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Process Development for Synthesizing the Cephalosporin Antibiotic Cefotaxime in Batch and Flow Mode
24 Apr 2024 | Contributor(s):: Pieper, Matthias, Kumpert, Mario, König, Burghard, Schleich, Herbert, Bayer, Thomas, Gröger, Harald
The pharmaceutically active substance cefotaxime, a commercial cephalosporin-type antibiotic, is accessible in an amide-bond-forming reaction from 7-aminocephalosporanic acid as the amine donor and nonactivated (Z)-(2-aminothiazol-4-yl)-methoxyiminoacetic acid as the acid component with...
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Multi-step Flow Synthesis of the Anthelmintic Drug Praziquantel
24 Apr 2024 | 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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Technoeconomic optimisation and comparative environmental impact evaluation of continuous crystallisation and antisolvent selection for artemisinin recovery
09 Jun 2023 | Contributor(s):: Jolliffe, HG, Gerogiorgis, DI
Systematic nonlinear optimisation is a valuable tool towards evaluating the performance of conceptual Continuous Pharmaceutical Manufacturing (CPM) flowsheets. This study considers total cost minimisation of multiple plausible design choices and eight candidate antisolvents for the continuous...
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Surrogate-based Optimization for Pharmaceutical Manufacturing Processes
09 Jun 2023 | Contributor(s):: Wang, Zilong, Escotet-Espinoza, M Sebastian Singh, Ravendra, Ierapetritou, Marianthi
The development of pharmaceutical manufacturing processes has been facilitated by recent advances in the process simulation area. However, since the simulations are usually complex and the analytical expressions of the model can be unknown, it is difficult to directly apply traditional...
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Process Design and Optimization for the Continuous Manufacturing of Nevirapine, an Active Pharmaceutical Ingredient for HIV Treatment
09 Jun 2023 | Contributor(s):: Diab, S, McQuade, DTGupton, BF, Gerogiorgis, DI
The development of efficient and cost-effective manufacturing routes toward HIV active pharmaceutical ingredients (APIs) is essential to ensure their global and affordable access. Continuous pharmaceutical manufacturing (CPM) is a new production paradigm for the pharmaceutical industry whose...
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PharmaPy: An object-oriented tool for the development of hybrid pharmaceutical flowsheets
09 Jun 2023 | Contributor(s):: Casas-Orozco, Daniel, Laky, Daniel Wang, Vivian Abdi, Mesfin, Feng, X., Wood, E., Laird, Carl, Reklaitis, Gintaras V., Nagy, Zoltan K.
Process design and optimization continue to provide computational challenges as the chemical engineering and process optimization communities seek to address more complex and larger scale applications. Software tools for digital design and flowsheet simulation are readily available for...
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Perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes
09 Jun 2023 | Contributor(s):: Yang, WH, Qian, WXYuan, ZH, Chen, BZ
Pharmaceutical continuous manufacturing, especially under the context of COVID-19 pandemic, is regarded as an emerging technology that can guarantee the adequate quality assurance and mitigate process risk while guaranteeing the desirable economic performance. Flexibility analysis is one approach...
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Optimal Dynamic Continuous Manufacturing of Pharmaceuticals with Recycle
09 Jun 2023 | Contributor(s):: Patrascu, Michael, Barton, Paul I.
Continuous manufacturing of pharmaceuticals is challenged by short campaigns due to the low volume of some products. This calls for optimization of the entire dynamic campaign to achieve the highest overall yields and productivity and to minimize waste. In this paper, we investigate how recycles...
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Model-Based Systematic Design and Analysis Approach for Unseeded Combined Cooling and Antisolvent Crystallization (CCAC) Systems
09 Jun 2023 | Contributor(s):: Yang, Yang, Nagy, Zoltan K.
A novel model-based systematic analysis and design approach for unseeded combined cooling and antisolvent crystallization (CCAC) processes has been proposed and evaluated for the crystallization of aspirin in ethanol–water mixture. The approach can be easily implemented in practice using...
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Incorporating Solvent-Dependent Kinetics To Design a Multistage, Continuous, Combined Cooling/Antisolvent Crystallization Process
09 Jun 2023 | Contributor(s):: Schall, JM, Capellades, GMandur, JS, Braatz, RD, Myerson, AS
Combined cooling and antisolvent crystallization enables crystallization of many pharmaceutical products, but its process design typically neglects solvent composition influences on crystallization kinetics. This paper evaluates the influence of solvent-dependent nucleation and growth kinetics on...
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Flow chemistryMicroreaction technology comes of age
09 Jun 2023 | Contributor(s):: Jensen, KF
Over the past two decades, microreaction technology has matured from early devices and concepts to encompass a wide range of commercial equipment and applications. This evolution has been aided by the confluence of microreactor development and adoption of continuous flow technology in organic...
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Exploring the Role of Anti-solvent Effects during Washing on Active Pharmaceutical Ingredient Purity
09 Jun 2023 | Contributor(s):: Shahid, M, Sanxaridou, GOttoboni, S, Lue, L, Price, C
Washing is a key step in pharmaceutical isolation to remove the unwanted crystallization solvent (mother liquor) from the active pharmaceutical ingredient (API) filter cake. This study looks at strategies for optimal wash solvent selection, which minimizes the dissolution of API product crystals...
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Feedback in Flow for Accelerated Reaction Development
09 Jun 2023 | Contributor(s):: Reizman, BJ, Jensen, KF
The pharmaceutical industry is investing in continuous flow and high-throughput experimentation as tools for rapid process development accelerated scale-up. Coupled with automation, these technologies offer the potential for comprehensive reaction characterization and optimization, but with the...
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Estimation of Mass-Based Composition in Powder Mixtures Using Extended Iterative Optimization Technology (EIOT)
09 Jun 2023 | Contributor(s):: Shi, Zhenqi, Hermiller, James, García Muñoz, Salvador
The Extended Iterative Optimization Technology (EIOT) method is proposed as an extension to Muteki’s [I&ECR 2013;52 (35):12258–12268] Iterative Optimization Technology to address deviations from Beer–Lambert’s law in powders. The new method estimates the apparent spectrum for the pure species,...
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Dynamic flowsheet model development and digital design of continuous pharmaceutical manufacturing with dissolution modeling of the final product
09 Jun 2023 | Contributor(s):: Nagy, Brigitta, Szilágyi, Botond Domokos, András Vészi, Blanka, Tacsi, Kornélia, Rapi, Zsolt, Pataki, Hajnalka, Marosi, György, Nagy, Zoltán K., Nagy, Zsombor Kristóf
The integration of continuous unit operations imposes a challenge on the pharmaceutical companies aspiring to achieve plant-wide continuous manufacturing due to the additional complexity of the dynamic interactions, process control and quality assurance. To overcome this challenge, flowsheet...
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Development of a Novel Continuous Filtration Unit for Pharmaceutical Process Development and Manufacturing
09 Jun 2023 | Contributor(s):: Ottoboni, S, Price, CJSteven, C, Meehan, E, Barton, A, Firth, P, Mitchell, A, Tahir, F
The lack of a commercial laboratory, pilot and small manufacturing scale dead end continuous filtration and drying unit it is a significant gap in the development of continuous pharmaceutical manufacturing processes for new active pharmaceutical ingredients (APIs). To move small-scale...
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Developing a Batch Isolation Procedure and Running It in an Automated Semicontinuous Unit: AWL CFD25 Case Study
09 Jun 2023 | Contributor(s):: Ottoboni, S, Shahid, MSteven, C, Coleman, S, Meehan, E, Barton, A, Firth, P, Sutherland, R, Price, CJ
A key challenge during the transition from laboratory/small batch to continuous manufacturing is the development of a process strategy that can easily be adopted for a larger batch/continuous process. Industrial practice is to develop the isolation strategy for a new drug/process in batch using...
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Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate
09 Jun 2023 | Contributor(s):: Christensen, KM, Pedersen, MJDam-Johansen, K, Holm, TL, Skovby, T, Kiil, S
A novel filter reactor system for continuous production of selected pharmaceutical intermediates is presented and experimentally verified. The filter reactor system consists of a mixed flow reactor equipped with a bottom filter, to retain solid reactant particles, followed by a conventional plug...
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A systematic reactor design approach for the synthesis of active pharmaceutical ingredients
09 Jun 2023 | Contributor(s):: Emenike, VN, Schenkendorf, R, Krewer, U
Today's highly competitive pharmaceutical industry is in dire need of an accelerated transition from the drug development phase to the drug production phase. At the heart of this transition are chemical reactors that facilitate the synthesis of active pharmaceutical ingredients (APIs) and whose...
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A novel robust digital design of a network of industrial continuous cooling crystallizers of dextrose monohydrate: From laboratory experiments to industrial application
09 Jun 2023 | Contributor(s):: Nagy, Zoltan K., Szilagyi, Botond Pal, Kanjakha, Tabar, Iman Beheshti ;
This paper presents the first-ever industrial application of the digital design of a complex, large-scale industrial continuous crystallization network. The aim of the work is to optimize a large-scale continuous crystallization network used for the purification of dextrose monohydrate, by...