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The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration
23 Jul 2024 | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.
Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...
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Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients
23 Jul 2024 | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J
This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...
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Process analytics for the new era of continuous RNA manufacturing
23 Jul 2024 | Contributor(s): Botonjic-Sehic, Edita
In this article, Edita Botonjic-Sehic, Head of Process Analytics and Data Science at ReciBioPharm, examines the need for a digitally controlled continuous manufacturing process to correct the shortcomings of the current standard of batch processing. She highlights the critical role in-line...
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Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant
09 Jul 2024 | Peer-reviewed journal | Contributor(s): Johannes Khinast, Martin Horn, Jakob Rehrl, Selma Celikovic, Johannes Poms
ConsiGmaTM-25 is a continuous production plant integrating a twin-screw granulation, fluid bed drying, granule conditioning, and a tableting unit. The particle size distribution (PSD), active pharmaceutical ingredient (API) content, and liquid content of wet granules after twin-screw...
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Continuous Flow Intensification for the Synthesis of High-Purity Warfarin
10 May 2024 | Peer-reviewed journal | Contributor(s): Silva-Brenes, Diana V., Reyes-Vargas, Stephanie K., Duconge, Jorge, Vlaar, Cornelis, Stelzer, Torsten, Monbaliu, Jean-Christophe M.
While racemic warfarin was initially commercialized as a rodenticide, it has become the most prescribed anticoagulant drug for prevention of blood clots and is part of the World Health Organization’s list of essential medicines. The synthesis of warfarin appears straightforward, consisting of a...
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Rapid production of the anaesthetic mepivacaine through continuous, portable technology
24 Apr 2024 | Peer-reviewed journal | Contributor(s): Díaz-Kruik, Pablo, Paradisi, Francesca
Local anaesthetics such as mepivacaine are key molecules in the medical sector, so ensuring their supply chain is crucial for every health care system. Rapid production of mepivacaine from readily available commercial reagents and (non-dry) solvents under safe conditions using portable,...
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Multi-step Flow Synthesis of the Anthelmintic Drug Praziquantel
24 Apr 2024 | Peer-reviewed journal | Contributor(s): Phull, Manjinder Singh, Bohara, Chander Singh, Gundla, Rambabu, Mainkar, Prathama S., Jadav, Surender Singh
Praziquantel (PZQ; Brand name: Biltricide) is categorized as an anthelminthic drug, and it is used for the treatment of Schistosomiasis and other parasitic infections. The World Health Organization (WHO) has classified it as one of the essential and emergency medicines needed across the globe....
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Continuous Flow-Facilitated CB2 Agonist Synthesis, Part 2: Cyclization, Chlorination, and Amination
24 Apr 2024 | Peer-reviewed journal | Contributor(s): Prieschl, Michael, Sagmeister, Peter, Moessner, Christian, Sedelmeier, Joerg, Williams, Jason D., Kappe, C. Oliver
A new route to the cannabinoid receptor type 2 agonist, RG7774, has been developed circumventing an alkylation with poor regioselectivity as the final step. In the new synthetic route, this side chain is incorporated from the beginning. In this article, the development of the final four...
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Automated and continuous synthesis of drug substances
24 Apr 2024 | Peer-reviewed journal | Contributor(s): Sacher, Stephan, Castillo, Ismael, Rehrl, Jakob, Sagmeister, Peter, Lebl, René, Kruisz, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D., Kirschneck, Dirk, Kappe, C. Oliver, Horn, Martin
A continuous synthesis line was developed integrating different common reaction steps namely nitration, substitution and hydrogenation. Mesalazine as model drug substance was produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PAT strategy was implemented to equip the...
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A Continuous Process for Manufacturing Apremilast. Part I: Process Development and Intensification by Utilizing Flow Chemistry Principles
24 Apr 2024 | Peer-reviewed journal | Contributor(s): Hsieh, Hsiao-Wu, Griffin, Daniel J., Ananthoji, Padmini, Avci, Nadide Hazal, Brown, Derek B., Ericson, Ari, Fostinis, James D., Irfan, Muhammad, Langille, Neil, Lovette, Michael A., Murray, James I., Spada, Simone, Thiel, Oliver R., Aiello, Frankie, Daou, Joseph, Goudas-Salomon, Nicole, Pan, Ende, Sarkar, Nandini, Wimalasinghe, Rasangi, Wu, Zufan Steven, Zeng, Alicia, Beaver, Matthew G., Cohen, Carolyn M.
Herein, we report the development of an integrated continuous manufacturing (CM) process for the penultimate step in the synthesis of apremilast, the drug substance (DS) of the commercial product Otezla. This development effort was motivated by the desire to create an alternative manufacturing...
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Vendor Case Study: Twin Screw Extrusion For Continuous Manufacturing
04 Oct 2023 | Document | Contributor(s): Steve Post
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Videometric mass flow control: A new method for real-time measurement and feedback control of powder micro-feeding based on image analysis
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Madarasz, L, Kote, AGyurkes, M, Farkas, A, Hambalko, B, Pataki, H, Fulop, G, Marosi, G, Lengyel, L, Casian, T, Csorba, K, Nagy, ZK
The present paper reports the first monitoring and control of ultra-low dose powder feeding using a camera image-based mass flow measurement system. Caffeine was fed via a single-screw microfeeder as a model active pharmaceutical ingredient (API). The mass, mass flow and sizes of the particles...
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Using online mass spectrometry to predict the end point during drying of pharmaceutical products
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.
Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...
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Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing
09 Jun 2023 | Peer-reviewed journal | 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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Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi
While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...
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Twin-screw melt granulation: Current progress and challenges
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kittikunakorn, Nada, Liu, Tongzhou, Zhang, Feng
Twin-screw melt granulation (TSMG) is a new alternative method for granulation that offers several advantages over wet and dry granulation methods. TSMG has rapidly gained interest over recent years in the pharmaceutical industry. Since it is an inherently continuous process with controlled...
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Twin screw granulation - review of current progress
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Thompson, M. R.
Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of Research Article has...
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Towards a novel continuous HME-Tableting line: Process development and control concept
09 Jun 2023 | Peer-reviewed journal | 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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Towards 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients
09 Jun 2023 | Peer-reviewed journal | 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 Greener Pharmacy by More Eco Design
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Baron, M
This review proposes an overview of the main trends explored by the pharmaceutical industry in order to develop a greener and smarter pharmacy minimizing any negative impact to the environment, and using more sustainable processes and drugs. If many drugs have their origin in nature, many active...
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The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process
09 Jun 2023 | Peer-reviewed journal | 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 reality of in-line tablet coating
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cahyadi, Christine, Chan, Lai Wah, Heng, Paul Wan Sia
The possibility of continuous processing in pharmaceutical tablet manufacturing is hampered by the viscoelastic recovery of tablets post-compaction. Compacted tablets are typically aged before coating to allow complete viscoelastic recovery so as to avoid subsequent coating defects. There has...
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The Evolving State of Continuous Processing in Pharmaceutical API Manufacturing: A Survey of Pharmaceutical Companies and Contract Manufacturing Organizations
09 Jun 2023 | Peer-reviewed journal | Contributor(s): McWilliams, JC, Allian, ADOpalka, SM, May, SA, Journet, M, Braden, TM
This manuscript provides the results of an in-depth survey assessment of the capabilities, experience, and perspectives on continuous processing in the pharmaceutical sector, with respondents from both pharmaceutical companies and Contract Manufacturing Organizations (CMOs). The survey includes...
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The Future of Pharmaceutical Manufacturing Sciences
09 Jun 2023 | Peer-reviewed journal | 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 Future of Pharmaceutical Manufacturing Sciences
09 Jun 2023 | Peer-reviewed journal | 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...