Dry granulation by roller compaction of paracetamol with different grades of mannitol

Roller compaction dry granulation is a manufacturing technology that has been increasingly used in the pharmaceutical industry for improving the flowability and bulk density of powder mixtures or to prevent segregation problems of high-potency drugs before tableting. To compare the potential of four different commercial grades of mannitol, powder (PO), spray-dried (XL and EZ) and granular (GR), in addressing the formulation of drugs with poor flowability and compaction properties, this work evaluated the performance of binary mixtures of these grades with varying contents (20–80%) of paracetamol powder, a material considered a model for having shown critical issues in this respect. Granules obtained with these mixtures by roller compaction at different pressures were characterized in terms of particle size distribution, bulk density, flow properties and tableting ability. Particles with the desired size (500–1300 μm), increased bulk density and appropriate flow properties could be achieved. Regarding tableting ability of granules, mixture prepared with mannitol spray-dried (XL and EZ) allowed to obtain the most resistant tablets at 20% drug content and an important reduction of tableting properties was observed at 40% and tableting with higher paracetamol content was not feasible. Mannitol GR allowed to prepare tablets only with granules containing 20% of drug, while granules prepared with mannitol PO permitted to achieve tablets up to 80% paracetamol, even if high roller compaction pressures were required and low mechanical resistant tablets were gained.