Quality by Design-Based Scale-Up and Industrial Development of Turmeric Extract-Loaded Nanostructured Lipid Carriers

Background/Objectives: A robust and scalable manufacturing framework for lipid-based nanocarriers remains a critical challenge, particularly for labile phytochemicals such as curcuminoids in turmeric. This study presents an integrated Quality by Design (QbD)-driven and Outcome-Based Design (ObD) strategy to establish a scalable, resource-efficient manufacturing process for curcuminoids-loaded nanostructured lipid carriers (NLCs). Methods: To overcome the limitations of conventional multivariate design of experiments (DOE), which require extensive experimental runs, a risk-based, knowledge-driven single-factor screening approach was employed. Guided by risk assessment tools, including Ishikawa diagrams and failure mode considerations, 12 representative processing conditions were selected to define the design space. Critical quality attributes (CQAs), namely, particle size, polydispersity index (PDI), and zeta potential, were predefined to establish a robust control strategy. A two-step homogenization process-high-shear homogenization (HSH) for pre-emulsification followed by high-pressure homogenization (HPH) for nanoscale refinement-was systematically optimized. Results: Multivariate data analysis using principal component analysis (PCA) and hierarchical cluster analysis (HCA) identified key critical process parameters (CPPs), particularly HSH speed, processing time, and HPH cycles, as dominant factors influencing nanoparticle characteristics. The optimized 1-h process enabled successful scale-up of NLCs from 100 g to 5000 g, demonstrating the capability to generate nanosized particles within 100-500 nm. The combined HSH-HPH approach produced smaller, more uniform nanoparticles with high encapsulation efficiency and physical stability, outperforming HSH alone. Conclusions: Overall, this study establishes a practical and industrially viable framework that integrates QbD principles with data-driven optimization tools, for enabling reliable translation from laboratories to semi-industrial production.