Influence of powder stream density on near infrared measurements upon scale-up of a simulated continuous process.

Autor: Velez-Silva NL; Duquesne University Graduate School for Pharmaceutical Sciences, Pittsburgh, PA 15282, United States; Duquesne Center for Pharmaceutical Technology, Duquesne University, Pittsburgh, PA 15282, United States., Drennen JK 3rd; Duquesne University Graduate School for Pharmaceutical Sciences, Pittsburgh, PA 15282, United States; Duquesne Center for Pharmaceutical Technology, Duquesne University, Pittsburgh, PA 15282, United States., Anderson CA; Duquesne University Graduate School for Pharmaceutical Sciences, Pittsburgh, PA 15282, United States; Duquesne Center for Pharmaceutical Technology, Duquesne University, Pittsburgh, PA 15282, United States. Electronic address: andersonca@duq.edu.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Oct 15; Vol. 645, pp. 123354. Date of Electronic Publication: 2023 Aug 28.
DOI: 10.1016/j.ijpharm.2023.123354
Abstrakt: Near-infrared (NIR) spectroscopy is a powerful process analytical tool for monitoring chemical constituents in continuous pharmaceutical processes. However, the density variation introduced when quantitative NIR measurements are performed on powder streams at different flow rates is a potential source of a lack of model robustness. Since different flow rates are often required to meet the production requirements (e.g., during scale-up) of a continuous process, the development of efficient strategies to characterize, understand, and mitigate the impact of powder density on NIR measurements is highly desirable. This study focused on assessing the effect of powder physical variation on NIR by enabling the in-line characterization of powder stream density in a simulated continuous system. The in-line measurements of powder stream density were facilitated through a unique analytical interface to a flowing process. Powder streams delivered at various design levels of flow rate and tube angle were monitored simultaneously by NIR diffuse reflectance spectroscopy, live imaging, and dynamic mass characterization. Statistical analysis and multivariate modeling confirmed powder density as a significant source of spectral variability due to flow rate. Besides providing broader process understanding, results elucidated potential mitigation strategies to facilitate effective continuous process scale-up while ensuring NIR model robustness against density.
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 © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: