Development Of Process Analytical Technology (PAT) Models For Real-Time Quality Assurance In Tablet Manufacturing

Abstract

The research aimed to develop and validate a micro-scale PAT framework for real-time monitoring of critical quality attributes during tablet manufacturing using minimal resources. Micro-batches (20g total) containing Ibuprofen (1.0g), Paracetamol (1.0g), lactose monohydrate (15.0g), microcrystalline cellulose (2.0g), croscarmellose sodium (0.8g), and magnesium Stearate (0.2g) were processed using mortar-pestle blending (5min), manual wet granulation, single-punch compression (10 tablets/batch), and brush-coating. Handheld NIR (blend uniformity/moisture) and Raman (coating thickness) spectrometers provided real-time monitoring. Chemo metric models (PCA/PLS) were developed using Python's Scikit-learn library. PAT implementation reduced blending time by 30% (5 vs 7min control) while improving content uniformity (RSD 2.1% vs 4.8%). Tablet hardness remained consistent (5.5±0.3 kg/cm²), and coating thickness variation decreased to RSD 3.2% (vs 8.7% control). Real-time moisture control prevented over wetting (8.5-9.5% w/w). Statistical analysis (paired t-test, p<0.05) confirmed significant quality improvements. The approach demonstrated PAT's effectiveness despite material limitations. This study successfully established a cost-effective PAT framework for academic labs, proving that real-time quality assurance is achievable with micro-batches and portable instrumentation while aligning with pharmaceutical quality principles.