Investigation into the impact of sub-populations of agglomerates on the particle size distribution and flow properties of conventional microcrystalline cellulose grades

Abstract

Microcrystalline cellulose (MCC) is regarded as one of the most versatile tablet filler binders, finding a wide use in both granulation and direct compression operations. It has been shown that MCC particle populations consist of a mixture of ‘rod like’ primary particles, and agglomerates, and that the proportion of these primary particles and agglomerates differs within the different grades of materials, contributing to the different bulk properties of these materials. However, the proportion of primary particles and agglomerates has not previously been fully elucidated, and their contribution to the performance factors such as flow explained. In this paper we use a novel microscopy-based characterization technique to demonstrate that the proportion of ‘agglomerates’ in the series of MCC grades between PH101 and PH200 is, by number, very low, but sufficient to perturb a volume-based particle size method by significant amounts.

Keywords::

• Primary particle size
• agglomerates
• excipients
• flow

Acknowledgements

The authors would like to thank FMC Corp. for the donation of the batches of microcrystalline cellulose used for this study. The authors would also like to thank Dr Deborah Huck (Malvern), Dr Peter Timmins, Dr Michael Leane, Ms Helen Toale, Mr Jason Dawes, and Ms Vivienne Gray (all Bristol-Myers Squibb) for their support during this study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.