Unraveling local heat generation in twin-screw melt granulation.

Granule growth in twin-screw melt granulation (TSMG) is driven by viscous and frictional heat dissipation at the kneading block. The formation of larger, stronger granules requires the screws to input more energy into processing the material, resulting in local heat generation (ΔTlocal), as indicated by difference between the peak granule temperature and the set barrel temperature. Understanding ΔTlocal is essential for comprehending TSMG and expanding its use in pharmaceutical manufacturing. This study examined the effects of process parameters and binder levels on ΔTlocal using paracetamol or acetaminophen (APAP) as model drug and KlucelFusionTM X HPC (hydroxypropyl cellulose) as binder. The Q/N ratio (feed rate to screw speed), representing degree of fill, and the staggering angle of the kneading block significantly impacted ΔTlocal. Specific mechanical energy (SME) showed a strong correlation with ΔTlocal, with higher SME resulting in greater ΔTlocal. These results highlighted the complex interaction between process parameters and binder levels, and their combined effect on SME and ΔTlocal. Materials were exposed to elevated temperatures (93 °C to 110 °C) for short duration (≤33 s). Higher SME and ΔTlocal led to increased particle size reduction of APAP post-granulation. Granule growth was achieved at a low binder level (5 % KlucelFusionTM X HPC), producing tablets with the desired tensile strength (> 2 MPa) and less drug's particle size reduction compared to a 10 % binder level. These findings underscore the benefits of using the 5 % binder in TSMG for effective granulation with minimal particle size reduction of the drug during granulation.