The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing

Abstract

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to monitor continuous processes in real time is required to ensure product quality. This paper presents the application of novel process analytical technology (PAT) tools in combination with off-line analytical techniques for the study of a laboratory-scale roller compaction dry granulation process. An experiment whereby roll pressure was linearly increased and the effects thereof on roller compacted ribbon and granule properties of a placebo formulation is described. Analysis of the ribbons and granules was performed using both in-line and off-line techniques. Ribbon envelope density was measured using the GeoPyc, and the results were compared to off-line near-infrared (NIR) measurements and a novel in-line NIR tool, the Multieye. Particle size analysis of roller compacted granules was assessed with traditional sieve analysis, Camsizer and a novel technique, the Eyecon. Both Camsizer and Eyecon have the potential of being used as PAT tools in-line. Additionally the compressibility of the granules was determined using in-die Heckle analysis and the hardness of the resultant compacts was assessed. The compacts were subsequently analysed using off-line Raman spectroscopy to investigate the surface smoothness which was shown to indicate crushing strength for compacts prepared. The results of this initial study demonstrate a good relationship between in-line and off-line measurement of key in-process material attributes. The findings thus support the further exploitation of these new in-line PAT methods in monitoring of continuous unit operations at a commercial scale.

RTD-based material tracking in a fully-continuous dry granulation tableting line

“…Recent publications illustrate the benefits of the Quality by Design approach to process design (Heiman et al, 2015;Souihi et al, 2015Souihi et al, , 2013. In that context, the interest in PAT tools, such as NIR in process monitoring, has been increasing (McAuliffe et al, 2015;Quyet et al, 2013).…”

Using a Material Library to Understand the Impacts of Raw Material Properties on Ribbon Quality in Roll Compaction

“…In the literature [34,35,[51][52][53][54], it was demonstrated that the roll pressure was the most important process parameter that affected the resulting ribbons. In this paper, only the hydraulic pressure was considered as the critical process parameter (CPP) in order to fully understand the impacts of raw material properties on ribbon qualities.…”

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

“…This results in difficulties to measure the full product flow as well as obtaining a representative sample to measure [20]. Therefore, limited research has been published on RCDG and in-line/on-line particle sizing [31][32][33].…”