Description

The main focus of this research is to investigate the continuous high shear wet granulation process. Wet granulation is used broadly in the pharmaceutical industry. This technology has many advantages such as enhancing compression and powder handling, decreasing ingredient segregation and ensuring the content uniformity through binding of ingredients to each other. A high level of interest exists at the present time in the continuous version of this technology, both by the US FDA, and by large pharmaceutical manufacturers. Continuous manufacturing methods can provide significant technical and business advantages relative to batch methods. As has been demonstrated in other process industries, continuous manufacturing methods are more robust and controllable. They achieve the same production rates as batch processes in much smaller and thus less capital-intensive equipment. However, despite these advantages, the pharmaceutical industry still relies almost exclusively on traditional batch methods to produce tablets and capsules. In recent years, different continuous WG techniques have been investigated, such as fluid bed agglomeration and twin-screw extrusion. However, integration of these unit operations into a complete continuous tablet manufacturing line is still a bottleneck due to high production cost and poor understanding of impact of granule properties. In this work, a continuous high-shear wet granulation process is examined based on a placebo formulation comprising of 70% ∂-lactose monohydrate and 30% microcrystalline cellulose (Avicel PH101). The process includes two stages. As the powders are fed into the granulator, the blades mounted on the shaft will push the dry powders forward and promote both dispersive axial mixing and convective cross-sectional mixing. This is the mixing stage. The granulation stage occurs once the mixtures reach the nozzle location where a binding liquid (water) is fed via a pump. Then the granule size grows and decays due to nucleation, coalescence, consolidation and attrition or breakage. In this study, two process variables (rotation speed, L/S ratio) and two design parameters (blade configuration and nozzle position) are selected for the I-optimal design. The collected granules are dried in a hot-air convection oven to a desirable LOD (~ 3%). Granule properties, such as particle size distribution, flow properties, density, compaction and are measured. Batches with desirable particle size distribution are selected for further characterization. The rotation speed and L/S ratio have the most significant effects on the granule properties. The optimum operations of this granulation are 0.3 L/S ratio with the rotation speed of 275RPM or 660RPM.