Mechanistic modeling of twin screw wet granulation for pharmaceutical formulations: Calibration, sensitivity analysis, and model-driven workflow.

Autor: Bala N; Department of Chemical & Biological Engineering, University of Sheffield, UK., Corrigan J; Pfizer Inc, Sandwich, UK., Meyer J; Pfizer Inc, Sandwich, UK., Schongut M; Pfizer Inc, Sandwich, UK., Doshi P; Pfizer Inc, Sandwich, UK., Iyer K; Pfizer Inc, Sandwich, UK., Lee K; Pfizer Inc, Sandwich, UK., Rowland M; Pfizer Inc, Sandwich, UK., Litster JD; Department of Chemical & Biological Engineering, University of Sheffield, UK., Dawson N; Pfizer Inc, Sandwich, UK., Smith RM; Department of Chemical & Biological Engineering, University of Sheffield, UK. Electronic address: Rachel.smith@sheffield.ac.uk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jun 25; Vol. 659, pp. 124246. Date of Electronic Publication: 2024 May 20.
DOI: 10.1016/j.ijpharm.2024.124246
Abstrakt: Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in pharmaceutical manufacturing. In this study, a mechanistic-based population balance model is applied to twin screw wet granulation. This model incorporated a recently developed breakage kernel specifically designed for twin screw granulation, along with nucleation, layering, and consolidation. Calibration and validation were performed on Hydrochlorothiazide and Acetaminophen formulations, which exhibit different particle size and wettability characteristics. Utilizing a compartmental experimental dataset, a comprehensive global sensitivity analysis identified critical inputs impacting quality attributes. The study revealed that the nucleation rate process model, effectively represented particle size distributions for both formulations. Adjustments to nucleation and breakage rate parameters, influenced by material properties and screw configuration, improved the model's accuracy. A model-driven workflow was proposed, offering step-by-step guidelines and facilitating PBM model usage, providing essential details for future active pharmaceutical ingredient (API) formulations.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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