Flowability characterisation of drug-excipient blends using a novel powder avalanching method

The scope of the work is twofold, first to introduce a new avalanche testing instrument and secondly to characterise flowability of pharmaceutical blends comprising of coarse and fine particles. The results were compared with established powder characterisation instruments like the angular shear cell and a flow through orifice tester. These different methods were applied to a broad concentration range of binary mixtures comprising coarse, well-flowing lactose and micronised, poorly flowing albendazole. Some of the mixtures were further analysed with scanning electron microscopy. The results showed clear changes in the flow behaviour of the mixtures that were considered as critical flow concentrations (CFCs). At least three drug concentrations were observed for which the flow behaviour essentially changed. Accordingly, different flow regions were identified, which were explained on the basis of changed particle packing configurations. A theoretical model successfully provided a first estimation of the initial two CFCs. In conclusion, the novel avalanche testing instrument provided complementary information to conventional flowability methodologies, and a thorough assessment of pharmaceutical blends is needed to avoid CFCs in view of a robust formulation development and hence with respect to building quality into the design of the solid dosage forms. (C) 2009 Elsevier B.V. All rights reserved.