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Advanced process design and understanding of continuous twin-screw granulation via implementation of in-line process analytical technologies
Authors:Wei Meng  Andrés D Román-Ospino  Savitha S Panikar  Chris O&#x;Callaghan  Sean J Gilliam  Rohit Ramachandran  Fernando J Muzzio
Affiliation:1. Department of Pharmaceutics, Rutgers University, Piscataway, NJ 08854, USA;2. Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA;3. Innopharma Laboratories, Dublin 18, Ireland;4. Kaiser Optical Systems, Inc., Ann Arbor, MI 48103, USA
Abstract:Process analytical technologies (PAT) are identified as an essential element in the Quality by Design framework, providing the cornerstone to implement continuous pharmaceutical manufacturing. This study is concerned with employing three in-line PATs: Eyecon? 3D imaging system, Near-infrared spectroscopy (NIRS) and Raman spectroscopy (RS), in a continuous twin-screw granulation process to enable real-time monitoring and prediction of critical quality attributes of granules. The Thermo Scientific? Pharma 11 twin-screw granulator was used to manufacture granules from a low-dose formulation with caffeine anhydrous as the model drug. A 30-run full factorial design including three critical process parameters (liquid to solid ratio, barrel temperature and throughput) was conducted to evaluate the performance of each analytical tool. Eyecon? successfully captured the granule size and shape variation from different experimental conditions and demonstrated sufficient sensitivity to the fluctuation of size parameter D10 in the presence of process perturbations. The partial least square regression (PLSR) models developed using NIRS showed small relative standard error of prediction values (less than 5%) for most granule physical properties. In contrast, the RS-based PLSR models revealed higher prediction errors towards granule drug concentration, potentially due to the inhomogeneous premixing of raw materials during calibration model development.
Keywords:Continuous pharmaceutical manufacturing  Twin-screw granulation  Process analytical technology  Near-infrared spectroscopy  Raman spectroscopy
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