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Robustness of a continuous direct compression line against disturbances in feeding
Contributor(s):: Karttunen A.-P., Poms J., Sacher S., Sparén A., Ruiz Samblás C., Fransson M., Martin De Juan L., Remmelgas J., Wikström H., Hsiao W.-K., Folestad S., Korhonen O.
The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances. These disturbances mimicked typical variations that can be encountered during long-term...
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Roller compaction: Infrared thermography as a PAT for monitoring powder flow from feeding to compaction zone
Contributor(s):: Yu, Mingzhe, Omar, Chalak, Weidemann, Marcus, Schmidt, Alexander, Litster, James D., Salman, Agba D.
Roller compaction is a continuous dry granulation process, in which powder is compressed by two counter-rotating rollers. During this process, the powder feeding to the compaction zone has a significant effect on product quality. This work investigates the flow of powder from the feeding zone to...
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Rolling phenomenon in twin screw granulation with controlled-release excipients
Contributor(s):: Thompson, M. R., O'Donnell, K. P.
The developed knowledge regarding use of twin screw granulators for continuous wet granulation has been primarily limited to immediate release formulations in the literature. The present study highlights an issue previously unreported for wet granulation with twin screw extruders when using...
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RTD modeling of a continuous dry granulation process for process control and materials diversion
Contributor(s):: Kruisz, Julia, Rehrl, Jakob, Sacher, Stephan, Aigner, Isabella, Horn, Martin, Khinast, Johannes G., Krumme, Markus
Disturbance propagation during continuous manufacturing processes can be predicted by evaluating the residence time distribution (RTD) of the specific unit operations. In this work, a dry granulation process was modelled and four scenarios of feeding events were simulated. We performed...
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Recent progress in continuous manufacturing of oral solid dosage forms
Contributor(s):: Vanhoorne, Valérie, Vervaet, Chris
Continuous drug product manufacturing is slowly being implemented in the pharmaceutical industry. Although the benefits related to the quality and cost of continuous manufacturing are widely recognized, several challenges hampered the widespread introduction of continuous manufacturing of drug...
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Residence Time Distribution (RTD)-Based Control System for Continuous Pharmaceutical Manufacturing Process
Contributor(s):: Bhaskar, Aparajith, Singh, Ravendra
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Real-time feedback control of twin-screw wet granulation based on image analysis
Contributor(s):: Madarasz, Lajos, Hoffer, Istvan, Szabo, Barnabas, Csontos, Istvan, Pataki, Hajnalka, Demuth, Balazs, Szabo, Bence, Csorba, Kristof, Nagy, Zsombor Kristof, Marosi, Gyorgy
The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored...
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Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy
Contributor(s):: Vanarase, Aditya, Alcalà, Manel, Jerez-Rozo, Jackeline, Muzzio, Fernando, Romañach, Rodolfo
A non-destructive NIR spectroscopic method was used to acquire on-line spectra of a continuous mixing process, and evaluate the performance of this novel system. Partial least squares (PLS) calibration models were developed and used for real-time determination of active ingredient concentration...
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Real-time monitoring of particle size distribution in a continuous granulation and drying process by near infrared spectroscopy
Contributor(s):: Pauli, V, Roggo, YKleinebudde, P, Krumme, M
In continuous granulation, it can be important to control granules particle size distribution (PSD), as it may affect final product quality. Near infrared spectroscopy (NIRS) is already a routine analytical procedure within pharmaceutical continuous manufacturing for the in-line analysis of...
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Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process
Contributor(s):: Huang, Yan-Shu, Medina-González, Sergio Straiton, Benjamin Keller, Joshua, Marashdeh, Qussai, Gonzalez, Marcial, Nagy, Zoltan, Reklaitis, Gintaras V.
While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the...
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Real-Time Monitoring of Powder Mixing in a Convective Blender Using Non-Invasive Reflectance NIR Spectrometry
Contributor(s):: Bellamy, L. J., Littlejohn, D., Nordon, A.
A convective blender based on a scaled down version of a high shear mixer-granulator was used to produce binary mixtures of microcrystalline cellulose (Avicel) and aspirin, citric acid, aspartame or povidone. Spectra of stationary Avicel or aspirin powder provided an indication of the information...
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Real-Time Quantification of Low-Dose Cohesive Formulations within a Sampling Interface for Flowing Powders
Contributor(s):: Sierra-Vega, Nobel. O., Romañach, Rodolfo J., Mendez, Rafael
This study investigates the performance of a sampling interface for monitoring cohesive, flowing powder formulations with Hausner's Ratio and Carr's Index higher than 1.5 and 35%, respectively. The sampler device was operated in combination with near-infrared (NIR) spectroscopy to quantify...
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Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing
Contributor(s):: Esmonde-White, Karen A, Cuellar, Maryann, Uerpmann, Carsten, Lenain, Bruno., Lewis, Ian R.
Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data...
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Raman Spectroscopy for Process Analytical Technologies of Pharmaceutical Secondary Manufacturing
Contributor(s):: Nagy, Brigitta, Farkas, Attila, Borbás, Enikő, Vass, Panna, Nagy, Zsombor Kristóf, Marosi, György
As the process analytical technology (PAT) mindset is progressively introduced and adopted by the pharmaceutical companies, there is an increasing demand for effective and versatile real-time analyzers to address the quality assurance challenges of drug manufacturing. In the last decades, Raman...
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Real time monitoring of powder blend bulk density for coupled feed-forward/feed-back control of a continuous direct compaction tablet manufacturing process
Contributor(s):: Singh, Ravendra, Román-Ospino, Andrés D. Romañach, Rodolfo J. Ierapetritou, Marianthi, Ramachandran, Rohit
The pharmaceutical industry is strictly regulated, where precise and accurate control of the end product quality is necessary to ensure the effectiveness of the drug products. For such control, the process and raw materials variability ideally need to be fed-forward in real time into an automatic...
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Real-time assessment of critical quality attributes of a continuous granulation process
Contributor(s):: Fonteyne, Margot, Vercruysse, Jurgen, Díaz, Damián Córdoba, Gildemyn, Delphine, Vervaet, Chris, Remon, Jean Paul, De Beer, Thomas
There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories,...
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Process optimization for continuous extrusion wet granulation
Contributor(s):: Tan, L, Carella, AJ, Ren, YK, Lo, JB
Three granulating binders in high drug-load acetaminophen blends were evaluated using high shear granulation and extrusion granulation. A polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl...
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Provoking an end-to-end continuous direct compression line with raw materials prone to segregation
Contributor(s):: Lakio, Satu, Ervasti, Tuomas, Tajarobi, Pirjo, Wikstrom, Hakan, Fransson, Magnus, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Folestad, Staffan, Abrahmsen-Alami, Susanna, Korhonen, Ossi
Continuous manufacturing of solid oral dosage forms is promising for increasing the efficiency and quality of pharmaceutical production and products. In this study a whole train continuous direct compression (CDC) line has been provoked using challenging formulations typically prone to...
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Qualitative Assessment of a Multi-Scale, Compartmental PBM-DEM Model of a Continuous Twin-Screw Wet Granulation Process
Contributor(s):: Barrasso, Dana, Ramachandran, Rohit
Wet granulation processes play a crucial role in solid oral dosage manufacturing processes. However, they are often designed empirically with poor efficiency. To implement quality-by-design, a more scientific understanding is desired to predict the effects of process and equipment design and...
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Quality Risk Assessment and Mitigation of Pharmaceutical Continuous Manufacturing Using Flowsheet Modeling Approach
Contributor(s):: Tian, Geng;, Koolivand, Abdollah, Arden, Nilou S., Lee, Sau, O'Connor, Thomas F.
Integrated flowsheet modeling is an engineering approach that can provide a framework for understanding the impact of process dynamics on drug quality and associated risks during production, thereby facilitating the development of robust continuous processes. In this investigation, flowsheet...
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Quality-by-Design III: Application of Near-Infrared Spectroscopy to Monitor Roller Compaction In-process and Product Quality Attributes of Immediate Release Tablets
Contributor(s):: Kona, Ravikanth, Fahmy, Raafat M., Claycamp, Gregg, Polli, James E., Martinez, Marilyn, Hoag, Stephen W.
The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller...
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Process monitoring and evaluation of a continuous pharmaceutical twin-screw granulation and drying process using multivariate data analysis
Contributor(s):: Silva, A. F., Vercruysse, J., Vervaet, C., Remon, J. P., Lopes, J. A., De Beer, T., Sarraguca, M. C.
The present study aims at acquiring an in-depth process knowledge about a twin-screw granulation and fluid bed drying process performed on the commercially available continuous line. Batch Statistical Process Monitoring (BSPM) principles are used to describe and monitor the variables with a...
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Process Analytical Technology for continuous manufacturing of solid-dosage forms
Contributor(s):: Fonteyne, Margot;, Vercrusysse, Jurgen, De Leersnyder, Fien, Van Snick, Bernd, Vervaet, Chris, Remon, Jean, De Beer, Thomas
Currently, pharmaceutical production is making the switch from batch processing towards continuous processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the...
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Process analytical technology for continuous manufacturing tableting processing: A case study
Contributor(s):: Pauli, Victoria, Pellegatti, Laurent, Nguyen Trung, Nhat Quang, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Roggo, Yves, Krumme, Markus
The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...
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Process analytical technology in continuous manufacturing of a commercial pharmaceutical product
Contributor(s):: Vargas, Jenny, Nielsen, Sarah, Cárdenas, Vanessa, Gonzalez, Anthony, Aymat, Efrain, Almodovar, Elvin, Classe, Gustavo, Colón, Yleana, Sanchez, Eric, Romañach, Rodolfo
The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial...