Implementing Feedback Granule Size Control in a Continuous Dry Granulation Line Using Controlled Impeller Speed of the Granulation Unit, Compaction Force and Gap Width

In continuous manufacturing of pharmaceuticals, dry granulation is of interest because of its large throughput capacity and energy efficiency. In order to manufacture solid oral dosage forms continuously, valid control strategies for critical quality attributes should be established. To this date, there are no published control strategies for granule size distribution in continuous dry granulation.

Methods
In-line laser diffraction was used to determine the size of granules in a continuous roll compaction/dry granulation line (QbCon® dry). Different process parameters were evaluated regarding their influences on granule size. The identified critical process parameters were then incorporated into control strategies. The uncontrolled and the controlled processes were compared based on the resulting granule size. In both processes, a process parameter was changed to induce a shift in median particle size and the controller had to counteract this shift.

Results
In principle, all process parameters that affect the median particle size could also be used to control the particle size in a dry granulation process. The sieve impeller speed was found to be well suited to control the median particle size as it reacts fast and can be controlled independently of the throughput or material.

Conclusion
The median particle size in continuous roll compaction can be controlled by adjusting process parameters depending on real-time granule size measurements. The method has to be validated and explored further to identify critical requirements to the material and environmental conditions.

Download the full article: Wilms2020_Article_ImplementingFeedbackGranuleSiz

or continue reading here: Wilms, A., Teske, A., Meier, R. et al. Implementing Feedback Granule Size Control in a Continuous Dry Granulation Line Using Controlled Impeller Speed of the Granulation Unit, Compaction Force and Gap Width. J Pharm Innov (2020). https://doi.org/10.1007/s12247-020-09524-3

Materials
Microcrystalline cellulose (MCC, Vivapur® 102, JRS Pharma, Germany) was used as a plastically deforming excipient in experiments studying varying process parameters. For various experiments, magnesium stearate (Parteck LUB MST, Merck, Germany) was added at 1% for lubrication. For studies using an API in a formulation, 25% Diclofenac (Amoli Organics Pvt. Ltd., India), 60% MCC and 14% anhydrous β-lactose (SuperTab® 21AN, DFE Pharma, Germany)