Process control and scale-up of pharmaceutical wet granulation processes: a review

Abstract

In this paper the techniques for process control and scale-up of pharmaceutical wet granulation processes are reviewed. For wet granulation in high-shear mixers, specific methods based on the liquid saturation and the consistency of the wet mass are described. Both parameters can be used to quantify the deformability of the wet granules, and relate well with the particle size of the end granules. In practice, the power consumption of the high-shear mixer is used for the monitoring of the wet granulation process, whilst for scale-up, it is helpful to use the underlying relationship between power consumption and saturation level or wet mass consistency. In fluid bed granulation the granulation process is different and the moisture content in the bed is the key parameter to control. This can be monitored directly by near infrared probes or indirectly with temperature probes. As a large number of inter-related variables can be adjusted to modify the process, computerized techniques have become popular for fluid-bed process control – fuzzy logic, neural networks, and models based on experimental design techniques are several examples. In addition, engineering techniques based on particle size population balance modelling are under development for both fluid bed and high-shear granulation.