Process optimization of dry granulation based tableting line: Extracting physical material characteristics from granules, ribbons and tablets using near-IR (NIR) spectroscopic measurement

Abstract

Dry granulation using roller compaction is an important unit operation in the pharmaceutical industry. In contrast to many wet granulation techniques applied in pharmaceuticals, dry granulation is a continuous process and it is a suitable processing solution for moisture and heat-sensitive active compounds. During dry granulation, the powder is compacted between two rolls to form compacts (ribbons). These ribbons are subsequently milled into granules and finally, compressed into tablets. One of critical process parameters is the porosity of these ribbons critically influencing the granule properties and final product quality. In this work, model ribbons with varying porosity were prepared at different roll pressures and roll speeds. The ribbons were further milled to granules and these granules were compacted into tablets. Using near-infrared chemical imaging (NIR-CI) together with a chemometric data analysis as a surrogate method, we visualized the porosity distribution in the ribbons. It was also demonstrated that the particle size of milled granules could be estimated with a probe-based single-point NIR measurement. This information could be related to downstream processing, since ribbons with lower porosity resulted in granules with larger size and corresponding tablets from these larger granules had lower tensile strength. Our study confirms the potential of NIR-CI and NIR spectroscopy for process monitoring and control of continuously operating roller compaction line.