In-line Size Monitoring of a Twin Screw Granulation Process Using High-Speed Imaging

This study aimed to evaluate the feasibility of implementing a 3D high-speed imaging camera for in-line monitoring of a continuous wet granulation process and its potential for real-time process control. The Eyecon(TM) camera was used for monitoring a twin screw granulated-placebo formulation composed of lactose (73.5 %), microcrystalline cellulose (20 %), hydroxypropylmethyl cellulose (5 %), and croscarmellose sodium (1.5 %). Water was used as the granulating liquid at liquid-to-solid (L/S) ratios from 0.15 to 0.35 at 0.05 increments. The lactose particle size was varied using three grades of lactose: pharmatose 200 M, impalpable, and SuperTab 30GR. The process was perturbed by changing the L/S ratio, while monitoring the process using the camera. A Shewhart control chart was constructed using control limits obtained under steady-state conditions. Statistical process control tools were used to assess the implications of choosing different quality characteristics on the detectability of process shifts. The camera showed sensitivity to variation in process parameters, which was evident in the calculated granule size and particle count. Larger particles had strong leverage on the converted volume distribution, which significantly affected the magnitude of variability in the statistics of particle diameters. It was shown that particle count and d (10) were more sensitive to process shifts than d (50) and d (90). The sensitivity of the high-speed camera, coupled with image analysis, to process perturbations and the variety of generated characteristics of particle attributes demonstrate the potential of this technique for continuous process monitoring and control.