Opposing Effects of Additives in Dry Milling and Tableting of Organic Particles

Applying additives and excipients during the dry processing of fine particles is a common measure to control the particle–particle interactions, to specifically influence the powder properties and to enhance the process efficiency or product quality. In this study, the impacts of a particulate lubricant, a nano-disperse flow additive and liquid grinding aids on the dry fine milling and subsequent tableting of the ground material were investigated for three different organic model compounds. It is presented that the three additive classes cause varying and partly opposing effects during these process steps.

Especially the lubricant and the grinding aids were shown to increase the efficiency of the milling process as well as the product fineness of the ground material, and to avoid critical product adhesions on the machine surfaces. Thereby, stable and efficient grinding conditions were partially not possible without the addition of such additives. However, as these positive effects are attributed to a reduction of the adhesive forces between the particles, much lower tablet strengths were achieved for these additives. This propagation of powder, and in turn, final product properties over whole process chains, has not been studied in detail so far. It was further revealed that the material behavior and the microstructure of the product particles is decisive for the processing as well, which is why additive effects may be product-specific and can even be suppressed under certain processing conditions.

In comparison to the process performances, the powder properties and surface energies of the product particles were less influenced by the additives. On the contrary, particle-based morphologies or deformation behavior seem to play a major role in comparison to inorganic materials. Thus, it can be stated that global bulk properties and surface energies provide first indications of powder behavior and susceptibility. However, additional specific properties need to be evaluated to more clearly understand the influences of additives.

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Materials: In this study, two pharmaceutical excipients, α-lactose-monohydrate (CapsuLac60, Meggle, Wasserburg am Inn, Germany) and microcrystalline cellulose (Parmcel 102, Gustav Parmentier, Frankfurt am Main, Germany), as well as the model active pharmaceutical ingredient (API) theophylline, anhydrous (Acros Organics, Geel, Belgium), were used for the grinding and tableting experiments. Furthermore, two liquid and two particulate chemicals from different substance classes were used as additives (see Table 2). While the liquid additives are established as grinding aids for processing inorganic materials, the particulate additives are typically applied as flow aids (nanoscale silicon dioxide) or lubricants (sodium stearyl fumarate). In these experiments, the concentrations were chosen between 1 and 5 wt.% for the particulate and at 0.1 wt.% for the liquid additives respectively, related to the total powder mass. These concentrations correspond to typical additive amounts for processing particles in the lower micron scale.

Article information: Miethke, L.; Prziwara, P.; Finke, J.H.; Breitung-Faes, S. Opposing Effects of Additives in Dry Milling and Tableting of Organic Particles. Pharmaceutics 202113, 1434. https://doi.org/10.3390/pharmaceutics13091434

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