Process Analytical Technology (PAT) and QbD in Formulation Science

List of Practicals

1. Identify Critical Quality Attributes (CQAs) – Brainstorm and list five tablet (hardness, dissolution, etc.) and link each to patient safety or efficacy.
2. Ishikawa (Fish-Bone) Diagram – Draw a cause-and-effect diagram for poor dissolution, categorising factors into Materials, Methods, Machines Manpower.
3. Blend-Uniformity by NIR Probe – Collect in-line near-infrared spectra during min of blender operation and plot real-time API concentration trends.
4. Moisture Tracking with NIR – Use a portable NIR gun to measure LOD granules every 2 min, stopping when the plot hits the 3 % target.
5. Mini DoE for Granulation – Run a 2² design varying impeller speed and granulation time; measure granule mean size and create main-effects plots.
6. Real-Time Release Test (RTRT) – Set up an at-line NIR hardness prediction test 20 tablets, and compare predicted vs. actual hardness.
7. Control Chart of Particle Size (FBRM) – Stream Focused Beam Reflectance during milling; plot X̄ and R for d₅₀ and decide if the process is in control.
8. Multivariate Calibration Model – Build a partial-least-squares (PLS) correlating NIR spectra to drug content; report R² and RMSEP.
9. FMEA Risk-Priority Number – Score severity, occurrence and detectability three high-risk process variables; rank them by RPN and suggest mitigation.
10. PAT Model Verification Batch – Run the optimised process, capture PAT confirm that all CQAs meet specification without end-product testing.