Scale-Up Strategy in Quality by Design Approach for Pharmaceutical Blending Process with Discrete Element Method Simulation.

摘要: An approach combining quality by design (QbD) and the discrete element method (DEM) is proposed to establish an effective scale-up strategy for blending process of amlodipine formulation prepared direct compression method. Critical parameters (CPPs) intermediate critical attributes (IQAs) were identified using risk assessment (RA) in QbD approach. A Box–Behnken was applied obtain operating space a laboratory-scale. DEM model developed input formulation; simulated on laboratory-scale V-blender (3 L) at optimal settings. The efficacy reliability validated through comparison simulation experimental results. Change evaluated when scaled-up pilot-scale (10 L). Pilot-scale double-cone blender settings derived from space. Both results suggest that time should be lower than optimized meet target values. These confirm change during process. Therefore, this study suggests QbD-integrated can desirable strategy.