Industrial Pharmacy II - Size Reduction

Industrial Pharmacy II - Size Reduction

• Definition: Size reduction is the process of reducing large solid particles to smaller particles using mechanical means.
• Objectives of Size Reduction:
  • Preparation of suspensions
  • Facilitating mixing of powders
  • Increasing surface area, thus increasing drug material solubility
  • Reducing bulk for easier shipping
  • Exposing cells for extraction purposes

Factors Affecting Size Reduction

• Hardness: A measure of a material's resistance to scratching. Harder materials are more difficult to reduce in size. Mohs Hardness Scale is used to measure mineral hardness.
• Toughness: The ability of a material to resist fracture or deformation under stress. More important than hardness when reducing size; soft and tough materials can present more problems than hard, brittle substances (e.g., blackboard chalk is easier to break compared to rubber). Moisture content affects toughness; green herbs are tougher than dry ones.
• Stickiness: Gummy or resinous materials (like myrrh) may adhere to grinding surfaces, or screen meshes become blocked. Complete dryness of the material or adding inert substances (e.g., kaolin) can help.
• Abrasiveness: Hard minerals can create abrasive effects during grinding, possibly contaminating the final powder with metal particles from the milling equipment (more than 0.1% reported).
• Temperature: Heat generated during grinding can soften substances like waxy materials (e.g., stearic acid) or materials containing oils, fats, gums, or resins. Use of water jackets or passing air through the equipment and using liquid nitrogen can help.
• Material structure: Some materials are homogenous in character; others may have weaknesses along lines or are composed of fibrous particles (e.g., vegetable drugs have a cellular structure).
• Moisture content: High moisture content affects hardness, toughness, and stickiness. Dry grinding requires less than 5% moisture, while wet grinding requires more than 50% moisture.
• Physiological effect: Some very potent substances (like hormones) can have dangerous effects from dust; enclosed mills and/or specialized air extraction systems, and wet grinding are suggested solutions.
• Purity required: Size reduction equipment can cause the grinding surface to wear, which can affect product purity and requires high levels of purity for certain products.
• Ratio of feed size to product size: Machines producing fine products typically require a smaller initial product size; and often a process with different equipment (e.g., preliminary crushing, followed by coarse grinding and fine grinding) is needed.

Size Reduction Methods

• Cutting: The material is cut using a sharp blade or multiple blades.
• Compression: The material is crushed by applying pressure.
• Impact: Material is hit by a high-speed object or particles. Stationary material is shattered into smaller pieces.
• Attrition: Material is subjected to pressure while surfaces move relative to each other; resulting in shear forces that break particles.
• Combined impact and attrition: Examples of comminuting methods; produce size reduction by both impact and attrition (e.g., ball mills, fluid energy mills, pin mills).

Size Reduction - Advantages in Pharmacy

• Increases surface area, which increases solubility and dissolution.
• Enhances bioavailability.
• Improves extraction rates.
• Improves mixing of materials, leading to proper weight.
• Improves color and active ingredient dispersion.
• Controls particle size distribution, minimizing segregation.
• Improves drying rates.

Size Reduction - Disadvantages in Pharmacy

• Change in polymorphic form of active ingredient (renders it less active or inactive).
• Drug degradation caused by heat buildup (during milling), oxidation, or adsorption of unwanted moisture.
• Decreased bulk density can affect material flowability.

Equipment for Size Reduction

• Structures for feeding material to the mill: First component
• Milling chambers and working parts: Second component - holds the mill.
• Receivers or collectors to deposit the milled product: Third component.
• Ball mill: Examples include simple, tube, Harding, rod, and vibration mills; can reduce size by both impact and attrition, used for batch and continuous operations. Advantages: capable of grinding wide varieties of materials with different hardness degrees, equal suitability for wet or dry grinding, control of dust and toxic hazards. Disadvantages: wear and tear, soft/sticky materials may cake, noisy, difficult/time-consuming cleaning and high energy requirements / cost.

Ball Mill Operation Speed

• Low speeds: Mass of balls slide/roll over each other, causing minimal size reduction.
• High speeds (above critical speed): Mill operates centrifugally; no grinding.
• Optimum speed (two-thirds critical speed): Grinding occurs by impact and attrition.