particle
What is adhesion?
Attractive forces between two chemically different surfaces e.g. particle and equipment
Describe Van der Waals forces.
- Induced dipole-induced dipole interactions
- Greater if particles are larger and closer together
Describe electrostatic forces.
Tribocharging - surface statistics develop due to friction
Opposite charges attract; like charges repel
Describe mechanical interlocking.
- Rough surface texture
- Sharp edges
- Angular shapes
Describe friction.
- Present at contact surfaces where at least one surface is in motion.
- Acts in opposite direction versus direction of movement, thus inhibiting particle movement
State the particle properties that affect powder flow.
Size
Shape
Density
Surface texture
Moisture content
How does size affect powder flow?
Flow reduced as particle size decreases, due to greater adhesion forces
How does shape affect powder flow?
Optimal flow is provided by spherical particles which have minimal inter particulate contact
How does density affect powder flow?
Influence gravity and surface forces.
Denser particles generally have better flow.
How does surface texture affect powder flow?
Surface roughness affects powder flow due to its influence on particle adhesion.
Smooth surfaces increases flow.
How does moisture content affect powder flow?
The higher the amount of moisture, greater the risk of
cohesion and adhesion.
What does a larger surface area mean?
- Greater surface free energy
- More bonding interactions
- More cohesive
- Greater resistive forces
- Poorer flowability
What is significant about particle shape?
- Spherical has the smallest surface area of any particle shape
- Is less likely to mechanically interlock with another particle
State the significance of spherical particle.
- Smaller specific surface area
- Lower surface free energy
- Fewer bonding interactions
- Less cohesive
- Smaller resistive forces
- Better flowability
What is bulk density?
Density of solid particles plus entrapped air when the powder is allowed to settle naturally under gravity.
Bulk density = mass / bulk volume
What is tapped density?
Density of solid particles with minimal amount of entrapped air, after
consolidation using a pharmacopoeial method.
Tapped density = mass / tapped volume
What is particle density (true density)?
- 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
What does moisture content provide?
- 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
What are the 4 commonly reported methods for testing powder flow?
- Flow rate
- Density ratios
- Angle of repose
- Shear cell
How do we calculate flow rate?
Amount of powder discharged / discharge duration
Describe two methods of measuring flow rate.
Method 1
* Measure amount of powder discharged over a fixed duration
Method 2
* Measure time taken to discharge a fixed amount of powder
What does density ratios involve?
- Measure degree of volume reduction upon powder consolidation
- Standardised set of parameters (number of taps, drop height, dimensions of graduated cylinder)
What does angle of repose involve?
- 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
