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 come out from a rotating shaft 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?

Easier to enemroide 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 is the change in shape or size of a material when a force is applied to it.

Deformation absorbs energy, so less energy is left to grow cracks. This means deformation helps prevent 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