Blend uniformity monitoring in a continuous manufacturing mixing process for a low-dosage formulation using a stream sampler and near infrared spectroscopy.

Autor: Rangel-Gil RS; Department of Chemical Engineering, University of Puerto Rico at Mayaguez, Puerto Rico 00681, United States., Nasrala-Álvarez JM; Department of Chemical Engineering, University of Puerto Rico at Mayaguez, Puerto Rico 00681, United States., Romañach RJ; Department of Chemistry, University of Puerto Rico at Mayaguez, Puerto Rico 00681, United States., Méndez R; Department of Chemical Engineering, University of Puerto Rico at Mayaguez, Puerto Rico 00681, United States. Electronic address: rafael.mendez1@upr.edu.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Aug 15; Vol. 661, pp. 124478. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1016/j.ijpharm.2024.124478
Abstrakt: Continuous manufacturing has the potential to offer several benefits for the production of oral solid dosage forms, including reduced costs, low-scale equipment, and the application of process analytical technology (PAT) for real-time process control. This study focuses on the implementation of a stream sampler to develop a near infrared (NIR) calibration model for blend uniformity monitoring in a continuous manufacturing mixing process. Feeding and mixing characterizations were performed for three loss-in-weight feeders and a commercial continuous mixer to prepare powder blends of 2.5-7.5 % w/w ibuprofen DC 85 W with a total throughput of 33 kg/h. The NIR spectral acquisition was performed after the mixing stage using a stream sampler for flowing powders. A continuous mixer shaft speed of 250 RPM was selected to operate the mixing process based on a variability analysis developed with in-line spectral data acquired using the stream sampler at 6 RPM. A partial least squares regression (PLS-R) model was performed and evaluated, yielding a root-mean-square error of prediction (RMSEP) of 0.39 % w/w and a bias of 0.05 % w/w. An independent experimental run conducted two days later revealed that the continuous mixing process and the NIR calibration model presented low day-to-day variation. The minimum practical error (MPE) and sill values through variographic analysis showed low variance associated with the sampling process using the stream sampler. Results demonstrated the promising capacity of the stream sampler coupled to an NIR probe to be implemented within continuous manufacturing processes for the real-time determination of API concentration.
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 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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