Assessment of impact breakage of carbamazepine dihydrate due to aerodynamic dispersion.

ABSTRACT

Acicular crystals are very common in pharmaceutical manufacturing. They are very prone to breakage, causing unwanted particle size degradation and problems such as segregation and lump formation. We investigate the breakage pattern of carbamazepine dihydrate, an acicular and platy crystal with cleavage planes. It readily undergoes attrition during isolation and drying stage, causing processing difficulties. We use the aerodynamic dispersion of a very small quantity of powder sample to induce breakage by applying a pulse of pressurised air. The dispersion unit of Morphologi G3 is used for this purpose. The broken particles settle in a chamber and are subsequently analysed using the built-in image analysis software. The shift in the particle size and shape distributions is quantified through which the extent of breakage is determined as a function of the dispersion pressure. The analysis reveals a change of breakage mechanism as the dispersion pressure is increased from primarily snapping along the crystal length to one in which chipping has also a notable contribution. The breakage data are analysed using a modified impact-based breakage model and the breakability index of the carbamazepine dihydrate is determined for the two breakage regimes. The method provides a quick and easy testing of particle breakability, a useful tool for assessing attrition in process plant and grindability in milling operations.