Insensitivity of compaction properties of brittle granules to size enlargement by roller compaction

Sy Juen Wu, Changquan Sun

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64 Scopus citations


Pharmaceutical granules prepared by roller compaction often exhibit significant loss of tabletability, that is, reduction in tensile strength, when compared to virgin powder. This may be attributed to granule size enlargement for highly plastic materials, for example, microcrystalline cellulose. The sensitivity of powder compaction properties on granule size variations impacts the robustness of the dry granulation process. We hypothesize that such sensitivity of compaction properties on granule size is minimum for brittle materials because extensive fracture of brittle granules during compaction minimizes differences in initial granule size. We tested the hypothesis using three common brittle excipients. Results show that the fine (44-106 μm), medium (106-250 μm), and coarse (250-500 μm) granules exhibit essentially identical tabletability below a certain critical compaction pressure, 100, 140, and 100 MPa for spray-dried lactose monohydrate, anhydrous dibasic calcium phosphate, and mannitol, respectively. Above respective critical pressure, tabletability lines diverge with smaller granules exhibiting slightly higher tablet tensile strength at identical compaction conditions. Overall, tabletability of brittle granules is insensitive to granule size enlargement. The results provide a scientific basis to the common practice of incorporating brittle filler to a typical tablet formulation processed by roller compaction granulation.

Original languageEnglish (US)
Pages (from-to)1445-1450
Number of pages6
JournalJournal of Pharmaceutical Sciences
Issue number5
StatePublished - May 2007


  • Anhydrous dibasic calcium phosphate
  • Excipients
  • Granulation
  • Granule size enlargement
  • Lactose monohydrate
  • Mannitol
  • Roller compaction
  • Tabletability


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