Influence of the Porosity of Cushioning Excipients on the Compaction of Coated Multi-Particulates

The compaction of multiple unit-pellet system (MUPS) tablets poses considerable challenges due to potential compaction-induced damage to the functional polymer coat and segregation of pellets from other excipients during the tableting process. This study was designed to investigate the impact of porous pellets as cushioning agent without issues related to segregation while tableting.

Different drying techniques were applied to produce microcrystalline cellulose (MCC) pellets with various porosities. Sodium chloride was also added to the pellet formulation as a pore forming agent to generate a porous skeleton after production and aqueous extraction. The pellets fabricated were characterized for their porosity, crushing strength and yield pressure. Tablets were prepared using unlubricated pellets and their tensile strengths determined. Blends containing polymer-coated pellets and cushioning pellets of various porosities were compacted at different compaction pressures.

The porous pellets exhibiting the best cushioning effect were used for MUPS tableting at different compression speeds with both gravity and force feeders. The findings from this study showed that pellet porosity was highest when drying was carried out in a freeze dryer, followed by fluid bed and least porous from the oven. There was an inverse relationship between pellet porosity and strength. The protective effect of cushioning pellets was mainly dependent on their porosity. The porosity of pellets manufactured by leaching NaCl from MCC-NaCl (1:1) pellets were 2.14-, 2.57- and 4.88-fold higher than that of MCC PH101 only pellets for oven, fluid bed and freeze dried pellets, respectively.

Although the porosity of MCC PH101-NaCl (1:3) pellets was highest, they exhibited less cushioning effect than MCC PH101-NaCl (1:1). It was inferred that a good balance between porosity and bulk density of cushioning pellets was essential to be effective at protecting the coated pellets from damage during compaction. Compared with MUPS tablets prepared using unprocessed MCC PH105, the tablets prepared with the porous freeze dried MCC PH101 (NaCl fraction leached) pellets had improved drug content uniformity and were mechanically stronger.

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Author links open overlay panelRamy N.Elsergany, Lai Wah Chan, Paul Wan Sia Heng
European Journal of Pharmaceutics and Biopharmaceutics
https://doi.org/10.1016/j.ejpb.2020.05.015

Keywords: Porosity, Crushing strength, Cushioning effect, Sodium chloride, Freeze drying, Segregation, Uniformity