A series of tests were carried out in 10L and 60L PharmaConnect® granulators (GEA Process Engineering, Inc.). Two formulations were used. A placebo formulation consisted of microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, and different concentrations (1%, 3%, and 5% w/w) of HPC. 40% w/w water was added. A brivanib formulation consisted of brivanib alaninate, HPC, croscarmellose sodium and microcrystalline. 48% w/w, 58% w/w and 67% w/w water was added. Both formulations were pre-mixed for 30s and then water was added over the period of 3 minutes, followed by 20-25 min wet mass mixing. In all granulators the impeller tip speed was kept constant at 4.8 m/s.
DFF sensors (model P-4000-40) were used for the tests. The sensor was vertically inserted into the granulator bowl through an existing port in the lid and positioned inside the moving powder mass. The tip of the DFF sensor probe was positioned 2.54 cm above the blade at approximately half of the blade length from the center, at 90◦angle to the blade rotation. The second probe was inserted through the side port 3.3 cm and 5.9 cm above the blades for 10L and 60L granulators, respectively. LOI optical interrogator was used to record sensors response at 500 Samples/s rate.