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Dry Blending - Problems and Remedies

Particle Agglomeration

Cause
Occurs with fine cohesive powders, which cause “balling up” and poor distribution

Remedy
  • Fine-screen cohesive compound into the bulk mix.
  • Use a more effective mixer (one with increased shearing action)
  • Blend the cohesive powder with a portion (5% to 10%) of an excipient; screen (mill) if necessary; reblend and add to the bulk; blend normally.
Note: For direct compression, excipient blends do not use a screen size or a mixer, which will change the excipient particle size distribution.


Nonuniformity of Mix

Cause: Remedy
  • Improper blender load: Use recommended powder load in a blender.
  • Insufficient mixing: Increase mixing time
  • Inefficient (improper) mixer: Use an alternative mixer with increased shearing action
  • Wide particle size distribution: Select more uniform particle sizes of components.
  • Over blending: Reduce blending time, Establish optimum mixing conditions
  • Low-dosage actives: Use a more effective mixer (one with increased shearing action).
  • Low-level excipients:
  1. Blend the low-level component with a portion (5% to 10%) of an excipient; screen (mill) if necessary; reblend; add to an equal quantity of excipient and mix; screen or mill if necessary; blend normally with the remainder of the bulk
  2. Dissolve the drug in a suitable solvent and add or spray onto a portion of the bulk or an excipient; blend; remove the solvent.
Note: For direct compression, excipient blends do not use a screen size or a mixer, which will change the excipient particle size distribution

Segregation after Blending

Cause: Remedy
Particle size distribution too wide: Use a narrower particle size range of components.

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