Polymorphic transformation of l-glutamic acid monitored using combined on-line video microscopy and X-ray diffraction

Enhancement of process monitoring for detecting transformations of the organic solid state is an important, strategic area currently of substantial interest particularly to the pharmaceutical sector and, more generally, manufacturers of speciality chemical products. A feasibility study is reported in which a solution-mediated polymorphic transformation of l-glutamic acid (LGA) was monitored using, concurrently, both video microscopy accompanied by advanced image processing and, on-line X-ray diffraction. The applicability of these monitoring approaches, applied individually, has been demonstrated previously; however, it was useful to assess the relative sensitivity of the two techniques by their direct comparison, via simultaneous use, during application on-line to monitor a polymorphic transformation process. It was found that the onset of the polymorphic transformation, manifested as the point in time when crystals of the β phase of LGA were first detected, was elucidated as being significantly sooner via video microscopy. This reflects the fact that the concentration regimes of maximum sensitivity for the individual approaches are complementary, hence video microscopy provides considerable added-value allowing detection of the early stages of the transformation process. Currently, the upper bound on solids concentration that is compatible with extracting useful information about the phase composition using video microscopy, based on particle shape, is restricted. However, it is anticipated that improvements to both the experimental design and the image processing algorithms applied will substantially increase this upper bound allowing practical application under realistic processing conditions.