Many orally administrated drugs exhibit poor bioavailability due to their limited solubility. The smartFilm technology is an innovative approach to improve the drug aqueous solubility, where the drug is embedded within the matrix of cellulose-based paper in an amorphous state, hence increasing its solubility. Despite its proven effectiveness, smartFilms, i.e., pieces of paper, exhibit limited flowability and are not easy to swallow, and thus oral administration is not convenient. In addition, there is a lack of knowledge of their mechanical behavior under compression. This study aimed to transform unloaded smartFilms, i.e., paper, into a flowable physical form and investigated its mechanical behavior when compressed. Granules made of paper were prepared via wet granulation and were compressed into tablets. The influence of using different amounts and forms of sucrose, as a binder, on the pharmaceutical properties of the produced granules and tablets was studied and the most suitable composition was identified by using instrumented die experiments. For this, the Poisson’s ratio and Young’s modulus were determined for different compaction force levels and the deformation behavior was estimated with the Heckel mathematical model. All granule batches showed good flowability with angle of repose values between 25–35°. Granule batches with ≤30% dry sucrose content produced tablets that fulfilled the European Pharmacopeia requirements, and the compaction behavior of the granules was found to be comparable to the behavior of classical binders and compression enhancers. Paper can be transferred into granules. These granules can be used as suitable intermediate products for the production of tablets made of paper in large, industrial scale.

Background: The compaction of formulation blends is a critical stage in pharmaceutical tablet manufacturing, particularly when drug substances or functional excipients exhibit limited flowability and tabletability. Objectives: This study systematically examined the mechanical behaviour of viscoelastic microcrystalline cellulose (MCC) and brittle anhydrous dibasic calcium phosphate (DCPA), as well as their mixtures, to check how deformation mechanisms influence powder handling and tablet performance. Methods: A compaction simulator, mimicking a small rotary tablet press, was used to evaluate tablet weight variability, densification profiles, die-filling height, force–displacement behaviour, and in-die Heckel analysis. Additional assessments included compression times, breaking force, tensile strength, elastic recovery, as well as in-die and out-of-die tablet thickness across various compositions and compaction pressures. Results/Conclusions: Bulk density values from the simulator showed strong correlation with pharmacopeial measurements (R² ≥ 0.997). Measurable differences in true density and cohesiveness led to poor flowability for MCC and good flow for DCPA, with mixtures containing higher DCPA concentration displaying markedly improved flow characteristic. Compaction analyses confirmed extensive plastic deformation for MCC and fragmentation for DCPA. Increasing MCC content elevated die-fill height, compaction energy, and tablet weight variability, whereas higher DCPA fractions decreased apparent density of tablets and reduced energy demand. Tabletability and compressibility profiles reflected that MCC generated hard tablets but exhibited higher elastic recovery, while DCPA formed softer tablets with closer to linear strength–pressure relationships. Energy profiling demonstrated that MCC stored more elastic energy and required higher overall compression work, whereas DCPA reduced elastic accumulation. Overall, blending viscoelastic and brittle excipients offers a robust strategy for optimizing manufacturability, mechanical strength, and energy efficiency in tablet production.

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.