Wet Granulation (Massing) - Problems and Remedies

Doughy Mass

Causes: Remedies
  • Too much water (often seen on scaleup): Add granulating water slowly; mix well after each addition.
  • Overmixing during granulation step: Reduce water or mixing time.
  • Wrong binder: Change Binder
  • Component of the mix (e.g., active drug or excipient): If possible, use alcohol/water or alcohol as granulating fluid - select appropriate binder; use Avicel PH-101, which gives 1. less sticky or doughy mass which is easier to screen, and 2. allows a wider range of solvent volume.

Moisture Sensitive Drugs

Causes: Remedies
  • Instability with water: 
  1. If possible, use ethyl alcohol or isopropyl alcohol (if latter, determine acceptable residual solvent by GC or another appropriate method) as granulating fluids, methylcellulose, and PVP as binders.
  2. Try slugging or roller compaction as dry granulation methods

Post a Comment