Impact milling of pharmaceutical agglomerates in the wet and dry states

This study focused on the milling of wet granulated agglomerates at points before and after drying in a typical high-shear pharmaceutical process train. These steps, referred to here as wet and dry milling, utilized a conical screen mill. Milling of granulation in the wet state eliminated 1–10 mm size agglomerates without affecting granule porosity or inducing further agglomeration. These millimeter-size agglomerates broke down during wet milling into moderately sized fragments larger than 125 μm. In contrast, when milled after drying, these same 1–10 mm-size agglomerates broke down predominantly into fine particles less than 125 μm. Data from screen-less milling trials suggest that the mill screen served only as a classifier and did not significantly contribute to the route of breakage for either wet or dry milling. However, in the case of dry milling, mill screens with grated surface textures did result in fewer fines than non-grated screens. This may be a result of reduced residence time in the mill. Experiments varying the size fraction of feed material and the rotational speed of the mill's impeller identified impact attrition as the primary mechanism governing dry granule breakage. The findings in this study shed light into the fundamental breakdown behavior of pharmaceutical agglomerates and demonstrate how breakdown of wet agglomerates via a de-lumping step prior to drying can lead to a reduced level of fine particle generation during dry milling.