Quality by Design in the Processing of Oral Solid Dosage Forms: A Review

Quality by Design (QbD) is a systematic, science- and risk-based approach to pharmaceutical development that builds quality into the product and its manufacturing process instead of relying solely on end-product testing. This review discusses the application of QbD principles to the processing of oral solid dosage forms, mainly tablets. It describes the Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs), and examines how material properties and unit operations (blending, granulation, drying, milling, lubrication, compression and coating) influence tablet performance. Quality risk management, Design of Experiments (Plackett–Burman, Central Composite, Box–Behnken and mixed-level designs) and design-space development are presented as vital tools. The roles of Process Analytical Technology (PAT), near-infrared and Raman spectroscopy, real-time release testing and continuous manufacturing are also discussed. QbD demands considerable investment, multidisciplinary expertise, reliable data and suitable infrastructure, but offers a robust framework for uniform product quality, manufacturing efficiency and regulatory compliance throughout the product lifecycle. Artificial intelligence and machine learning may further improve prediction modelling, process optimisation and real-time quality monitoring.