Fluidized bed binderless granulation of hydrophobic drugs with fine lactose powder

To examine the applicability of pressure swing granulation (PSG), a fluidized bed binderless granulation method, to the production of pharmaceutical granules, the effects of drug particle size and concentration on the properties of PSG granules were investigated. The hydrophobic model drug powder and the model excipient powder used in this work were jet-milled 2-ethoxybenzamide (ethenzamide) powder and jet-milled lactose powder, respectively. Spherical granules of 355–1410 μm diameter were obtained with a high yield. The strength of product granules increased with increasing ethenzamide concentration when fine ethenzamide particles (dp,50 = 4:0 μm) were mixed with fine lactose (dp,50 = 3:8 μm). However, when coarse ethenzamide particles (dp,50 = 7:1 μm) were mixed with fine lactose powder (dp,50 = 3:1 μm), the tensile strength remained relatively constant regardless of the drug concentration. The product granules were sufficiently strong to maintain their shape during storage and sufficiently weak to disintegrate under a small compaction force. The drug contents in the product PSG granules were in good agreement with the predetermined values showing the good content uniformity of PSG products.