Advanced process design and understanding of continuous twin-screw granulation via implementation of in-line process analytical technologies

Wei Meng, Andrés D. Román-Ospino, Savitha S. Panikar, Chris O'Callaghan, Sean J. Gilliam, Rohit Ramachandran, Fernando Muzzio

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)879-894
Number of pages16
JournalAdvanced Powder Technology
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Granulation
Process design
Near infrared spectroscopy
Raman spectroscopy
Granulators
Pharmaceutical Preparations
Caffeine
Imaging systems
Drug products
Raw materials
Physical properties
Throughput
Calibration
Monitoring
Liquids
Temperature

All Science Journal Classification (ASJC) codes

  • Chemical Engineering(all)
  • Mechanics of Materials

Keywords

  • Continuous pharmaceutical manufacturing
  • Near-infrared spectroscopy
  • Process analytical technology
  • Raman spectroscopy
  • Twin-screw granulation

Cite this

Meng, Wei ; Román-Ospino, Andrés D. ; Panikar, Savitha S. ; O'Callaghan, Chris ; Gilliam, Sean J. ; Ramachandran, Rohit ; Muzzio, Fernando. / Advanced process design and understanding of continuous twin-screw granulation via implementation of in-line process analytical technologies. In: Advanced Powder Technology. 2019 ; Vol. 30, No. 4. pp. 879-894.
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Advanced process design and understanding of continuous twin-screw granulation via implementation of in-line process analytical technologies. / Meng, Wei; Román-Ospino, Andrés D.; Panikar, Savitha S.; O'Callaghan, Chris; Gilliam, Sean J.; Ramachandran, Rohit; Muzzio, Fernando.

In: Advanced Powder Technology, Vol. 30, No. 4, 01.04.2019, p. 879-894.

Research output: Contribution to journalArticle

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