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Mixing in Pharmaceutical Engineering

Mixing is a unit operation that involves manipulation of a heterogeneous physical system with the intent to make it more homogeneous. Mixing can be achieved by the following processes:

  • Hand Mixing (Using Spatula)
  • Mortar & Pestle (Trituration)
  • Tumbling & Shaking (Diffusion)
  • Shear Mixing (Low Shear: Planetary Mixer, High Shear- Mixer-Granulator)
  • Fluid Bed Process

Objective of Mixing

  • To produce a homgenous physical mixture
  • To produce physical change
  • To produce dispersion
  • To promote chemical reaction

Type of Mixing

  • Diffusion Mixing : by Random movement (Using Blender or Bin)
  • Convection Mixing: Displacement of group of particles from one place to another (Auger Mixer, Ribbon Mixer) 
  • Shear Mixing: By effecting mechanical energy to change the configuration of ingredients (High Shear Intensive Mixer).

Danckwerts (Danckwerts, 1953) classified mixing as follows:

  • Positive mixing: spontaneously and completely mix.
  • Negative mixing: separation is occurred unless continuously agitated.
  • Neutral mixing: neither mixing nor demixing takes place unless any force is applied.

Mode of Mixing

1. Geometric Dilution: In Pharmaceuticals this is mostly used for making an intermediate concentrate pre-mix for actives, colors or any other ingredient in a very small amount in the product composition. 

2. Ordered Mixing: It is a non-randomized process. In this process materials are selectively mixed based on their physical characteristics (cohesive, adherence, ruggedness, irregular shape, coating, and/or flow properties) this process is widely used in the Pharma Industry and can be achieved in a number of ways.

3. Mechanical: By Dividing and Recombining, Mixing & Screening

  • Selective mixing of the low drug load <5% API with a carrier with irregular surface area (e.g. Anhydrous Lactose, Mannitol etc.). Thus the career excipient due to its rugged irregular surface attaches the low amount drug substance forming an API-carrier mixture concentrate for ultimate BU and CU of the drug product. 
  • Selective mixing of high drug load >50% API of non-cohesive property with a cohesive ingredient to induce compaction for a Direct Compression (D.C) Process.

Mixing Equipment

  • Diffusion Mixing: V-Blender, Slant-cone Mixer, Double-cone Mixer & Bin Blender
  • Convection Mixing: Auger Mixer & Ribbon Mixer
  • Shear Mixing: Low-shear Planetary Mixer, High-shear Intensive Mixer

Related: Blending in Pharmaceutical Manufacturing

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