The aim of this study was to investigate the granulation of piroxicam by fluidized bed hot melt method using polyethylene glycol 4000 as the hydrophilic carrier and spray dried lactose as the fluidizing substrate. The effects of the spray nozzle air flow rate, axial position of the spray nozzle and load of fluidizing substrate on granules properties were investigated using a Box Behnken factorial design. The dependent variables evaluated were the mean particle size distribution, drug content and flow properties of the granules. The granule sizes ranged from 453.5 mu m to 894.7 mu m and piroxicam content was above 83.2%. However, the response surface ANOVA showed that sizes and piroxicam content were not affected by the granulation conditions and microscopy evidenced the presence of piroxicam crystals on granules surface. On the other hand, ANOVA showed that the granules flow properties were affected at the significance level of 5%. Thermal and infrared analysis showed that there was no interaction of piroxicam with carriers during the process. The dissolution profile of piroxicam was remarkably improved. Therefore, the results confirm the high potential of the fluidized bed hot melt granulation technique to obtain granules with enhanced drug solubility and release rates. (C) 2018 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.