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The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry
Contributor(s):: Baumann, M, Baxendale, IR
The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient...
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The Use of Molecular Oxygen in Pharmaceutical Manufacturing: Is Flow the Way to Go?
Contributor(s):: Hone, CA, Roberge, DM, Kappe, CO
Molecular oxygen is arguably the greenest reagent available to the organic chemist. Most commonly, a diluted form of oxygen gas, consisting of less than 10% O-2 in N-2 ("synthetic air"), is used in pharmaceutical and fine chemical batch manufacturing to effectively address safety concerns when...
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Recent advances in integrated process analytical techniques, modeling, and control strategies to enable continuous biomanufacturing of monoclonal antibodies
Contributor(s):: Chopda, Viki, Gyorgypal, Aron Yang, Ou Singh, Ravendra Ramachandran, Rohit Zhang, Haoran Tsilomelekis, George Chundawat, Shishir PS, Ierapetritou, Marianthi G
Continuous bioprocessing is significantly changing the biological drugs (or biologics) manufacturing landscape by potentially improving product quality, process stability, and overall profitability, as was similarly seen during the adoption of advanced manufacturing processes for small molecule...
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Reducing the mean size of API crystals by continuous manufacturing with product classification and recycle
Contributor(s):: Griffin, DW, Mellichamp, DA, Doherty, MF
A continuous crystallization process is proposed that can produce active pharmaceutical ingredients with a small mean size and narrow distribution. The process flowsheet consists of a new product classifier configuration where the large crystals from the classifier are recycled to a dissolver...
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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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Process Analytical Technology for Crystallization of Active Pharmaceutical Ingredients
Contributor(s):: Malwade, CR, Qu, HY
Background: Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities....
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Perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes
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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Perspectives on the continuous manufacturing of powder‐based pharmaceutical processes
Contributor(s):: Marianthi Ierapetritou, Fernando Muzzio, Gintaras Reklaitis
The Pharmaceutical industry is a global business sector with $1 trillion annual sales focused on performance based products designed to address the healthcare needs of the world's population. In the last decade, the industry has been experiencing a number of important changes in its business...
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Monitoring of the combined cooling and antisolvent crystallisation of mixtures of aminobenzoic acid isomers using ATR-UV/vis spectroscopy and FBRM
Contributor(s):: Saleemi, AN, Rielly, CD, Nagy, ZK
During the manufacturing of active pharmaceutical ingredients crystalline products in the purest forms are required. Quite often multiple components are present during crystallisation, which requires their continuous monitoring and finally separation. The current work demonstrates the application...
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Metabolic Engineering: The Ultimate Paradigm for Continuous Pharmaceutical Manufacturing
Contributor(s):: Yadav, VG, Stephanopoulos, G
Research Article and development (R&D) expenditures by pharmaceutical companies doubled over the past decade, yet candidate attrition rates and development times rose markedly during this period. Understandably, companies have begun downsizing their pipelines and diverting investments away from...
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Integrated Purification and Formulation of an Active Pharmaceutical Ingredient via Agitated Bed Crystallization and Fluidized Bed Processing
Contributor(s):: Stocker, MW, Harding, MJTodaro, V, Healy, AM, Ferguson, S
Integrated API and drug product processing enable molecules with high clinical efficacy but poor physicochemical characteristics to be commercialized by direct co-processing with excipients to produce advanced multicomponent intermediates. Furthermore, developing isolation-free frameworks would...
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Improving chemical synthesis using flow reactors
Contributor(s):: Wiles, C, Watts, P
Owing to the competitive nature of the pharmaceutical industry, Research Articleers involved in lead compound generation are under continued pressure to identify and develop promising programmes of Research Article in order to secure intellectual property. The potential of a compound for...
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Effects of processing parameters and blade patterns on continuous pharmaceutical powder mixing
Contributor(s):: Osorio, JG, Muzzio, FJ
The present study summarizes the experimental characterization of a new continuous powder mixer (GCG-70 by Glatt (R)) using common pharmaceutical ingredients. The powder hold-up and residence time distribution were used to characterize the bulk behavior of the mixer as a function of impeller...
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Development and applications of a material library for pharmaceutical continuous manufacturing of solid dosage forms
Contributor(s):: Yifan Wang, ThomasO'Connor, TianyiLi, Muhammad Ashraf
The purpose of this study is to establish a material library and discuss its potential application to the development and lifecycle management of a continuous manufacturing process for solid dosage forms. Particularly, this study addresses the importance of selecting process-relevant testing...
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Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate
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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Continuous-Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients
Contributor(s):: Gutmann, B, Cantillo, D, Kappe, CO
In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of...
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Continuous mixing of powder mixtures with pharmaceutical process constraints
Contributor(s):: Berthiaux, H, Marikh, K, Gatumel, C
While it would provide many advantages from many aspects, the application of continuous mixing processes to the pharmaceutical field is still in its infancy. In this paper we report results concerning the continuous mixing of nine ingredients (including three actives) that constitute a current...
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Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing
Contributor(s):: Burcham, Christopher L., Florence, Alastair J., Johnson, Martin D.
The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new...
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Application of Ultra-Performance Liquid Chromatography as an Online Process Analytical Technology Tool in Pharmaceutical Crystallization
Contributor(s):: Yang, Yang, Zhang, Chuntao Pal, Kanjakha Koswara, Andy, Quon, Justin, Mckeown, Rahn, Goss, Charles, Nagy, Zoltan K
Concentration is often an important process parameter in pharmaceutical crystallization processes. In this work, an ultra-performance liquid chromatography (UPLC) system designed for process monitoring (Waters PATROL UPLC) was applied online as a process analytical technology tool for real-time...