Quantification of Fragmentation of Pharmaceutical Materials After Tableting.

Deformation is the material property that is a key for successful tablet formulation. Still, a quantitative method for assessing the change in particle size as a result of compression is lacking. The purpose of this study is to introduce a method for quantifying fragmentation after tableting. Different size fractions of dibasic calcium phosphate, microcrystalline cellulose, lactose, and starch were blended with magnesium stearate and compressed into tablets. The compressed particles were recovered from the tablets by manual grinding, which was possible by the addition of magnesium stearate. The recovered particles were subjected to scanning electron microscopy and particle size distribution (PSD) analysis. Fragmentation was quantified by characterizing the change in PSD. PSDs of the compressed samples with increasing compression pressures were analyzed, and more specifically, the particle sizes from the inflection point were used to generate a fragmentation profile. The fragmentation profiles of dibasic calcium phosphate and lactose showed extensive fragmentation during tableting; microcrystalline cellulose fragmented slightly, whereas starch did not fragment at all. The results furthermore showed that the mechanical strength of the tablet was highly dependent on fragmentation, as the mechanical strength did not start to increase before almost all fragmentation had occurred. Hence, by using this method, it is possible to quantify at which compression pressure and to which degree materials fragment during the tableting process.