Influence of Neutralization Precipitation Conditions on the Physical Stability of Amorphous Solid Pharmaceuticals

This research focused on the precipitation of amorphous forms of nilotinib with high physical stability through the manipulation of various parameters in the neutralization reaction, specifically the quantity of nilotinib, the pH value, and the concentration of HCl. To assess the physical stability of the amorphous nilotinib, various characterization techniques, including PXRD, DSC, and FBRM, were utilized in conjunction with analytical methods such as PDF, PCA, and R_c value. The findings demonstrated that the ideal physical stability was attained with a nilotinib quantity of 0.5 g, a pH value of 11.70, and 7.5 mL of HCl with a concentration of 2.0 mol/L. It is important to acknowledge that this observation is specific to the current experimental configuration and may not hold in the context of a scaled-up experiment. Furthermore, the combination of PDF and R_c was identified as an innovative and effective method for assessing physical stability, demonstrating advantages over traditional accelerated stability testing approaches.