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Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing
Peer-reviewed journal | 13 Aug 2024 | Contributor(s):: Sara Fathollahi, Pauline H. M. Janssen, Bastiaan H. J. Dickhoff, Henderik W. Frijlink
The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of...
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Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant
Peer-reviewed journal | 09 Jul 2024 | 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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Implementation of a fully integrated continuous manufacturing line for direct compression and coating at a commercial pharmaceutical facility – Part 1: Operational considerations and control strategy
Peer-reviewed journal | 25 Jun 2024 | Contributor(s):: Conway, Stephen L., Rosas, Juan G., Overton, Paul, Tugby, Neil, Cryan, Phillip, Witulski, Frank, Hurley, Samantha, Wareham, Laura, Tantuccio, Anthony, Ramasamy, Manoharan, Lalloo, Anita, Gibbs, Mason, Meyer, Robert F.
We implement a fully integrated continuous manufacturing (CM) line for direct compression and coating of a pharmaceutical oral solid dosage form in a commercial production facility. In this first paper of a two-part series, we describe process design and operational choices made to introduce CM...
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Implementation of a fully integrated CM direct compression and coating process at a commercial pharmaceutical facility - Part 2: PAT and RTD results for normal operational conditions batches.
Peer-reviewed journal | 25 Jun 2024 | Contributor(s):: Rosas, JG, Brush, P, Thompson, B, Miller, C, Overton, P, Tugby, N, Stoliarskaia, D, Hurley, S, Ramasamy, M, Conway, SL
This is the second of two articles detailing the continuous manufacturing (CM) development and implementation activities for an marketed product which have been realized in novel, qualified equipment, using validated control strategy elements to enable manufacture of batches under current good...
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Lubricant Sensitivity of Direct Compression Grades of Lactose in Continuous and Batch Tableting Process
Peer-reviewed journal | 16 Nov 2023 | Contributor(s):: Gerald A. Hebbink, Pauline H. M. Janssen, Jurjen H. Kok, Lorenzo Menarini, Federica Giatti, Caterina Funaro, Salvatore Fabrizio Consoli, Bastiaan H. J. Dickhoff
Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and...
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A Comparative Investment Analysis of Batch Versus Continuous Pharmaceutical Manufacturing Technologies
Peer-reviewed journal | 04 Oct 2023 | Contributor(s):: Clifford V. Rossi
Purpose This study examines the risks and economics associated with investing in continuous (CM) versus conventional batch manufacturing for production of oral solid dosage pharmaceutical (OSD) products in the USA and abroad. Methods A stochastic net present value (NPV) simulation of brand...
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Effect of batch-to-batch variation of spray dried lactose on the performance of feeders
Peer-reviewed journal | 10 Aug 2023 | Contributor(s):: Carlota Mendez Torrecillas, Florian Tegel, Ralf Weinekötter, Bernhard Meir, Bastiaan H.J. Dickhoff, Sri Sharath Kulkarni, Pauline H.M. Janssen
With the emergence of quality by design (QbD), it becomes imperative to gain understanding of the impact of batch-to-batch variability of raw materials on the performance of processes. Feeding is the first unit of operation in a continuous manufacturing line and is critical for the final product...
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Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Clive Badman, Charles L.Cooney, Alastair Florence, Konstantin Konstantinov, Markus Krumme, Salvatore Mascia, Moheb Nasr, Bernhardt L. Trout
We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.
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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 the channel fill level in defining a design space for twin screw wet granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Gorringe, L. J., Kee, G. S., Saleh, M. F., Fa, N. H., Elkes, R. G.
Twin screw wet granulation is a key process in the continuous manufacture of oral solid dosage forms. Previous Research Article has qualitatively suggested that the channel fill level influences the granules produced. In this paper a quantitative measure of the total volumetric fraction of the...
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TPLS as predictive platform for twin-screw wet granulation process and formulation development
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Ryckaert, A., Van Hauwermeiren, D., Dhondt, J., De Man, A., Funke, A., Djuric, D., Vervaet, C., Nopens, I., De Beer, T.
In recent years, the interest in continuous manufacturing techniques, such as twin-screw wet granulation, has increased. However, the understanding of the influence of the combination of raw material properties and process settings upon the granule quality attributes is still limited. In this...
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Tracking raw material flow through a continuous direct compression line. Part II of II: Predicting dynamic changes in quality attributes of tablets due to disturbances in raw material properties using an independent residence time distribution model
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Peterwitz, M, Buchgeister, SMeier, R, Schembecker, G
Continuous manufacturing of pharmaceuticals promises many advantages regarding economics and quality. However, tracing deviating material in such processes is much more challenging than in batch processes due to axial back-mixing. The literature has proven the traceability of disturbances in the...
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Twin screw granulation - review of current progress
Peer-reviewed journal | 09 Jun 2023 | 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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Twin-screw melt granulation: Current progress and challenges
Peer-reviewed journal | 09 Jun 2023 | 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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Towards a Continuous Manufacturing Process of Protein-Loaded Polymeric Nanoparticle Powders
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Schiller, Stefan, Hanefeld, Andrea, Schneider, Marc, Lehr, Claus-Michael
To develop a scalable and efficient process suitable for the continuous manufacturing of poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing ovalbumin as the model protein. PLGA nanoparticles were prepared using a double emulsification spray-drying method. Emulsions were prepared using...
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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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Towards Continuous Primary Manufacturing Processes-Particle Design through Combined Crystallization and Particle Isolation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Steenweg, C, Kufner, ACHabicht, J, Wohlgemuth, K
Integrated continuous manufacturing processes of active pharmaceutical ingredients (API) provide key benefits concerning product quality control, scale-up capability, and a reduced time-to-market. Thereby, the crystallization step, which is used in approximately 90% of API productions, mainly...
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The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Ryckaert, Alexander, Ghijs, Michael, Portier, Christoph, Djuric, Dejan, Funke, Adrian, Vervaet, Chris, De Beer, Thomas
The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying...
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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 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 effect of screw configuration and formulation variables on liquid requirements and granule quality in a continuous twin screw wet granulation process
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Vandevivere, L., Van Wijmeersch, E., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.
The effect of two screw configurations with varying stagger angle was evaluated on the liquid amount required to produce good quality granules for a highly (mannitol-based) and a poorly (DCP-based) soluble formulation containing different binders. It is generally known that the use of a higher...
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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 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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Systematic framework for implementation of material traceability into continuous pharmaceutical tablet manufacturing process
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Billups, Matthew, Singh, Ravendra
Purpose: With the applications of more advanced manufacturing technologies being applied to the pharmaceutical industry, continuous processes are at the forefront of innovation. One area that is highly desired to be systematically investigated is material traceability in continuous manufacturing...
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Tablet Quality-Prediction Model Using Quality Material Attributes: Toward Flexible Switching Between Batch and Continuous Granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Arai, H, Nagato, TKoide, T, Yonemochi, E, Yamamoto, H, Sugiyama, H
Purpose The purpose of the study was to develop a model to predict the critical quality attribute (CQA) of tablets during continuous and batch manufacturing using only critical material attributes (CMAs). Methods Experiments were performed using ethenzamide as the active pharmaceutical ingredient...