Quality by design strategies in fluidized bed granulation: A focus on granules for tablet manufacturing

The study aimed to apply the Quality by Design (QbD) methodology to optimize the fluidized-bed granulation process to produce high-quality pharmaceutical granules intended for tablet manufacturing. Research focused on defining the Quality Target Product Profile (QTPP) and identifying Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs) crucial to ensuring product quality. The experimental design employed a three-level fractional factorial design to investigate the effects of key process parameters, including the mass flow rate of the binder, the temperature of the inlet air, and the drying time, on the granulation results. Measurements such as particle size distribution, moisture content, and flowability were used to assess the granules. The results indicated that parameters such as the inlet air temperature and drying time significantly impact the quality of the granules, confirming their status as CPPs. Further analysis of tablet mass and hardness revealed that these granule properties directly influenced tablet uniformity and mechanical strength.The application of the failure mode and effect analysis (FMEA) matrix helped to identify and prioritize these critical parameters based on their risk priority number (RPN). The study concluded that a systematic QbD approach, combined with a robust experimental design and risk management, is crucial for optimizing the fluidized-bed granulation process. This ensures consistent production of granules with the desired quality attributes and enhances the safety and efficacy of the final pharmaceutical product.