SIZE REDUCTION (MILLING) —NOTES
1. INTRODUCTION
• Solid dosage forms (tablets, capsules) are the most common in pharmaceutics (>80%).
• Uniform particle size is required for:
o Accurate dosing
o Better dissolution
o Improved flow properties
• Raw materials are usually irregular and agglomerated.
→ Therefore, size reduction is essential.
• It led to the study of:
o Powder behavior
o Fracture mechanics
o Agglomeration
2. IMPORTANCE IN PHARMACEUTICAL INDUSTRY
• Used in:
o Tablet manufacturing
o Capsule filling
o Mixing and blending
o Drying processes
• Improves:
o Drug absorption
o Uniformity of dosage forms
• Even with direct compression, milling is still critical
3. APPLICATIONS OF SIZE REDUCTION
A. Wet Granulation Stage
• Produces uniform wet particles
• Improves drying efficiency (larger surface area)
• Prevents:
o Moist centers
o Over-dried particles
• Reduces:
o Drying time
o Fine particle formation
B. Dry Sizing Stage
• Ensures uniform particle size distribution (PSD)
• Improves:
o Flowability
o Bulk density
• Controls:
o Drug dissolution
o Drug release
• Increases surface area → better absorption
4. MECHANISM OF SIZE REDUCTION
A. Forces Involved
• Compression → crushing
• Impact → sudden force
• Shear → cutting
• Tension → pulling apart
👉 Usually a combination of forces acts together
B. Process Steps
1. Material exposed to stress
2. Energy stored as strain energy
3. When stress exceeds limit → fracture occurs
C. Weak Points of Particles
• Binder–particle interface
• Binder bridges
• Internal cracks
D. Wet Granules
• Break due to:
o Surface tension
o Capillary forces
5. ENERGY CONSIDERATIONS
• Only a small portion of energy is used for size reduction
• Most energy is lost as:
o Heat
o Noise
o Friction
o Vibration
6. MILLING TECHNOLOGIES
A. Hammer Mill
Working:
• Rotating hammers break particles by impact
• Particles pass through screen after size reduction
Advantages:
• Simple design
• Suitable for coarse grinding
Disadvantages:
• Not suitable for wet materials
• Produces excessive fines
• Blowback may occur
• Efficiency depends on feed direction
B. Oscillating Granulator
Working:
• Oscillating bars press material through mesh
• Uses low shear force
Advantages:
• Suitable for heat-sensitive and waxy materials
• Controlled particle size
Disadvantages:
• Low capacity
• High maintenance
• Risk of metal contamination
C. Conical Screen Mill (MOST IMPORTANT)
Working:
• Material enters chamber
• Impeller creates vortex
• Particles forced against screen → broken → discharged
Advantages:
• Low noise
• Low dust
• Uniform particle size distribution
• High capacity
• Low energy consumption
• No metal-to-metal contact
• Suitable for wet and dry materials
Types of Cone Mill
• Overdriven → feed from top
• Underdriven → feed from bottom
👉 Underdriven design:
• More efficient
• Smaller footprint
• Better integration
7. CRITICAL PARAMETERS IN CONE MILL
1. Impeller–Screen Gap
• Small gap:
o Faster discharge
o Less heat
o Fewer fines
• Large gap:
o More friction
o More retention time
2. Impeller Type
• Round bar → high compression (dry granules)
• Square bar → low shear (universal use)
3. Screen Type
Screen Type Application
Round hole Dry materials
Square hole Wet granules
Rectangular Elastic materials
Grater (rasp) Brittle materials
👉 Rule: Select hole size 2 steps larger than desired particle size
4. Tip Velocity
• Important for scale-up
• Must be maintained from:
o Lab → Pilot → Production
5. Feed Condition
• Best: Flood (plug) feeding
• Some materials require controlled feeding
8. MILL SELECTION CRITERIA
Consider:
• Particle size and shape
• Moisture content
• Temperature sensitivity
• Chemical properties
Also consider:
• Scalability
• Batch vs continuous process
• Safety (dust, explosion)
• Cleaning and maintenance
• Energy consumption
9. COMPARISON: CONE MILL vs HAMMER MILL
Feature Cone Mill Hammer Mill
Noise Low High
Dust Low High
PSD Uniform Wide
Wet & Dry Yes No
Feature Cone Mill Hammer Mill
Efficiency High Lower
👉 Cone mill is preferred in pharmaceutical industry
10. INERT MILLING
• Used for explosive/combustible materials
• Nitrogen gas is used
• Prevents:
o Fire
o Explosion
11. MICRONIZATION (FINE MILLING)
• Particle size: 1–30 µm
• Goal: uniform and narrow PSD
Methods:
• Pin mill
• Jet mill
• Fine grind mill
Fine Grind Mill
• Produces particles: 5–150 µm
• Advantages:
o Low heat
o Low dust
o Uniform distribution
Jet Mill (Fluid Energy Mill)
Working:
• Uses compressed air
• Particles collide → break
Features:
• No moving parts
• High efficiency
• Produces very fine particles
12. CRYOGENIC MILLING
Purpose
• Prevent heat damage
• Improve grinding of soft materials
Used For
• Waxes
• Rubber
• Heat-sensitive drugs
Cryogens Used
• Liquid nitrogen (most common)
• Carbon dioxide
• Dry ice
Liquid Nitrogen
• Temperature: -196°C
• Provides rapid cooling
• Safe with proper ventilation
Advantages of Cryogenic Milling
• Prevents:
o Melting
o Degradation
o Color change
• Makes materials brittle → easy grinding
13. KEY EXAM POINTS (REVISION) ⭐
• 4 forces: Compression, Impact, Shear, Tension
• Cone mill = most important in pharma
• Tip velocity critical for scale-up
• Micronization = 1–30 µm
• Cryogenic milling used for heat-sensitive materials