Twin-Screw Melt Granulation with Mannitol: High-Drug-Loaded Immediate-Release Tablets of Caffeine

High drug-loaded immediate-release formulations can be produced using a solvent-free and continuous melt-granulation method with a twin-screw extruder. Known and widely used high-molecular-weight and hydrophobic melt-binders result in weak tablets and negatively influence the disintegration and dissolution of tablets. Thus, this work aimed to probe mannitol as a melt-binder at a concentration of 30 wt.% and to investigate the effect of twin-screw melt granulation processing temperature and screw speed on the preparation of high drug-loaded immediate-release caffeine tablets with superior mechanical properties. A two-level design of experiment with three center points was used for the screening of the effect of barrel temperature and screw speed on granules and tablets properties. Model drug caffeine was mixed with mannitol (Parteck® M100), while a Pharma 11 extruder with helix feed screw elements and without a nozzle was used for twin-screw melt granulation. Processing conditions were found to significantly influence the solid state of ingredients and the quality of granules. Mannitol, as a melt-binder at a concentration of 30 wt.% at given processing conditions, was proven as an efficient melt-binder for high drug-loaded immediate-release tablets with superior mechanical properties.