The impact of compaction by pellet type, spatial arrangement and drug release on MUPS tablets.

OBJECTIVES: This study aims to investigate the effect of compaction pressure, coating polymer, pellet core, and spatial arrangement on drug release behaviour in multiple-unit pellet system (MUPS) tableting. METHODS: Drug cores were produced by extrusion-spheronization or by drug layering onto sugar and microcrystalline cellulose (MCC) nonpareils, then coated with a sustained-release layer of acrylic (AC) or ethyl cellulose (EC). With MCC as the cushioning filler, coated pellets were manually arranged in separated or conjoint configurations and compacted into MUPS tablets at three compaction pressures using a compaction simulator. Dissolution testing was performed to evaluate drug release behaviour. KEY FINDINGS: Higher compaction pressure or use of a brittle coating polymer (EC) resulted in faster release. Pellets in direct contact were more prone to coat damage due to direct stress transmission, while separated pellets benefited from being completely encrusted by the cushioning filler, which aided in mitigating coat damage. Different pellet cores exhibited differing drug release behaviours, owing to their inherent properties. CONCLUSION: When producing sustained-release MUPS tablets, pellet core, coating polymer, and spatial arrangement, influenced by the pellet-to-filler ratio, need to be considered to achieve the desired drug release profiles and ensure robust dosage form performance after compaction.