Investigation of the effects of particle size on fragmentation during tableting

Particle size is a critical parameter during tablet production as it can impact tabletability, flowability, and dissolution rate of the final product.

The purpose of this study was to investigate the effect of initial particle size on fragmentation of pharmaceutical materials during tableting. Initial particle size fractions ranging from 0-125 to 355–500 µm of dibasic calcium phosphate (DCP), lactose monohydrate, and agglomerated and non-agglomerated microcrystalline cellulose (MCC) were blended with magnesium stearate and compressed into tablets. Larger initial particle sizes were found to fragment more extensively than smaller initial particle sizes for all materials based on the particle size distributions determined by laser diffraction.

DCP was found to fragment most extensively followed by lactose and both MCCs. The fragmentation degrees of DCP, lactose, agglomerated and non-agglomerated MCC reached 95, 81, 32, and 29%, respectively. These findings were further supported by an increase in specific surface area with increasing compression pressure of compressed particles. The NIR spectral baseline offset from tablets was found to increase with increasing compression pressure up to 50 MPa for all materials, which was the same compression pressure range where fragmentation was observed.

The NIR spectral slope from tablets as a function of compression pressure furthermore showed a similar trend as the tabletability profiles. NIR spectroscopy can thereby potentially be used as a surrogate control strategy for assessing compression related particle size changes and possibly tablet density and deformation behavior during tablet production. More on particle size effects in tableting