The influence of input material properties on hot melt granules prepared using a counter-rotating batch mixer

Afstathios Pafiakis, Piero Armenante, Costas G. Gogos

Research output: Contribution to journalArticlepeer-review


Objective: The objective of this study was to develop a method that enabled granulation in a counter-rotating batch mixer to emulate large scale dry twin screw granulation trials. Methods: Four granulations were prepared using counter rotating batch mixing for formulations containing a mixture of different particle sizes of the API (70% w/w) and polymer (30% w/w). Milled theophylline (MTHF; fine API) was blended with coarse hydroxypropyl cellulose (HPC MF; coarse polymer), theophylline (THF; coarse API) with fine hydroxypropyl cellulose (HPC EXF, fine polymer), and the other two formulations consisted of both components in the blend being fine or coarse. Results: The formulations selected for granulation had the lowest friction coefficient, f, as a function of drug load determined by the iShear® powder flow rheometer. Despite the non-uniform chaotic and random nature of thermal granulation, each formulation granulated reproducibly, though the evolution for each was different. Conclusion: This work highlighted that, firstly it is possible to measure plastic and frictional energy dissipation as product temperature. Secondly, granule growth and density were found to be proportional to the onset of polymer molecular mobility activated by the heat liberated from interparticle velocity differences via mechanical work (torque) required to move agglomerates through the mixer for the duration of each run.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalPharmaceutical Development and Technology
Issue number1
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Hot melt granulation
  • Twin screw granulation
  • agglomeration
  • frictional energy dissipation
  • plastic energy dissipation
  • sintering
  • viscous energy dissipation


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