Optimization of precipitation conditions for producing physically stable amorphous solids using pair distribution function and reduced crystallization temperature

Abstract

The physically unstable amorphous solid drug can transform into a crystalline state, reducing solubility and dissolution rate. This study aimed to prepare physical stability anticancer drug nilotinib free base amorphous solids by modifying parameters associated with amorphous precipitation, including washing water volume, drying time, and anti-solvent/solvent ratio. Characterization involved powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and data analysis involved pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA) were applied for the physical stability evaluation. The results revealed that amorphous solids showed the highest physical stability under specific conditions: 50 mL washing water volume, 18 h drying time, and 40 anti-solvent/solvent ratio. Hence, it was demonstrated that the method combining PDF analysis and Rc values provided a novel and comprehensive assessment of physical stability, offering enhanced speed and accuracy compared to traditional accelerated stability test approaches.