Batch and continuous processing in the production of pharmaceutical granules.

A quasicontinuous granulation and drying process to avoid scale-up problems is introduced in this work. Consistent and reproducible granule quality is a key factor in robust dosage form design and fits ideally the prerequisites of a drug quality system for the twenty-first century and the Food and Drug Administration's Process Analytical Technology (PAT) initiative. In scale-up, factors that simulate or reproduce the laboratory scale must be considered. This system provides a new possibility for industrial manufacturing and galenical development of pharmaceutical solids. The quasicontinuous method described in the present work, and the laboratory and production batches and the granulating equipment used to produce them, are the same. Once a robust process has been defined in the laboratory, it is merely repeated as many times as necessary to achieve the desired final batch size. The quasicontinuous process gives new possibilities to simplify manufacturing procedures and to validate them faster. The quality of the resulting granules and tablets compared with classical methods is equal until better. In many cases, existing products have been transferred to the multicell process without formulation changes. The quasicontinuous production concept for high-shear granulation and fluid-bed drying offers many advantages over the classical methods used to produce pharmaceutical granules. The wet massing process may be monitored by the power consumption of the mixer motor for each subunit, as in classical high-shear granulation processes. The air volume, temperature, and humidity of each of the drying cells may be controlled individually to avoid overheating of temperature-sensitive materials. All processing variables must be precisely controlled by a computer, and the data must be collected for documentation. As such, product quality and reproducibility for each subunit is assured.