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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
Peer-reviewed journal | 24 Oct 2024 | 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 micro feeding and mixing of solid dosage forms under vibrational excitation
Peer-reviewed journal | 08 Oct 2024 | 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
Peer-reviewed journal | 10 Sep 2024 | 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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Improvement of a pharmaceutical powder mixing process in a tote blender via DEM simulations
Peer-reviewed journal | 04 Jun 2024 | 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
Peer-reviewed journal | 03 Jun 2024 | 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
Peer-reviewed journal | 19 Feb 2024 | 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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Variographic analysis: A new methodology for quality assurance of pharmaceutical blending processes
Peer-reviewed journal | 09 Jun 2023 | 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
Peer-reviewed journal | 09 Jun 2023 | 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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Wet Granulation in a Twin-Screw Extruder: Implications of Screw Design
Peer-reviewed journal | 09 Jun 2023 | 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
Peer-reviewed journal | 09 Jun 2023 | 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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Use of a continuous twin screw granulation and drying system during formulation development and process optimization
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Vercruysse, J., Peeters, E., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.
Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are...
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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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Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing
Peer-reviewed journal | 09 Jun 2023 | 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,...
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Validation of a continuous granulation process using a twin-screw extruder
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Van Melkebeke, B., Vervaet, C., Remon, J. P.
Using twin-screw granulation as particle size enlargement technique, the effect of modifying the screw configuration (number of mixing zones, configuration of kneading block) on granule quality, tablet properties and mixing efficiency was investigated. The amount of oversized agglomerates and...
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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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Transfer from High-Shear Batch to Continuous Twin Screw Wet Granulation: A Case Study in Understanding the Relationship Between Process Parameters and Product Quality Attributes
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Beer, Paul, Wilson, David, Huang, Zhenyu, De Matas, Marcel
A twin screw to high-shear batch granulation technology switch was evaluated for a pharmaceutical development project. Differences in granule (particle size distribution and porosity) and tablet (dissolution) quality attributes were analysed for both continuous and batch technologies. Liquid to...
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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 granulation as a simple and efficient tool for continuous wet granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Keleb, EI, Vermeire, A, Vervaet, C, Remon, JP
The modification of a twin screw extruder for continuous wet granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw...
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Twin Screw Granulation: Effects of Properties of Primary Powders
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Lute, Sushma, V, Dhenge, Ranjit M., Salman, Agba D.
Lactose and mannitol are some of the most commonly used powders in the pharmaceutical industry. The limited Research Article published so far highlights the effects of process and formulation parameters on the properties of the granules and the tablets produced using these two types of powders...
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Twin-screw granulation and high-shear granulation: The influence of mannitol grade on granule and tablet properties
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Megarry, Andrew, Taylor, Agnes, Gholami, Aida, Wikstrom, Hakan, Tajarobi, Pirjo
Granule structure has a key influence on tablet critical quality attributes. The ability to control this structure through excipient choice is an important part of formulation development. Mannitol is a popular diluent and the choice of input grade has been shown to impact granule properties....
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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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The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Monteyne, Tinne, Heeze, Liza, Mortier, Severine Therese F. C., Oldoerp, Klaus, Cardinaels, Ruth, Nopens, Ingmar, Vervaet, Chris, Remon, Jean-Paul, De Beer, Thomas
Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of...
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The use of rheology to elucidate the granulation mechanisms of a miscible and immiscible system during continuous twin-screw melt granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Monteyne, Tinne, Heeze, Liza, Mortier, Severine Therese F. C., Oldorp, Klaus, Nopens, Ingmar, Remon, Jean-Paul, Vervaet, Chris, De Beer, Thomas
Twin-screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to granulate temperature and moisture sensitive drugs in a continuous way. Recently, the material behavior of an immiscible drug-binder blend during TS HMG was unraveled by using a rheometer and differential...
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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...