1.2    Increased activity in research of RC

In the past decades, research with regard to RC has concentrated on how different types of commonly used excipients behave during the RC process and how variability in the material properties (such as particle size, polymorphic form or moisture content) affect the processing and resulting end products.

Examples exist of single excipients, simple binary mixtures with actives or two excipients, and model formulations including the effect of lubrication during RC.

In the spirit of the process analytical technology (PAT) and other regulatory initiatives (such as Quality-by-Design), there has been an increased interest in understanding the process and material behavior during RC using sophisticated analytical tools, such as near-infrared spectroscopy. Gupta et al. have written a series of papers investigating realtime control of the RC process during the past few years.

However, already in the late 1990s there were examples of the successful application of PAT to RC using acoustic emission spectroscopy. For example, Salonen et al. measured acoustic relaxation emissions from microcrystalline cellulose and maize starch during the dry granulation process. Because, for a given formulation, the solid fraction is the most important parameter regarding ribbon properties, for example, compact strength, the simplest means of in-process control of granulate

properties is achieved by controlling the so-called ‘at gap’ density during RC by determining both the volume of compacted powder made per unit of time between the rolls (from gap,roll speed and roll width) and the corresponding amount of granulate prepared by continuously measuring the weight of granulate.