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Particle Size Reduction in Pharmaceutical Industry

Particle-size reduction is a process of reducing particle size of substance in small size. Importance of size reduction include:

  • Enhance the mixing
  • Enhance the flow
  • Improve the bioavailability

Milling Concept

Few materials used in pharmaceuticals exist in the optimum size, and most must be comminuted at some stage or the other during the production of a dosage form.

Milling is the mechanical process of reducing the particle size of solids. Various terms (comminution, crushing, disintegration, dispersion, grinding, and pulverization) have been used synonymously with milling depending on the product, equipment, and the process.

Milled particles is classified as coarse, intermediate and fine according to the size of the particles. Size is conventionally expressed in terms of mesh (number of opening per inch square).
  • Coarse for particles size larger than 20-mesh
  • Intermediate (20-200) mesh (74 -840 micron)
  • Fine for particles size smaller than 200-mesh

Pharmaceutical Application

The surface area per unit weight, which is known as the specific surface, is increased by size reduction. In general, a 10-fold increase in surface area has been given by a 10-fold decrease in particle size. This increased surface area affects:

  • Dissolution and therapeutic efficacy: Dissolution and therapeutic efficiency of medicinal compounds that possess low solubility in body fluids are increased due to increase in the area of contact between the solid and the dissolving fluid.
  • Drying: The drying of wet masses may be facilitated by milling, which increases the surface area and reduces the distance that the moisture must travel within the particle to reach the outer surface.
  • Flowability: The flow property of powders and granules is affected by particle size and size distribution. The freely flowing powders and granules in high-speed filling equipment and tablet presses produce a uniform product.
  • Mixing or blending: The mixing or blending of several solid ingredients of a pharmaceutical is easier and more uniform if the ingredients are of approximately the same size. 
  • Formulation: 
    • Lubricants used in compressed tablets and capsules function by virtue of their ability to coat the surface of the granulation or powder.
    • A fine particle size is essential if the lubricant is needed to function properly.
    • The milling of ointments, creams, and pastes provides a smooth texture and better appearance in addition to improved physical stability.
    • Also, the sedimentation rate of suspensions and emulsions is a function of particle size and is reduced by milling.

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