In situ monitoring of wet granulation using online X-ray powder diffraction

Purpose. Polymorphic transformations during the wet granulation of a metastable polymorph of flufenamic acid were monitored in situ using online X-ray powder diffraction. The resulting data were used in testing a proposed process induced transformation rate model, which allows the extent and occurrence of polymorphic transformations during wet granulation to be controlled by adjusting the granulation time. Methods. A small-scale, top mixing granulator was designed for compatibility with novel X-ray powder diffraction equipment ( available from X-Ray Optical Systems of East Greenbush, NY). Results. The unique polycapillary optic and X-ray source allowed the transformation of the metastable to the stable polymorph to be followed during the granulation. Following a diffraction peak each for the metastable and stable forms demonstrated that polymorphic transformations during the wetting phase of granulation follow the trends predicted by the model. Conclusions. The advanced online monitoring may allow real-time control of the process by the adjustment of process parameters, such as granulation time, and clearly qualifies as a PAT ( process analytical technology).