Polymorph Screening Using Near-Infrared Spectroscopy

Abstract

Near-infrared spectroscopy was utilized as a polymorph screening method. A model compound (sulfathiazole) was recrystallized from various solvents, and the crystals were milled using a planetary ball mill and compressed using a hydraulic press. The polymorphism of recrystallized and processed samples and the effect of processing on the polymorphism of sulfathiazole was studied by near-infrared (NIR) spectroscopy and verified by X-ray powder diffraction (XRPD) and thermal analysis. Polymorphism and the degree of crystallinity of the processed samples were studied, and NIR spectroscopy proved to be a fast tool for polymorph screening and monitoring the processing-induced transformations. After clustering of the NIR spectra of various samples, XRPD and complementary methods can be applied to a more thorough analysis of different clusters. This approach provides a timesaving improvement for the polymorph analysis in the case of large number of samples.

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

“…Aaltonen et al have monitored the decrease in crystallinity, when crystalline sulfathiazole samples were milled at room temperature. 44 However, in contrast to Shakhtshneider and Boldyrev, 41,42 they did not observe any polymorph transformations in the XRPD patterns of samples subjected to mechanical treatment.…”

“…44,46 Sulfathiazole form III and amorphous sulfathiazole show clear spectral differences in the 7000-6200 cm -1 and 5150-4850 cm -1 ranges (Fig. 3), which encompass the region where the first overtones for the N-H stretching vibrations and the combination bands of N-H stretching and NH2 bending vibrations are expected.…”

Solid-State Transformations of Sulfathiazole Polymorphs: The Effects of Milling and Humidity

“…However, apart from an increase in amorphous content, no transformations between sulfathiazole polymorphs by mechanical activation were observed in the X-ray powder diffraction (XRPD) analysis of the processed samples reported by Aaltonen et al [19]. However, since those studies examined the effect of milling on just one or two polymorphic forms in this work the extent of polymorphic transformations on all five sulfathiazole forms during milling neat and with solvent and excipients is examined.…”

A combined approach of differential scanning calorimetry and hot-stage microscopy with image analysis in the investigation of sulfathiazole polymorphism

“…At present, it has five known polymorphs that are well characterised and clearly described in the literature [24][25][26]. Although the polymorphism of sulfathiazole has been extensively and repeatedly investigated by various researchers [27][28][29][30], it remains difficult to produce a pure polymorph; most of the time, the desired polymorph contains impurities from at least one other form [31][32][33][34].…”