Analysis of over-granulated particles using near-infrared chemical imaging and attenuated total reflectance-infrared techniques

Abstract

To elucidate the previously described mechanism of segregation caused by over-granulation, we analyzed over-granulated particles using the techniques of near-infrared chemical imaging (NIR-CI) and attenuated total reflectance infrared (ATR-IR). The same area of over-granulated particles was measured using both techniques. The distributions of the active ingredient, ethenzamide, and other additives in the over-granulated particles were compared. As ATR-IR chemical imaging easily identifies components and has higher spatial resolution than NIR-CI, it permitted a clearer observation of the distribution of ingredients, particularly in fine cornstarch particles. Using both techniques, segregation of components were observed as previously reported. Although lactose was barely observed in the ethenzamide-enriched regions, ethenzamide and cornstarch were observed in lactose-enriched regions. This suggests that only lactose aggregated and segregated from the other compounds during the process of granulation. Hydrophilic lactose aggregation is supposedly caused by the behavior of water during granulation. In conclusion, ATR-IR chemical imaging is an excellent analytical technique for obtaining the detailed distribution of components. Furthermore, fusion of ATR-IR chemical imaging and NIR-CI is a useful tool for understanding drug manufacturing processes and may be applicable to pharmaceutical manufacturing and quality control.