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Blend uniformity monitoring in a continuous manufacturing mixing process for a low-dosage formulation using a stream sampler and near infrared spectroscopy
Peer-reviewed journal | 19 Jul 2024 | Contributor(s):: Rodolfo Romanach, Raúl S. Rangel-Gil, Juan M. Nasrala-Álvarez, Rafael Méndez
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...
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Development and Application of Control Concepts for Twin-Screw Wet Granulation in the ConsiGmaTM-25: Part 2 Granule Size
Peer-reviewed journal | 04 Jun 2024 | Contributor(s):: Selma Celikovic, Johannes Poms, Johannes Khinast, Martin Horn, Jakob Rehrl
Traditional operation modes, such as running the production processes at constant process settings or within a narrow design space, do not fully exploit the advantages of continuous pharmaceutical manufacturing. Integrating Quality by Control (QbC) algorithms as a standard component of...
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Variographic analysis: A new methodology for quality assurance of pharmaceutical blending processes
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Sánchez-Paternina, Adriluz, Sierra-Vega, Nobel O., Cárdenas, Vanessa, Méndez, Rafael, Esbensen, Kim H., Romañach, Rodolfo J.
Analytical methods for real time monitoring of pharmaceutical blending processes are thoroughly validated but not the sampling methods. Variographic analysis was investigated as a method to determine the sampling and analytical errors when the drug concentration of pharmaceutical powder blends is...
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WHAT are sampling errors-and WHAT can we do about them? Part 1
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Romañach, Rodolfo J., Joubert Castro, Aidalu, Esbensen, Kim H
The objective of this column is to provide easy-to-understand examples of sampling errors. Prompted by recent participationsand presentations at on-line conferences and meetings, we believe there is a need for a more fulfilling introduction andexemplification of the concept and real-world...
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Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: Influence of mass flow and rotation speed variations
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Martínez, Lizbeth, Peinado, Antonio, Liesum, Lorenz, Betz, Gabriele
The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender. For this purpose, a NIR diode array spectrometer with fast data acquisition was selected. Additionally, the dynamic...
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Use of Terahertz-Raman Spectroscopy to Determine Solubility of the Crystalline Active Pharmaceutical Ingredient in Polymeric Matrices during Hot Melt Extrusion
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Bordos, E, Islam, MTFlorence, AJ, Halbert, GW, Robertson, J
Polymer-based amorphous solid dispersions (ASDs) comprise one of the most promising formulation strategies devised to improve the oral bioavailability of poorly water-soluble drugs. Exploitation of such systems in marketed products has been limited because of poor understanding of physical...
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Using PAT to accelerate the transition to continuous API manufacturing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Gouveia, Francisca, Rahbek, Jesper, Mortensen, Asmus, Pedersen, Mette, Felizardo, Pedro, Bro, Rasmus, Mealy, Michael
Significant improvements can be realized by converting conventional batch processes into continuous ones. The main drivers include reduction of cost and waste, increased safety, and simpler scale-up and tech transfer activities. Redesigning the process layout offers the opportunity to incorporate...
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Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Engisch, William, Muzzio, Fernando
Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing,...
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Toward Continuous Crystallization of Urea-Barbituric Acid: A Polymorphic Co-Crystal System
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Powell, KA, Bartolini, GWittering, KE, Saleemi, AN, Wilson, CC, Rielly, CD, Nagy, ZK
Pharmaceutical co-crystals are multicomponent molecular systems typically formed through hydrogen bonding of a co-former molecule with the active pharmaceutical ingredient (API). Just as many single component molecular structures can exhibit polymorphism due to the geometry of hydrogen bond...
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Towards 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Sagandira, CR, Nqeketo, SMhlana, K, Sonti, T, Gaqa, S, Watts, P
Continuous flow chemistry has opened a new paradigm in both the laboratory and pharmaceutical industry. This review details the recently reported literature on continuous multistep telescoped synthesis of active pharmaceutical ingredients (APIs), inline flow downstream processing, in-process...
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Towards a novel continuous HME-Tableting line: Process development and control concept
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Sacher, Stephan, Celikovic, Selma, Rehrl, Jakob, Poms, Johannes, Kirchengast, Martin, Kruisz, Julia, Sipek, Martin, Salar-Behzadi, Sharareh, Berger, Hannes, Stark, Gerald, Horn, Martin, Khinast, Johannes G.
The objective of this study was to develop a novel closed-loop controlled continuous tablet manufacturing line, which first uses hot melt extrusion (HME) to produce pellets based on API and a polymer matrix. Such systems can be used to make complex pharmaceutical formulations, e.g., amorphous...
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The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Dadou, SM, Tian, YWLi, S, Jones, DS, Andrews, GP
Complications associated with uncontrolled hypertension are considered the major cause of premature death worldwide. Fixed-dose combinations (FDCs) offer an alternative approach to polypharmacy with the aim to improve patient compliance. Process Analytical Technology (PAT) is gaining momentum as...
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The scope of PAT in real-time advanced control of tablet quality
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit
Continuous pharmaceutical manufacturing together with process analytical technology (PAT) provides a suitable platform for automatic feed-forward/feed-back (FF/FB) control of the end product quality as desired by quality by design (QbD)-based efficient manufacturing. The precise control of the...
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The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T
Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...
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The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: McAuliffe M.A.P., Omahony G.E., Blackshields C.A., Collins J.A., Egan D.P., Kiernan L., Oneill E., Lenihan S., Walker G.M., Crean A.M.
Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to...
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The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Andres, G.P., Jones D.S., Senta-Loys Z., Almajaan A., Li S., Chevallier O., Elliot C., Healy A.M., Kelleher J.F., Madi A.M., Gilvary G.C., Tian Y.a
Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To...
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The Future of Pharmaceutical Manufacturing Sciences
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Rantanen, Jukka, Khinast Johannes
The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is...
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The Application of an Automated Control Strategy for an Integrated Continuous Pharmaceutical Pilot Plant
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Lakerveld, R, Benyahia, BHeider, PL, Zhang, HT, Wolfe, A, Testa, CJ, Ogden, S, Hersey, DR, Mascia, S, Evans, JMB, Braatz, RD, Barton, PI
Continuous manufacturing offers potential opportunities for the improved manufacturing of pharmaceutical products. A key challenge is the development of an appropriate control strategy. The experimental application of an automated control strategy is presented for an end-to-end continuous...
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The Current Scientific and Regulatory Landscape in Advancing Integrated Continuous Biopharmaceutical Manufacturing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Adam C Fisher, Mark-Henry Kamga, Cyrus Agarabi, Kurt Brorson, Sau L Lee, Seongkyu Yoon
There is a trend across the pharmaceutical sector toward process intensification and continuous manufacturing to produce small-molecule drugs or biotechnology products. For biotechnology products, advancing the manufacturing technology behind upstream and downstream processes has the potential to...
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The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Dadou, Suha, Senta-Loys, Zoe, Almajaan, Ammar, Li, Shu, Jones, David, Healy, Anne, Tian, Yiwei, Andrews, Gavin
Continuous processing is superseding conventional batch processing as a means of manufacturing within the pharmaceutical Research Article/industry. This paradigm shift has led to the implementation of Process Analytical Technology (PAT) as a semi-automatic, predictive tool offering real-time...
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Study of near Infrared Chemometric Models with Low Heterogeneity Films: The Role of Optical Sampling and Spectral Preprocessing on Partial Least Squares Errors
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Ortega-Zuñiga, Carlos, Reyes-Maldonado, Kerimar, Méndez, Rafael, Romañach, Rodolfo J.
This study is focused on understanding absorption and scattering effects and their impact on the errors observed in near infrared calibration models developed using partial least squares regression able to predict the number of polypropylene film layers stacked together. The films provided a...
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Supervised Extended Iterative Optimization Technology for Estimation of Powder Compositions in Pharmaceutical Applications: Method and Lifecycle Management
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Muñoz, Salvador García, Torres, Eduardo Hernández
Further enhancements to the extended iterative optimization technology (EIOT) method are presented. These are meant to include the effects of nonchemical interferences of known origin in the EIOT parameters and to manage the lifecycle of the method in a pharmaceutical manufacturing application. A...
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Supervisory Control System for Monitoring a Pharmaceutical Hot Melt Extrusion Process
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Markl, Daniel, Wahl, Patrick R, Menezes, José C, Koller, Daniel M, Kavsek, Barbara, Francois, Kjell, Roblegg, Evaa, Khinast, Johannes G.
Continuous pharmaceutical manufacturing processes are of increased industrial interest and require uni- and multivariate Process Analytical Technology (PAT) data from different unit operations to be aligned and explored within the Quality by Design (QbD) context. Real-time pharmaceutical process...
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Small-Volume Continuous Manufacturing of Merestinib. Part 1. Process Development and Demonstration
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Cole, KP, Reizman, BJHess, M, Groh, JM, Laurila, ME, Cope, RF, Campbell, BM, Forst, MB, Burt, JL, Maloney, TD, Johnson, MD, Mitchell, D, Polster, CS, Mitra, AW, Boukerche, M, Conder, EW, Braden, TM, Miller, RD, Heller, MR, Phillips, JL, Howell, JR
Development of a small volume continuous process that used a combination of batch and flow unit operations to manufacture the small molecule oncolytic candidate merestinib is described. Continuous processing was enabled following the identification and development of suitable chemical...
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Small-Volume Continuous Manufacturing of Merestinib. Part 2.Technology Transfer and cGMP Manufacturing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Reizman, Brandon J., Hess, Molly, Burt, Justin L., Maloney, Todd D., Johnson, Martin D., Laurila, Michael E., Cope, Richard F., Luciani, Carla V., Buser, Jonas Y., Campbell, Bradley M., Forst, Mindy B., Mitchell, David, Braden, Timothy M., Lippelt, Christopher K., Boukerche, Moussa, Starkey, Derek R., Miller, Richard D., Chen, Jing, Sun, Baoquan, Kwok, Martin, Zhang, Xin, Tadayon, Sam, Huang, Ping
Technology transfer of a small volume continuous (SVC) process and Current Good Manufacturing Practices (cGMP) manufacturing of merestinib are described. A hybrid batch-SVC campaign was completed at a contract manufacturing organization under cGMP. The decision process by which unit operations...