Reduction of Punch-Sticking Propensity of Celecoxib by Spherical Crystallization via Polymer Assisted Quasi-Emulsion Solvent Diffusion

Hongbo Chen, Shubhajit Paul, Hongyun Xu, Kunlin Wang, Mahesh K. Mahanthappa, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Punch-sticking during tablet compression is a common problem for many active pharmaceutical ingredients (APIs), which renders tablet formulation development challenging. Herein, we demonstrate that the punch-sticking propensity of a highly sticky API, celecoxib (CEL), can be effectively reduced by spherical crystallization enabled by a polymer assisted quasi-emulsion solvent diffusion (QESD) process. Among three commonly used pharmaceutical polymers, poly(vinylpyrrolidone) (PVP), hydroxypropyl cellulose (HPC), and hydroxypropyl methylcellulose (HPMC), HPMC was the most effective in stabilizing the transient emulsion during QESD and retarding the coalescence of emulsion droplets and the initiation of CEL crystallization. These observations may arise from stronger intermolecular interactions between HPMC and CEL, consistent with solution 1H NMR analyses. SEM and X-ray photoelectron spectroscopy confirmed the presence of a thin layer of HPMC on the surfaces of spherical particles. Thus, the sticking propensity was significantly reduced because the HPMC coating prevents direct contact between CEL and the punch tip during tablet compression.

Original languageEnglish (US)
Pages (from-to)1387-1396
Number of pages10
JournalMolecular pharmaceutics
Issue number4
StatePublished - Apr 6 2020

Bibliographical note

Funding Information:
H.C. thanks the Chinese Scholarship Council for partial financial support. H.C. also acknowledges partial support by a David Grant and Marilyn Grant Fellowship in Physical Pharmacy (2019–2020), Department of Pharmaceutics, University of Minnesota. H.X. and M.K.M. gratefully acknowledge the National Science Foundation DMR-1708874. XPS analyses were performed in the College of Science and Engineering Characterization Facility at the University of Minnesota, which also receives partial support from the National Science Foundation through the UMN MRSEC (DMR-1420013).

Publisher Copyright:
Copyright © 2020 American Chemical Society.


  • Celecoxib
  • HPMC
  • punch sticking
  • spherical crystallization
  • surface coating

How much support was provided by MRSEC?

  • Shared

PubMed: MeSH publication types

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


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