Toward a Molecular Understanding of the Impact of Crystal Size and Shape on Punch Sticking

Shubhajit Paul, Lisa J. Taylor, Brendan Murphy, Joseph F. Krzyzaniak, Neil Dawson, Matthew P. Mullarney, Paul Meenan, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Punch sticking during tablet manufacturing is a common problem facing the pharmaceutical industry. Using several model compounds, effects of crystal size and shape of active pharmaceutical ingredients (API) on punch sticking propensity were systematically investigated in this work to provide molecular insights into the punch-sticking phenomenon. In contrast to the common belief that smaller API particles aggravate punch sticking, results show that particle size reduction can either reduce or enhance API punch sticking, depending on the complex interplay among the particle surface area, plasticity, cohesive strength, and specific surface functional groups. Therefore, other factors, such as crystal mechanical properties, surface chemistry of crystal facets exposed to the punch face, and choice of excipients in a formulation, should be considered for a more reliable prediction of the initiation and progression of punch sticking. The exposure of strong electronegative groups to the punch face facilitates the onset of sticking, while higher plasticity and cohesive strength aggravate sticking.

Original languageEnglish (US)
JournalACS Applied Materials and Interfaces
StatePublished - Apr 6 2020

Bibliographical note

Funding Information:
This work was supported by a grant from Pfizer Inc., U.S.A. Parts of this work were carried out in the Characterization Facility, University of Minnesota, a member of the NSF-funded Materials Research Facilities Network ( ) via the MRSEC program (no. DMR-1420013). We thank the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing the resources that contributed to the research results reported within this paper. URL: .

Publisher Copyright:
Copyright © 2020 American Chemical Society.


  • mechanical property
  • morphology
  • particle size
  • punch sticking
  • surface chemistry

How much support was provided by MRSEC?

  • Shared

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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  • MRFN

    Lodge, T.


    Project: Research project

  • University of Minnesota MRSEC (DMR-1420013)

    Lodge, T.


    Project: Research project

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