Raman microspectroscopic mapping or thermal system used to investigate milling‐induced solid‐state conversion of famotidine polymorphs

Confocal Raman microspectroscopy was used to nondestructively determine the polymorphic conversion of famotidine in the course of the milling process. A mapping system was applied to assess the blending uniformity of each polymorphic component in the milled mixture. Raman microspectroscopy combined with a thermal analyzer was also used to investigate the synergistic co-effects of milling and heating on the polymorphic conversion of famotidine polymorphs. Famotidine has two polymorphs, forms A and B, the raw material of famotidine used was proved to be of form B. The Raman peak intensity ratio of the 2920 cm−1 band for form A and 2897 cm−1 band for form B was used to act as an indicator to evaluate the polymorphic conversion of famotidine form B to form A after different milling courses. The results indicate that the peak intensity at 2897 cm−1 gradually decreased with the milling time, whereas the peak intensity at 2920 cm−1 slowly enlarged, suggesting the polymorphic conversion of famotidine from form B to form A. The longer milling process might strongly induce and promote this polymorphic conversion of famotidine. Both polymorphic forms of famotidine were found to be well uniformly distributed within the milled samples due to their smaller varieties by using the Raman microscopic mapping system. The temperature effect could synergistically accelerate the polymorphic conversion of famotidine from form B to form A in the milled sample. The thermal-dependent critical temperature for sharply enhancing the content of famotidine form A in each milled sample was also identified. Copyright © 2007 John Wiley & Sons, Ltd.