ROLL COMPACTION: IMPACT OF RAW MATERIALS COMPRESSION PROPERTIES ON THE QUALITY ATTRIBUTES OF RIBBONS AND GRANULES

Dry granulation in a roller compactor (RCDG) is a process widely used in the pharmaceutical industry that involves the compression of powders by two counter-rotating rollers to produce ribbons, which are milled to produce granules. This process is ideal for moisture-sensitive materials, as it requires no liquids, and is both fast and cost-effective. However, it can generate fine particles or cause excessive densification, reducing tabletability. Ribbon properties are influenced by process parameters and material properties (e.g., compaction behavior); in fact, not all materials are suitable for this process. Although different studies investigated the effect of process parameters on ribbons and granules, limited attention has been given to the role of raw material properties. As a consequence, this study aims to evaluate the influence of the compression behavior of the materials on the final ribbon properties. Four formulations were selected for this study, consisting of mixtures of Microcrystalline Cellulose (MCC), Monohydrate Lactose (LAC), and Anhydrous Calcium Hydrogen Phosphate (EMC). Specifically, MIX A contains 74.625% (w/w) LAC and 24.875% (w/w) MCC, MIX B contains 74.625% (w/w) MCC and 24.875% (w/w) LAC, MIX C contains 74.625% (w/w) EMC and 24.875% (w/w) MCC, and MIX D contains 74.875% (w/w) MCC and 24.875% (w/w) EMC. Additionally, 0.5% (w/w) Magnesium Stearate was added to all formulations as a lubricant. Raw materials and their mixtures were characterized for particle size distribution, flowability, moisture content, true density, and compaction behavior (Heckel and Kawakita parameters, Py and a ∗ b). MCC exhibited a plastic deformation mechanism, reflected in its low Py value, whereas LAC and EMC followed a fragmentation mechanism, indicated by high Py values. Mixtures generally reflected the dominant component’s properties. Powders were blended using a high shear mixer with a micro-NIR sensor to assess uniformity. Formulations were compacted using a lab-scale roll compactor (GFC-LAB Micro GRANUFORCE™) under varying forces and screw speeds. MIX C failed to produce ribbons due to its high EMC content, which inhibited strong interparticle bonding. Ribbons were analyzed for crushing strength, density, and morphology. Results showed that MIX B and MIX D required higher screw speeds for consistent ribbon formation due to MCC’s pronounced plasticity, and increasing sensitivity to process variations. In contrast, MIX A produced ribbons v within a narrow screw speed range but generated more fines, attributed to LAC’s fragmentation mechanism and excessive roller adhesion. However, all the ribbons are not homogeneous along the longitudinal direction and generally show greater strength in the center. This result is probably due to the geometry of the lab-scale instrument. Under the conditions studied, the screw speed is the most significant factor influencing the strength and density of the ribbons; an increase in the screw-to-roll speed ratio corresponds to an increase in ribbon strength and density. To produce consistent compacts, it is essential to use mixtures that demonstrate plastic behavior. The ribbons were then milled using a laboratory-scale knife mill to obtain granules with a diameter of less than 500 µm. Granules were characterized to evaluate their granule size distribution, density, and compression behavior. The results highlighted that although the ribbons are not homogeneous, the resulting granules are compressible and uniform. The granules obtained from MIX A exhibit a fragmentation behavior, while those from MIX B and MIX D display a more plastic behavior. Tablets were subsequently produced by compressing the granules, and their tensile strength was assessed. The results indicated that granules from MIX A required higher compression forces to produce stable tablets. Conversely, granules from MIX B and MIX D required lower compression forces and resulted in stronger tablets.