Methods: Effervescent granules containing citric acid and sodium bicarbonate were successfully prepared for the first time via TS-MG using a polyol (sorbitol) as a melt binder. Results: Processing parameters, specifically granulation temperature and screw speed, were systematically varied to investigate their influence. The granulation efficiency, inversely related to the wt.% of fines, decreased in the following order across the tested conditions (granulation temperature–screw speed; ℃-rpm): 95-6 > 100-5 > 90-5 > 100-7 > 90-7. Granulation temperature had a minimal impact on the bulk and tapped densities of the uncalibrated granules, whereas increased screw speed led to higher densities, associated with a reduced proportion of fines. The tensile strength of the resulting effervescent tablets increased with granulation temperature and was generally higher for tablets derived from granules with higher granulation efficiency. The residence time within the TS-MG barrel decreased with increasing temperature and screw speed. Notably, the greatest effect of granulation temperature on tensile strength occurred between 90 and 95 °C, particularly under longer residence times. The disintegration time of the tablets was shortest for the 90 °C and 5 rpm condition, corresponding to the lowest tensile strength, while tablets across formulations showed consistent homogeneity as indicated by similar pH values post-disintegration. Conclusions: These findings underscore sorbitol’s suitability as a melt binder and highlight the interplay between TS-MG parameters and the physical characteristics of effervescent granules and tablets.

Background: Polyols are widely used as tablet diluents due to their high solubility, favourable taste, and ability to form robust tablets. Thus, commercially available polyols, such as mannitol and isomalt, can be considered for the preparation of low-drug-dose formulations with a high polyol load. Methods/Results: This study investigated spray-dried mannitol (Mannogem^® XL Opal SD and Pearlitol^® 200 SD) and fluid-bed granulated isomalt (galenIQ™ 720 and galenIQ™ 721) at magnesium stearate levels of 0.5 and 3.0 wt.% and consolidation pressures of 100 and 300 MPa. During the tableting of 100 consecutive tablets, materials displayed different ejection force profiles: galenIQ™ 720 and galenIQ™ 721 demonstrated low and stable ejection pressures; Mannogem^® displayed a lubricant- and compaction pressure-dependent profile, whereas Pearlitol^® produced the highest ejection forces, particularly at 0.5 wt.% magnesium stearate. To elucidate these differences, the used materials were characterised in terms of SEM imaging, moisture content, surface area and porosity analysis, particle size distribution, pXRD, and densification kinetics. Using a compaction simulator, key parameters including pressure–displacement profiles, mean yield pressure, and strain rate sensitivity of the unlubricated materials were experimentally determined, while pressure transmission, residual die-wall pressure, and friction coefficient were computed. Conclusions: The study concluded that variations in tableting properties were primarily governed by moisture content and, for mannitol grades, by manufacturing method-dependent differences in particle microstructure. These insights provide guidance for the rational selection of polyol excipients and appropriate lubrication levels in direct compression tablet formulations.