Format

Send to

Choose Destination
AAPS PharmSciTech. 2017 Aug;18(6):2368-2377. doi: 10.1208/s12249-017-0719-z. Epub 2017 Jan 26.

DEM Modelling of Granule Rearrangement and Fracture Behaviours During a Closed-Die Compaction.

Author information

1
Pharmaceutical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 3-16-89, Kashima, Yodogawa-ku, Osaka, 532-8505, Japan. furukawa.ryouichi@me.mt-pharma.co.jp.
2
Department of Chemical Engineering and Materials Science, Doshisha University, 1-3, Tatara Miyakodani, Kyotanabe, Kyoto, 610-0321, Japan. furukawa.ryouichi@me.mt-pharma.co.jp.
3
Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka, 569-1094, Japan.
4
Pharmaceutical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 3-16-89, Kashima, Yodogawa-ku, Osaka, 532-8505, Japan.
5
Department of Chemical Engineering and Materials Science, Doshisha University, 1-3, Tatara Miyakodani, Kyotanabe, Kyoto, 610-0321, Japan.
6
Department of Chemical Engineering and Materials Science, Doshisha University, 1-3, Tatara Miyakodani, Kyotanabe, Kyoto, 610-0321, Japan. yshiraka@mail.doshisha.ac.jp.

Abstract

The closed-die compaction behaviour of D-mannitol granules has been simulated by the discrete element method (DEM) to investigate the granule rearrangement and fracture behaviour during compaction which affects the compactibility of the tablet. The D-mannitol granules produced in a fluidized bed were modelled as agglomerates of primary particles connected by linear spring bonds. The validity of the model granule used in the DEM simulation was demonstrated by comparing to the experimental results of a uniaxial compression test. During uniaxial compression, the numerical results of the force-displacement curve corresponded reasonably well to the experimental data. The closed-die compaction of the modelled granules was carried out to investigate the rearrangement and fracture behaviours of the granule at different upper platen velocities. The forces during closed-die compaction calculated by DEM fluctuated in the low-pressure region due to the rearrangement of granules. A Heckel analysis showed that the force fluctuation occurred at the initial bending region of the Heckel plot, which represents the granule rearrangement and fracture. Furthermore, the upper platen velocity affected the trend of compaction forces, which can lead to compaction failure due to capping. These results could contribute to designing the appropriate granules during closed-die compaction.

KEYWORDS:

DEM; closed-die compaction; fracture; granule; rearrangement

PMID:
28127720
DOI:
10.1208/s12249-017-0719-z
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center