McAuliffe, MAP,O'Mahony, GE,Blackshields, CA,Collins, JA,Egan, DP,Kiernan, L,O'Neill, E,Lenihan, S,Walker, GM,Crean, AM

2015

January

Organic Process Research & Development

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

Published

()

PARTICLE-SIZE PHARMACEUTICAL APPLICATIONS COMPACTION/DRY GRANULATION CRUSHING STRENGTH TABLET PROPERTIES DISSOLUTION RATE TIME COMPRESSIBILITY COMPACTIBILITY SPECTROSCOPY

19

158

166

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.

10.1021/op5000013