Real-Time Assessment of Granule Densification and Application to Scale-up

Abstract This chapter describes the use of a drag force flow (DFF) sensor to probe wet mass consistency in real time and its correlation to granule densification using two formulations. A placebo and a brivanib alaninate formulation were granulated with different concentrations of binder or water, respectively, while comparing DFF sensor response with granule size growth and densification assessed independently. The wet mass consistency parameter correlated well with granule densification, which is known as a critical material attribute that correlated with tablet dissolution. In addition, comparison of responses from focused beam reflectance measurement (FBRM) and DFF sensors are presented to assess complementarity of information on granulation progress from the two probes. The DFF sensor was able to quantitatively characterize with high resolution a response of wet mass consistency distinct from granule size distribution. Finally, application of DFF sensor to scaleup of granulation is demonstrated.