Milling Mechanisms in Pharmaceutical Processing

Particle Size Reduction

• Comminution, pulverization, milling, and grinding are synonyms for size reduction
• Size reduction aids in further processing by facilitating powder mixing and increasing the dissolution rate of soluble ingredients.
• For suspensions, size reduction reduces sedimentation rate.
• Size reduction reduces bulk material volume, aiding transport.

Applications of Size Reduction in Pharmaceutical Industry

• Dissolution and therapeutic efficacy: Increased surface area per unit weight enhances drug dissolution in body fluids.
• Extraction: Smaller particles allow more thorough extraction with less solvent penetration depth.
• Drying: Size reduction increases surface area and shortens the moisture travel distance, speeding up drying.
• Flowability: Free-flowing powders and granules enhance product quality in equipment like high-speed filling.
• Mixing: Similar particle size makes mixing of ingredients easier and more uniform.
• Formulation: Fine particle size is crucial for lubricants to properly coat granules or powders, ensuring smooth texture and stability in ointments, creams, and pastes.

Mechanisms of Size Reduction

• Different milling equipment types produce an approximate size reduction range.
• The extent of size reduction is related to milling time.
• Mills apply energy for size reduction through different mechanisms such as:
  • Cutting
  • Compression
  • Impact
  • Attrition

Mechanisms of Milling

• Cutting: Applying force over a narrow area using a sharp edge slices material into smaller pieces (example: knife mills for fibrous materials).
• Compression: Material crushing between surfaces under pressure (example: roller or jaw crushers for brittle materials).
• Impact: Material contact with a fast-moving part, transferring kinetic energy, leading to internal stress and particle breakage (example: hammer mills for brittle and soft materials).
• Attrition: Material subjected to shear forces from relative motion of surfaces, leading to particle breakage (example: fluid energy mills for fine grinding).

Equipment

• Cutter Mills: Use knives or cutters to reduce size for small and large-scale processes.
  • Rotary knife cutters well-suited for tough, fibrous materials.
  • Disc Mills suitable for pre-milled or suspended materials.
• Runner Mills (Mortar and Pestle): A mechanized form used for smaller-scale size reductions.
• Three-Roller Mill: Consist of multiple rollers of different speeds to crush and shear materials between rollers.
• Hammer Mills: Consist of hammers rotating rapidly to impact particles and fracture them. Used for sticky materials that clog other mills and for granulating damp masses.
• Vibration Mills: Cylindrical tanks filled with porcelain/steel balls that vibrate, creating impacts for size reduction.
• Ball Mills: Rotating cylinders with balls inside for impact and attrition size reduction.
• Fluid Energy Mills (Jet Mills or Micronizers): High-velocity fluids and high-pressure jets for size reduction and minimizing heat generation.
• Pin Mills (Kek Mills): Two discs with closely spaced pins, one rotating at speed for impact and attrition size reduction.

Factors Affecting Size Reduction

• Nature of the material: Material hardness, brittleness/plasticity, stickiness, and fibrous nature are influencing factors. Different materials require different techniques.
• Moisture Content: Dry powders (less than 5% water) are easily reduced - higher water levels or wet milling are required.
• Temperature: Heat generation can degrade heat-sensitive materials, melt materials with low melting points, or induce explosions in unstable compounds.
• Particle Shape: Size reduction methods may lead to irregular (tough) or regular/spherical (easy flow) particles.
• Product Specifications: Desired particle size, shape, moisture content, and physical/chemical properties.
• Sanitation Ease of cleaning, auxilary equipment compatability and operation mode are influencing factors.
• Economic considerations Equipment costs, power/labor and costs, and space requirements.
• Dust Control: Minimizing dust and reducing risks associated with contamination.

Applications

• Intermediate powders can come from almost any substance.
• Suitable for processing sticky materials, powdering barks, leaves, roots, filter cakes.
• Also used for granulating techniques.

Advantages

• Various materials.
• Controlled product size.
• Continuous operation.
• Little metal abrasion and little contamination.

Disadvantages

• Heat generation.
• Clogging during operation and machine damage.
• Wide size range of product.
• Increased wear of component materials.
• High energy consumption.

Wet vs. Dry Milling

• Dry milling (~100 µm) often involves higher power consumption and creates more dust, while wet milling (~10 µm, limited by flocculation) often eliminates dust and requires less power but may create a need for drying. Wet milling is favored when the product is moisture-sensitive.

Factors Affecting Size Reduction Choice

• Product specifications affect material properties and size reduction techniques.
• Equipment type and its processing capabilities affect production batch sizing, and materials handling.
• Sanitation, operational methods, dust control, and cost affect mill selection.