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Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 1. Calibration workflow
24 Oct 2024 | Peer-reviewed journal | Contributor(s): Peter Toson, Marko Matić, Theresa Hörmann-Kincses, Michela Beretta, Jakob Rehrl, Johannes Poms, Thomas O’Connor, Abdollah Koolivand, Geng Tian, Scott M. Krull, Johannes G. Khinast, Dalibor Jajcevic, Johan Remmelgas
In this work, a high-fidelity digital twin was developed to support the design and testing of control strategies for drug product manufacturing via direct compression. The high-fidelity digital twin platform was based on typical pharmaceutical equipment, materials, and direct compression...
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Continuous Processing. Continuous Evolution
08 Oct 2024 | Magazine | Contributor(s): Douglas Hausner
Continuous processing for small molecule products has been a hot topic for years, but where does the industry stand with it today? We speak with Doug Hausner, Senior Manager, Continuous Manufacturing, Oral Solid Dose, Pharma Services at Thermo Fisher Scientific, to find out.
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Continuous micro feeding and mixing of solid dosage forms under vibrational excitation
08 Oct 2024 | Peer-reviewed journal | Contributor(s): Haifeng Lu, Liang Zhang, Hui Du, Xiaolei Guo, Haifeng Liu
Continuous manufacturing has intrigued many researchers in the pharmaceutical industry in the post-COVID-19 world. We experimentally studied the discharge characteristics of pharmaceutical excipients under vibrational excitation. The successful accurate dosing and filling of powders at fill...
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Systematic investigation of the impact of screw elements in continuous wet granulation
10 Sep 2024 | Peer-reviewed journal | Contributor(s): Katharina Kiricenko, Peter Kleinebudde, Robin Meier
Twin-screw wet granulation (TSG) is a continuous manufacturing technique either for granules as final dosage form or as an intermediate before tableting or capsule filling. A comprehensive process understanding is required to implement TSG, considering various parameters influencing granule and...
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Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing
13 Aug 2024 | Peer-reviewed journal | 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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Process intensification of pharmaceutical powder blending at commercial throughputs by utilizing semi-continuous mini-blending
13 Aug 2024 | Peer-reviewed journal | Contributor(s): Maarten Jaspers, Florian Tegel, Timo P. Roelofs, Fabian Starsich, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff
Process intensification involves the miniaturization of equipment while retaining process throughput and performance. The pharmaceutical industry can benefit from this approach especially during drug product development, where the availability of active pharmaceutical ingredients (API) is often...
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Improvement of a pharmaceutical powder mixing process in a tote blender via DEM simulations
04 Jun 2024 | Peer-reviewed journal | Contributor(s): Benedict Benque, Luca Orefice, Thomas Forgber, Matthias Habeler, Beate Schmid, Johan Remmelgas, Johannes Khinast
An industrial-scale pharmaceutical powder blending process was studied via discrete element method (DEM) simulations. A DEM model of two active pharmaceutical ingredient (API) components and a combined excipient component was calibrated by matching the simulated response in a dynamic angle of...
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A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction
03 Jun 2024 | Peer-reviewed journal | Contributor(s): Hikaru G. Jolliffe, Martin Prostredny, Carlota Mendez Torrecillas, Ecaterina Bordos, Collette Tierney, Ebenezer Ojo, Richard Elkes, Gavin Reynolds, Yunfei Li Song, Bernhard Meir, Sara Fathollahi, John Robertson
Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body...
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Influence of refilling on dosing accuracy of loss-in-weight powder feeders in continuous manufacturing
19 Feb 2024 | Peer-reviewed journal | Contributor(s): Jochen Thies, Peter Kleinebudde, Fabiola N. Santamaría Alvarez
Continuous manufacturing is a novel concept to produce high quality drug products. The manufacture of solid dosage forms starts with the feeding of materials, which is consider a critical step because it could have a high influence on the quality of the final product. Therefore, this unit...
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MOOC I Blending - Flow and Mixing Regime
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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MOOC I Feeding - Refill Strategy
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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MOOC I Blending Basics
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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MOOC I Continuous Blender Types
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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MOOC I Feeding - Twin Screw Feeder
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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MOOC I Feeding - Disturbances
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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MOOC I Continuous Blend Analysis
29 Nov 2023 | Teaching Materials | Contributor(s): RCPE
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Pharmaceutical Continuous Manufacturing: A Guide to Control Strategies for Solid Oral Dose Drugs
23 Aug 2023 | Technical Guides | Contributor(s): Atul Dubey
Advanced manufacturing technologies like pharmaceutical continuous manufacturing (PCM) can provide potential efficiencies for many medicines and their ingredients, thereby facilitating geographic diversity in manufacturing and supply chain resilience. One of the ways the U.S. Pharmacopeia (USP)...
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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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Wet Granulation in a Twin-Screw Extruder: Implications of Screw Design
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Thompson, M. R., Sun, J.
Wet granulation in twin-screw extrusion machinery is an attractive technology for the continuous processing of pharmaceuticals. The performance of this machinery is integrally tied to its screw design yet little fundamental knowledge exists in this emerging field for granulation to intelligently...
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WHAT are sampling errors-and WHAT can we do about them? Part 1
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Romañach, Rodolfo J., Joubert Castro, Aidalu, Esbensen, Kim H
The objective of this column is to provide easy-to-understand examples of sampling errors. Prompted by recent participationsand presentations at on-line conferences and meetings, we believe there is a need for a more fulfilling introduction andexemplification of the concept and real-world...
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Variographic analysis: A new methodology for quality assurance of pharmaceutical blending processes
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sánchez-Paternina, Adriluz, Sierra-Vega, Nobel O., Cárdenas, Vanessa, Méndez, Rafael, Esbensen, Kim H., Romañach, Rodolfo J.
Analytical methods for real time monitoring of pharmaceutical blending processes are thoroughly validated but not the sampling methods. Variographic analysis was investigated as a method to determine the sampling and analytical errors when the drug concentration of pharmaceutical powder blends is...
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Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vercruysse, Jurgen, Toiviainen, Maunu, Fonteyne, Margot, Helkimo, Niko, Ketolainen, Jarkko, Juuti, Mikko, Delaet, Urbain, Van Assche, Ivo, Remon, Jean Paul, Vervaet, Chris, De Beer, Thomas
Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw...
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Using a material property library to find surrogate materials for pharmaceutical process development
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Escotet-Espinoza, MS, Moghtadernejad, SScicolone, J, Wang, YF, Pereira, G, Schafer, E, Vigh, T, Klingeleers, D, Ierapetritou, M, Muzzio, FJ
Material properties are known to have a significant impact on pharmaceutical manufacturing performance, particularly for solid product processes. Evaluating the performance of a specific material, for example an active pharmaceutical ingredient or excipient, is critical during development stages...
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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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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,...