Optimization of residence time distribution in RCDG and an assessment of its applicability in continuous manufacturing

Knowledge of residence time is a critical aspect in developing control and material diversion strategies for continuous manufacturing processes in pharmaceutical manufacturing. Dry granulation is a promising continuous granulation technique as it is fast and economical. In this study, a step-change method to determine residence time in roll compaction/dry granulation is introduced.

Highlights

A robust method to determine the residence time in roll compaction/dry granulation was established based on image analysis.

The effect of roll and impeller speed in the granulation unit was statistically analyzed in a central composite circumscribed design of experiments.

The impact of fill level in the hopper of the roll compactor was evaluated and compared to the behavior of continuous feeders/blenders.

Results were evaluated for the effect they would have on a continuous process with an out-of-specification event.

The factors roll speed and rotational speed of the impeller in the powder inlet unit of the compactor were evaluated using a central composite circumscribed statistical design of experiments in order to optimize the residence time. The fill volume in the compactor was varied exemplarily. It was found that high roll speed, low rotational speed of the impeller and low fill volume in the compactor are beneficial to generate fast transition through the compactor. The impact of roll speed increase was estimated. It can be concluded that despite fast residence time in the process, high roll speed and its subsequent high material throughput can generate a large amount of material that has to be discarded if material diversion is required. More on Optimization of residence time distribution in RCDG and an assessment of its applicability in continuous manufacturing

Keywords Roll compaction/dry granulation, Residence time distribution, Continuous manufacturing, Digital image analysis, Response surface optimization, Vivapur 102, Amaranth