ABSTRACT
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).
Subject(s)
Technology, Pharmaceutical/methods , Flufenamic Acid/analysis , Models, Chemical , Pharmaceutical Solutions , Powder Diffraction , Spectrophotometry, Ultraviolet , Technology, Pharmaceutical/instrumentation , X-Ray Diffraction/methodsABSTRACT
A data-collection method for macromolecular crystals using convergent sources is described here. Because of the unique characteristics of the diffraction patterns, a software package CBMPRO has been developed specifically for processing data images collected with the convergent beam method (CBM). The resulting data sets from crystals with two different sets of unit-cell parameters are presented and compared. There is good agreement between data sets from the same type of crystals under slightly different experimental conditions and data sets collected and processed with CBM also agree well with those from conventional oscillation methods, marking an important step to establishing CBM as a viable alternate data-collection method for macromolecular crystals.