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Anomalous Particle Size Shift During Post-milling Storage

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Abstract

Purpose

To investigate the anomalous phenomenon of particle size shift during post-milling storage.

Materials and Methods

Crystallised and ball-milled adipic acid were stored under different humidity conditions. Analyses were carried out to characterise changes in particle size distribution (laser diffraction), morphology (SEM), bulk flow properties (annular shear tester), surface adhesion forces (AFM) and crystallinity (PXRD and DVS).

Results

It was observed that the particle size distribution of milled adipic acid can shift to finer fractions, remain unchanged, or even shift to coarser fractions depending on storage conditions. SEM analysis showed that milled adipic acid is composed of agglomerates, which can undergo de-aggregation or further agglomeration via re-crystallisation. Empirical analysis ruled out the effects of electrostatic charges on the particle size shift. In addition, an improvement in powder flow in terms of bulk tensile strength was seen for milled adipic acid stored under high relative humidity but not under low humidity.

Conclusions

Storage of milled adipic acid below the critical relative humidity led to localised disintegration from the agglomerate surface and particle size reduction, which was not influenced by moisture sorption or loss. This evidence supports that “stress relaxation” mechanism behind particle breakage of post-milled particles. Appropriate storage conditions are important in maintaining the stability of milled powders.

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Acknowledgements

The authors would like to thank Junwei, Chin Lee, Ron Lim, Ai Tee, Prashant, Lay Yong, Gary Liu and Wenyi for their contribution in particle characterisation and Aaron Yuen for assisting in theoretical calculations.

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Authors and Affiliations

  1. Crystallisation and Particle Sciences, Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore, 627833, Singapore

    Wai Kiong Ng, Jin Wang Kwek & Reginald B. H. Tan

  2. Department of Chemical and Biomolecular Engineering, The National University of Singapore, 4 Engineering Drive 4, Singapore, 117576, Singapore

    Reginald B. H. Tan

Authors
  1. Wai Kiong Ng
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  2. Jin Wang Kwek
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Correspondence to Wai Kiong Ng.

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Ng, W.K., Kwek, J.W. & Tan, R.B.H. Anomalous Particle Size Shift During Post-milling Storage. Pharm Res 25, 1175–1185 (2008). https://doi.org/10.1007/s11095-007-9497-8

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  • DOI: https://doi.org/10.1007/s11095-007-9497-8

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