particle-size-reduction

Why is particle size important in pharmaceutical manufacturing?

• It affects material handling (e.g. flowability) and biopharmaceutical properties such as dissolution and bioavailability.

How does comminution (particle size reduction) affect drug dissolution and bioavailability?

It increases surface area, leading to a higher dissolution rate and potentially increased bioavailability if absorption is dissolution-limited.

Why is particle size critical for inhaled and transported pharmaceuticals?

It determines lung deposition site for inhaled drugs and increases bulk density, improving transport efficiency.

noyes whitney requation

• Dissolution rate ∝ surface area of the drug

• Increased by smaller particle size

• Increased by higher diffusion coefficient

• Increased by greater concentration gradient

what is milling?

• A mechanical process used to reduce particle size of solid materials

• Achieved by impact, compression, attrition, or shear forces

• Increases surface area, improving dissolution rate

• Improves flowability and uniform mixing in manufacturing

What is a cutter mill and how does it work?

• Uses rotating and stationary knives to cut particles

• Produces coarse particle size reduction

• Screen retains particles until the desired size is achieved

What is a hammer mill and how does it work?

• Hammers radiate from a central rotating shaft

• Particles are struck at high velocity

• Causes brittle fracture of most materials

What is a runner mill and how does it operate? edg and end

• Based on pestle and mortar (manual or mechanised)

• Edge runner mill: grinding occurs at the edge of a rotating wheel

• End runner mill: grinding occurs under the flat base of the rotating wheel

What is a roller mill and how does it work?

• Uses two rotating rollers (or one rotating, one stationary)

• Particles are crushed as they pass through the roller gap

• Speed difference between rollers introduces shearing action

What is a ball mill and how does it reduce particle size?

A:

• Hollow rotating drum partially filled (≈30–50%) with mill balls

• Rotation speed and feed volume are critical

• Balls are lifted by centrifugal force

• Avalanche (cascading) effect causes impact and attrition, reducing particle size

What is a vibration mill and how does it work?

• Mill chamber is ~80% filled with milling balls

• Vibration causes frequent impacts between balls and particles

• Produces fine particle size reduction

What is a pin mill and how does it reduce particle size?

• Consists of two discs with closely positioned pins

• Size reduction occurs by impact when particles collide with pins

• Also by attrition/shear between opposing pins

What is a fluid energy mill and how does it reduce particle size?

• Uses high-velocity air injected into a toroidal milling chamber

• Particles are suspended in turbulent airflow

• Size reduction occurs by particle–particle and particle–wall collisions

What is Griffith’s theory of brittle fracture?

• Materials contain microscopic cracks (flaws)

• During comminution, applied energy concentrates at crack tips

• When energy exceeds bond strength, the crack ruptures and propagates

How do cracks propagate according to Griffith’s theory, and how do tough materials differ?

• Cracks spread through weak regions with many flaws

• Elastic energy redistributes, concentrating at other cracks

• Causes a cascade effect → rapid brittle fracture

• Tough materials show ductile fracture with slower crack growth

What is deformation and how does it affect fracture?

• Deformation dissipates applied energy that might otherwise cause fracture

• Energy used in deformation is not available for crack propagation

• Therefore, deformation can reduce brittle fracture

What is the difference between elastic and plastic deformation?

• Elastic deformation: reversible; material returns to original shape when stress is removed

• All materials show some elastic deformation

• Plastic deformation: irreversible; permanent shape change

What is hardness and how is it measured?

• Hardness is the ability of a material to resist plastic deformation

• Measured in N m⁻² or using the Mohs’ scale (ordinal)

• On the Mohs’ scale: Diamond = 10, stainless steel ≈ 5

• Measured using hardness testers (e.g. Brinell, Vickers)

ow does hardness affect comminution?

• Hard materials are more difficult to comminute

• Require more energy for size reduction

• Can cause wear of milling equipment parts