On the Fracture of Pharmaceutical Needle-Shaped Crystals during Pressure Filtration: Case Studies and Mechanistic Understanding

Pharmaceutical compounds often crystallise as particles with high aspect ratio, typically as needle-shaped particles. These particles must be isolated from the crystallisation liquors before further secondary processing to form the drug product. A common isolation method in the fine chemical and pharmaceutical industries is pressure filtration. Previous experience has shown that, on scale-up from lab to pilot plant, the particle size distribution can change quite significantly. This has typically been associated with agitation of the filter cake. To test this assumption a number of industrial case studies were conducted. The particle size distribution of various needle-shaped particles of different pharmaceutical and model compounds have been tracked through the filtration and drying process. The work here shows that, for the needle-shaped particles tested, particle breakage occurs during both pressure filtration and agitated drying. This is a previously unreported observation and is contrary to the previously held assumption that breakage is only observed during agitated drying. A mechanistic understanding of the breakage has been built up using particle dimensions, applied pressure, and bed density. The estimated stresses on the needle-shaped particles are of the same order of magnitude as typical tensile strengths of pharmaceutical materials, thus explaining why breakage is observed. A small-scale test has been developed to help identify potentially fragile compounds where breakage during pressure filtration is likely.