Influence of compression at elevated temperature on the compactibility of thermo-mechanically processed polymers

Hot-melt extrusion (HME) is increasingly applied in the pharmaceutical industry for the formulation of solid dispersions of drugs with improved solubility and release. However, tableting of milled extrudates may present problems due to adverse thermo-mechanical effects on elasto-plasticity.

In this work compression of hot-melt extruded polyvinyl based and polymethacrylate polymers with glass transition temperatures (Tg) up to 80 °C was performed at ambient (20 °C) and elevated (40 °C, ‘hot’ compression) temperature aiming for compactibility improvement. Polymers were characterized for morphology, particulate properties, thermal properties, microhardness and compaction behavior (‘in-die’ force-displacement data). Hot-melt extruded polymers showed lower Tg and work of compaction but higher elastic recovery and yield pressure (Kuenz-Leuenberger and Kawakita models) resulting in weak tablets. ‘In all cases, ‘hot’ compression decreased considerably the yield pressure for both unprocessed and extruded polymers indicating greater plasticity.

For Eudragit® RSPO, Eudragit® L100-55 and Soluplus® with microhardness between 2.20 and 2.69 MPa it also increased consolidation due to softening of edges, thus facilitating interparticle slippage, which explained their tablet strength enhancement. Conversely, it did not affect the consolidation of Kollidon® SR with lower microhardness 0.31 and the large strength increase was attributed to the yield pressure reduction and the closeness of its Tg (42 °C) with the compression temperature increasing molecular mobility and operation of intermolecular forces.

Compared to ambient compression, greater plastic deformation due to ‘hot’ compression was visible in the SEM images of tablet surfaces by the extensive formation of interparticle boundaries and by the elimination of pores. Relationships were found between yield pressure, elastic recovery, tensile strength and friability of tablets with homologous compression temperature which may be useful during formulation. More on Influence of compression at elevated temperature on the compactibility of thermo-mechanically processed polymers