Inline Focused Beam Reflectance Measurement During Wet Granulation

Abstract Inline focused beam reflectance measurement (FBRM) is a valuable real-time monitoring process analytical technology (PAT) for granule size distribution. Chord length distribution (CLD) reported by FBRM inline inside a high-shear granulator (HSG) can differentiate particle size distributions (PSDs) within the ranges relevant to pharmaceutical processing. The CLD changes during processing is indicative of the progression of granulation, reproducibly delineates the effects of water amount, binder concentration, and impeller tip speed on the progress and outcome of wet granulation and correlates well with offline PSD measured by nested sieve analyses. The FBRM data can be tracked using an end-point indication algorithm, which assesses the process time needed to reach the target CLD and be useful for process monitoring and scaleup. This chapter highlights key studies that establish the capability of FBRM as a HSWG PAT exemplifying case studies of granulations whose end point is determined predominantly by granule growth (a placebo) or reduction of fines (an active formulation).