Powder bed packing and API content homogeneity of granules in single drop granule formation

Tianxiang Gao, Arun S.S. Singaravelu, Sarang Oka, Rohit Ramachandran, František Štepánek, Nikhilesh Chawla, Heather N. Emady

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Single drop granule formation on a static powder bed of pharmaceutical mixtures was studied to investigate the effects of hydrophobicity and primary particle size distribution on the powder bed packing structure and the content homogeneity of active pharmaceutical ingredient (API) in granules formed. The granule formation mechanisms, drop penetration time, granule morphology and internal structure have been previously investigated in a mixture of coarse microcrystalline cellulose (MCC) and fine acetaminophen (APAP). When the APAP amount increased (decreasing particle size and increasing hydrophobicity), drop penetration time increased, formation mechanisms transitioned from Spreading to Tunneling, the granules became smaller in size, and the internal porosity of the granules decreased (Gao et al., 2018). In the current study, single drop granulation on mixtures of MCC and APAP with different particle sizes were investigated for formation mechanisms and granule morphology. Additionally, the powder bed packing structure was characterized by X-ray micro-CT and the API content uniformity was measured by UV–vis spectrometry. It was found that in the mixture made from coarse MCC and fine APAP, the internal structure became heterogeneous and there were dense aggregate regions in both the powder bed and granules from 25% APAP proportion, where the transition from Spreading to Tunneling occurs. The content uniformities of granules from fine powder beds are much more compromised (indicating a discrepancy between the actual value and theoretical value) than those from coarse powder beds. This content discrepancy becomes much larger when the APAP proportion in the powder bed is higher (above 50%). This was previously observed by other researchers (Nguyen et al., 2010) and was attributed to the preferential wetting of the ingredients. It is believed that the primary particle size of the powder bed is more significant than the hydrophobicity in affecting the formation mechanism, granule internal structure, and content uniformity.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalPowder Technology
StatePublished - Apr 15 2020


  • Content uniformity
  • Granule formation mechanism
  • Powder packing structure
  • Single drop wet granulation

ASJC Scopus subject areas

  • General Chemical Engineering


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