A formulation strategy for solving the overgranulation problem in high shear wet granulation

Frederick Osei-Yeboah, Minglun Zhang, Yushi Feng, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Granules prepared by the high shear wet granulation (HSWG) process commonly exhibit the problem of overgranulation, a phenomenon characterized by a severe loss of the ability to form adequately strong tablet. We hypothesize that the incorporation of brittle excipients promotes brittle fracture of granules during compaction, thereby improving tablet mechanical strength by increasing bonding area. On this basis, we have examined the effectiveness of incorporating a brittle excipient into a plastic matrix in addressing the overgranulation problem. A complete loss of tabletability is observed for plastic microcrystalline cellulose (MCC) when ≥55% of granulating water was used. The incorporation of a brittle excipient, either lactose or dibasic calcium phosphate (Dical) into the MCC matrix leads to improved tabletability in a concentration-dependent manner, with higher amount of brittle excipient being more effective. For each mixture, tablet tensile strength goes through a minimum as the granulating water increases, for example, 1.4 MPa for the mixture containing 80% of lactose and 2.1 MPa for the mixture containing 80% Dical. These results, along with scanning electron microscope evidence, show that the addition of brittle excipients to an otherwise plastic powder is an effective formulation strategy to address the overgranulation problem in HSWG.

Original languageEnglish (US)
Pages (from-to)2434-2440
Number of pages7
JournalJournal of Pharmaceutical Sciences
Issue number8
StatePublished - Aug 2014


  • compaction
  • formulation
  • granulation
  • materials science
  • powder technology
  • tablet


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