A holistic multi evidence approach to study the fragmentation behaviour of crystalline Mannitol

Jasdip S Koner, Ali Rajabi-Siahboomi, James Bowen, Yvonne Perrie, Daniel Kirby, Afzal R Mohammed

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
41 Downloads (Pure)


Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. However its fundamental disadvantage is its fragmentation during direct compression, producing mechanically weak tablets. The primary aim of this study was to assess the fracture behaviour of crystalline mannitol in relation to the energy input during direct compression, utilising ball milling as the method of energy input, whilst assessing tablet characteristics of post-milled powders. Results indicated that crystalline mannitol fractured at the hydrophilic (011) plane, as observed through SEM, alongside a reduction in dispersive surface energy. Disintegration times of post-milled tablets were reduced due to the exposure of the hydrophilic plane, whilst more robust tablets were produced. This was shown through higher tablet hardness and increased plastic deformation profiles of the post-milled powders, as observed with a lower yield pressure through an out-of-die Heckel analysis. Evaluation of crystal state using x-ray diffraction/differential scanning calorimetry showed that mannitol predominantly retained the β-polymorph; however x-ray diffraction provided a novel method to calculate energy input into the powders during ball milling. It can be concluded that particle size reduction is a pragmatic strategy to overcome the current limitation of mannitol fragmentation and provide improvements in tablet properties.

Original languageEnglish
Pages (from-to)16352
JournalScientific Reports
Publication statusPublished - 10 Nov 2015


  • chemistry
  • physical chemistry
  • thermodynamics


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