Abstract
Background/Objectives: Amorphous solid drugs exhibit physical instability and a propensity for crystallization, which leads to reduced solubility and bioavailability. Hence, this study optimized scale manufacturing parameters for producing a physically stable amorphous solid form of nilotinib using neutralization precipitation. Methods: A systematic evaluation of the effects of the solute concentration and filtration rate on amorphous physical stability was conducted using the pair distribution function (PDF), principal component analysis (PCA), and reduced crystallization temperature (R(c)) values. Results: It showed concentration-dependent crystallization resistance, with optimal physical stability achieved at a solute concentration of 0.126 mol/L and a 124 mL/min filtration rate. Experiments carried out at a scale of 50 g confirmed the stability of the production process. Conclusions: These findings provide a validated framework for developing lab-scale amorphous drug products with improved shelf-life stability, assessed using indirect indicators (PDF, R(c)) and confirmed through accelerated stability tests.