Effect of Hydroxypropyl Cellulose Level on Twin-Screw Melt Granulation of Acetaminophen

Tongzhou Liu, Shubhajit Paul, Brian T. Beeson, Johnny Alexander, Fengyuan Yang, Vivian Bi, Thomas Durig, Changquan Calvin Sun, Feng Zhang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


This study investigated the effect of binder level on the physicochemical changes and tabletability of acetaminophen (APAP)-hydroxypropyl cellulose (HPC) granulated using twin-screw melt granulation. Even at 5% HPC level, the tablet tensile strength achieved up to 3.5 MPa. A minimum of 10% HPC was required for the process robustness. However, 20% HPC led to tabletability loss, attributable to the high mechanical strength of APAP granules. The over-granulated APAP granules had thick connected HPC scaffold and low porosity. Consequently, these granules were so strong that they underwent a lower degree of fracture under compression and higher elastic recovery during decompression. HPC was enriched on the surface of APAP extrudates at all HPC levels. Amorphous APAP was also observed on the extrudate surface at 20% HPC level, and it recrystallized within 24 h storage. To achieve a robust process and optimal improvement in APAP tabletability, the preferred HPC level was 10 to 15%.

Original languageEnglish (US)
Article number240
JournalAAPS PharmSciTech
Issue number7
StatePublished - Oct 1 2020

Bibliographical note

Funding Information:
This work is supported by PhRMA Foundation Research Starter Grant Pharmaceutics 2019.

Publisher Copyright:
© 2020, American Association of Pharmaceutical Scientists.


  • Binder content
  • Granule mechanical properties
  • Granule structure
  • Over-granulation
  • Twin-screw melt granulation


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