Rangel Gil, Raúl Steven

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    Implementation of a stream sampler for real-time blend uniformity monitoring using near-infrared and raman spectroscopy
    (2024-05-06) Rangel Gil, Raúl Steven; Méndez Román, Rafael; College of Engineering; Acevedo Rullán, Aldo; Romañach, Rodolfo J.; Department of Chemical Engineering; Del Pilar Albaladejo, Joselyn
    This work describes the advancements of the implementation of the stream sampler along with Process Analytical Technology (PAT) for real-time monitoring of blend uniformity in batch and continuous manufacturing processes of tablets. This work describes two different stream sampler implementations. The first one (Chapter 2) describes the first implementation of the Raman spectrometer in the stream sampler to monitor low drug concentration in poor flowability powder blends. Raman spectra were continuously acquired as the powder blends flowed through the stream. A calibration model was developed to quantify caffeine concentration from 1.50 to 4.50% w/w. Caffeine concentration was predicted for the test set blends with a root mean square error of prediction of 0.21% w/w and a low bias of -0.03% w/w. The results showed the ability of the Raman spectrometer coupled with the stream sampler to monitor low drug concentration for poor flowability blends. The Second (Chapter 3) presents the implementation of the stream sampler device to develop a 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 device for flowing powders. 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. Results demonstrated the promising capacity of the stream sampler coupled to a NIR probe to be implemented within continuous manufacturing processes for the real-time determination of API concentration. This study contributes to a better understanding of the analysis of Raman spectra obtained through the use of the stream sampler. Furthermore, this thesis provides insights into the implementation of the stream sampler to perform a mixing characterization to find the adequate blending speed in a continuous manufacturing process. The outcomes of this research can be used to integrate, characterize, and optimize the stream sampler for blend uniformity monitoring, whether in batch or a continuous manufacturing process.