Development and Evaluation of an In-line and On-line Monitoring System for Granule Size Distributions in Continuous Roll Compaction/Dry Granulation Based on Laser Diffraction

Scheme of a RCDG, in-and on-line laser diffraction

Roll compaction/dry granulation is established in manufacturing of solid oral dosage forms and, within the context of continuous manufacturing, it has sparked interest as material is fed, processed, and ejected continuously while also providing large possible throughputs. However, this amount of material has to be adequately controlled in real time to assure quality.

Methods
This research aimed at monitoring the critical quality attribute granule size distribution in continuous roll compaction/ dry granulation (QbCon®; L.B. Bohle, Ennigerloh, Germany) using in-line and on-line laser diffraction. The influence of varying process parameters and excipient formulations was studied and evaluated with the prospect of using this technique to develop control loops. For this purpose, residence time parameters were assessed. In- and on-line data was compared with off-line laser diffraction and dynamic image analysis data.

Results
The system successfully monitored the granule size distribution in a variety of process parameters and throughputs (up to 27.5 kg/h). It was sensitive to changes in process parameters and changes in material blends, which could pose a potential threat to the final drug products’ quality. Average event propagation time from the compaction zone to the laser diffraction system of 17.7 s demonstrates the systems’ fast reaction time.

Importance of β-cyclodextrin substitution level and type for solubilization and stabilization of poorly soluble APIs in parenteral dosage forms

Inclusion complex of 2-phenylethanol in β-cyclodextrin: preparation, characterization, computational study and evaluation of antinociceptive activity

Design, Optimization, and Characterization of Zolmitriptan Loaded Liposomal Gels for Intranasal delivery for acute migraine therapy

Conclusion
Results highlight laser diffraction as a valuable method of in- and on-line size determination and allow for the development of a control strategy using this principle.

Download the publication here: Development and Evaluation of an In-line and On-line Monitoring System for Granule Size Distributions in Continuous Roll Compaction:Dry Granulation Based on Laser Diffraction

Journal of Pharmaceutical Innovation
https://doi.org/10.1007/s12247-020-09443-3
Annika Wilms, Robin Meier & Peter Kleinebudde

excipients formulation