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Development of a Continuous Flow Grignard Reaction to Manufacture a Key Intermediate of Ipatasertib
25 Jun 2024 | Contributor(s):: Kaldre, Dainis, Stocker, Severin, Linder, David, Reymond, Helena, Schuster, Andreas, Lamerz, Jens, Hildbrand, Stefan, Püntener, Kurt, Berry, Malcolm, Sedelmeier, Jörg
This article outlines the development of a continuous flow process for the manufacture of a key intermediate of the active pharmaceutical ingredient ipatasertib for the treatment of metastatic castration-resistant prostate cancer and triple-negative metastatic breast cancer. The reaction sequence...
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The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing
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 Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing
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
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 Current Scientific and Regulatory Landscape in Advancing Integrated Continuous Biopharmaceutical Manufacturing
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
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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Supervisory Control System for Monitoring a Pharmaceutical Hot Melt Extrusion Process
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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Spectroscopic characterization of tablet properties in a continuous powder blending and tableting process
09 Jun 2023 | Contributor(s):: Nagy, Brigitta, Farkas, Attila, Magyar, Krisztina, Démuth, Balázs, Marosi, György
By the advent of continuous pharmaceutical manufacturing, fast and accurate characterization of product quality has become of a major interest. Although it also promotes the real-time release testing approach, so far mainly content uniformity studies were performed by near-infrared (NIR)...
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Spray granulation for drug formulation
09 Jun 2023 | Contributor(s):: Loh, Zhi Hui, Er, Dawn Z. L., Chan, Lai Wah, Liew, Celine V., Heng, Paul W. S.
Introduction: Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration...
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Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and sustainable Fine-Chemical Manufacturing
09 Jun 2023 | Contributor(s):: Morin, Mathieu, Zhang, Wenyao, Mallik, Debasis, Organ, Michael G
Process analytical technology (PAT) is a system designed to help chemists better understand and control manufacturing processes. PAT systems operate through the combination of analytical devices, reactor control elements, and mathematical models to ensure the quality of the final product through...
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Risk Considerations on Developing a Continuous Crystallization System for Carbamazepine
09 Jun 2023 | Contributor(s):: Yang, Xiaochuan, Acevedo, David, Mohammad, Adil, Pavurala, Naresh, Wu, Huiquan, Brayton, Alex L., Shaw, Ryan A., Goldman, Mark J., He, Fan, Li, Shuaili, Fisher, Robert J., O'Connor, Thomas F., Cruz, Celia N.
Continuous manufacturing (CM) is an emerging technology in the pharmaceutical manufacturing sector, and the understanding of the impact on product quality is currently evolving. As the final purification and isolation step, crystallization has a significant impact on the final physicochemical...
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Robustness of a continuous direct compression line against disturbances in feeding
09 Jun 2023 | 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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Recent progress in continuous manufacturing of oral solid dosage forms
09 Jun 2023 | 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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Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing
09 Jun 2023 | 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
09 Jun 2023 | 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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Process analytical technology for continuous manufacturing tableting processing: A case study
09 Jun 2023 | 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 Tools for Monitoring Pharmaceutical Unit operations: A Control Strategy for Continuous Process Verification
09 Jun 2023 | Contributor(s):: Kim, Eun, Kim, Ji, Kim, Min-Soo, Jeong, Seong, Choi, Du
Various frameworks and methods, such as quality by design (QbD), real time release test (RTRT), and continuous process verification (CPV), have been introduced to improve drug product quality in the pharmaceutical industry. The methods recognize that an appropriate combination of process controls...
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Process Analytical Technology for Crystallization of Active Pharmaceutical Ingredients
09 Jun 2023 | 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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Pharmaceutical manufacturing and the quality by design (QBD), process analytical technology (PAT) approach
09 Jun 2023 | Contributor(s):: Murphy, Trevor, O’ Mahony, Niall, Panduru, Krishna, Riordan, Daniel, Walsh, Joseph
This paper is the result of a literature review focusing on the application of process analytical technology (PAT) for the pharmaceutical industry in conjunction with the quality by design (QBD) framework. PAT and the QBD framework put forward by the FDA, offer a holistic approach to...
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Pharmaceutical cocrystallization techniques. Advances and challenges
09 Jun 2023 | Contributor(s):: Rodrigues, M, Baptista, BLopes, JA, Sarraguca, MC
Cocrystals are homogenous (single-phase) crystalline structures composed by two or more components in a definite stoichiometric ratio bonded together by noncovalent bonds. Pharmaceutical industry has been showing interest in cocrystals due to their ability to improve active pharmaceutical...
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On-line monitoring of blend uniformity in continuous drug product manufacturing process -The impact of powder flow rate and the choice of spectrometer: Dispersive vs. FT
09 Jun 2023 | Contributor(s):: Shi, Zhenqi, McGhehey, Kathryn C, Leavesley, Ian M., Manley, Leo F.
One of the commonly acknowledged issues in continuous manufacturing of drug products is how to provide a representative sampling on flowing powder to assure its blend uniformity. An investigation was conducted to improve understanding on the impact of powder flow rate under different continuous...
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Opportunities for Process Control and Quality Assurance Using Online NIR Analysis to a Continuous Wet Granulation Tableting Line
09 Jun 2023 | Contributor(s):: Palmer J., O’Malley C.J., Wade M.J., Martin E.B., Page T., Montague G.A.
This paper investigates the application of online near-infrared measurements as a means to measure blend uniformity in a continuous tableting line. Underlying all the monitoring and control methods is the ability to measure key tablet properties online at a rate suitable for control purposes. The...
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Oscillatory Flow Reactors (OFRs) for Continuous Manufacturing and Crystallization
09 Jun 2023 | Contributor(s):: McGlone, Thomas, Briggs, Naomi E. B., Clark, Catriona A., Brown, Cameron J., Sefcik, Jan, Florence, Alastair J.
Continuous crystallization is an attractive approach for the delivery of consistent particles with specified critical quality attributes (CQAs), which are attracting increased interest for the manufacture of high value materials, including fine chemicals and pharmaceuticals. Oscillatory flow...
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Novel Impinging Jet and Continuous Crystallizer Design for Rapid Reactive Crystallization of Pharmaceuticals
09 Jun 2023 | Contributor(s):: Liu, WJ, Ma, CY, Wang, XZ
Reactive crystallization is an important operation in the pharmaceutical industry for the production of the active pharmaceutical ingredients (APIs), but has not been as widely studied as cooling or anti-solvent crystallization. Reactive crystallization has many unique features that make them...
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Near-infrared Spectroscopy for the In-line Characterization of Powder Voiding Part I: Development of the Methodology
09 Jun 2023 | Contributor(s):: Ropero, Jorge, Beach, Lauren, Alcala, Manel, Rentas, Raizza, Dave, Rajesh N., Romanach, Rodolfo J.
In-line near-infrared spectroscopy (NIR) spectra were acquired and analyzed to assess the relationship between physical and chemical properties of voiding powders and their spectral changes. NIR spectra were obtained for powders voiding from a conical glass funnel while the powder flow was...