Evaluation of an in-line particle imaging tool for monitoring twin-screw granulation performance

Abstract

Twin-screw granulation is an emerging continuous wet granulation technique in the pharmaceutical industry due to several advantages over batch granulation. However, for the implementation of a fully continuous line in an industrial environment, in-process measurement tools are required to monitor critical process parameters and (intermediate) product quality attributes, and trigger control actions based on such measurements. This study aimed at evaluating the feasibility of implementing an in-line particle imaging technique (Eyecon™) after continuous twin-screw granulation and before the drying system. Off-line sieving was used as reference particle size analysis method. A twin-screw granulator which is part of the Consigma system was used to granulate a placebo formulation composed of lactose and polyvinylpyrrolidone (PVP; 97.5:2.5% w/w). PVP was dissolved in water, which was used as granulation liquid at liquid-to-solid ratios ranging between 8 and 9%. The performance of the in-line measurement method at heterogeneous process conditions was tested by changing the liquid to solid ratio (8–9%), the material throughput (10–25kg/h) and the screw configuration (1×6 and 2×6 kneading discs). The volumetric size distribution obtained from the in-line measurements of the granules leaving the twin-screw granulator using the Eyecon™ camera was compared with the off-line measurements obtained by sieving of the granule samples collected before and after the drying unit operation. For the intermediate size range (diameter 250–1000μm), the Eyecon™ measurements showed to be promising as they were in agreement with off-line measurement results obtained before the drying unit. However, the image analysis algorithm and data post-processing of the Eyecon™ images for the fines and oversized ranges require modification for improvement in measurement results. In conclusion, the Eyecon™ provides very good in-line images despite a dense moving flow of granules. However, proper analysis of these images is crucial before application as standard in-line particle size monitoring tool and application for control purposes can be realized.