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Towards Continuous Primary Manufacturing Processes-Particle Design through Combined Crystallization and Particle Isolation
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
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 impact of channel fill level on internal forces during continuous twin screw wet granulation
Contributor(s):: Torrecillas, Carlota Mendez, Gorringe, Lee J., Rajoub, Nazer, Robertson, John, Elkes, Richard G., Lamprou, Dimitrios A., Halbert, Gavin W
The forces experienced by the particles inside a twin screw granulator (TSG) are one of the most difficult parameters to measure quantitatively. However, it is possible to perform accurately this measurement through the use of dye containing calibrated microencapsulated sensors (LAMES) whose...
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Seeded droplet microfluidic system for small molecule crystallization
Contributor(s):: Garg, N, Tona, RMartin, P, Martin-Soladana, PM, Ward, G, Douillet, N, Lai, D
A microfluidic approach to seeded crystallization has been demonstrated using abacavir hemisulfate, a nucleoside analog reverse transcriptase inhibitor, in droplet reactors to control polymorphism and produce particles with a low particle size distribution. Two techniques are introduced: (1) the...
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Regions of attainable particle sizes in continuous and batch crystallization processes
Contributor(s):: Vetter, Thomas, Burcham, Christopher L., Doherty, Michael F.
Process alternatives for continuous crystallization, i.e., cascades of mixed suspension, mixed product removal crystallizers (MSMPRCs) and plug flow crystallizers (PFCs), as well as batch crystallizers are discussed and modeled using population balance equations. The attainable region approach...
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Real-time monitoring of particle size distribution in a continuous granulation and drying process by near infrared spectroscopy
Contributor(s):: Pauli, V, Roggo, YKleinebudde, P, Krumme, M
In continuous granulation, it can be important to control granules particle size distribution (PSD), as it may affect final product quality. Near infrared spectroscopy (NIRS) is already a routine analytical procedure within pharmaceutical continuous manufacturing for the in-line analysis of...
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Influence of granulation temperature on particle size distribution of granules in twin-screw granulation (TSG)
Contributor(s):: Ito, Akihiko, Kleinebudde, Peter
This study investigated an influence of granulation temperature during twin-screw granulation (TSG) on particle size distributions (PSDs). The influence of the granulation temperature on granule size distributions varied, depending on the liquid to solid (L/S) ratio, the kind of binders, the...
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Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation
Contributor(s):: Vercruysse, J, Burggraeve, A., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.
Twin screw granulation (TSG) has been reported by different Research Article groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution...
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Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid-Liquid Separation of Suspensions
Contributor(s):: Steenweg, C, Seifert, AISchembecker, G, Wohlgemuth, K
A key enabler for the future success of continuous manufacturing in pharmaceutical and fine chemical production processes is the control of product quality. Since approx. 90% of all small molecular active pharmaceutical ingredients produced involve a crystallization step, a holistic view on its...
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Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer
Contributor(s):: De Leersnyder, F., Vanhoorne, V., Bekaert, H., Vercruysse, J., Ghijs, M., Bostijn, N., Verstraeten, M., Cappuyns, P., Van Assche, I., Vander Heyden, Y., Ziemons, E., Remon, J. P., Nopens, I., Vervaet, C., De Beer, T.
Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and,...
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API Continuous Cooling and Antisolvent Crystallization for Kinetic Impurity Rejection in cGMP Manufacturing
Contributor(s):: Johnson, MD, Burcham, CLMay, SA, Calvin, JR, Groh, JM, Myers, SS, Webster, LP, Roberts, JC, Reddy, VR, Luciani, CV, Corrigan, AP, Spencer, RD, Moylan, R, Boyse, R, Murphy, JD, Stout, JR
Crystallization of 204 kg of final active pharmaceutical ingredient was accomplished continuously using a cascade of mixed suspension mixed product removal crystallizers in cGMP manufacturing. This article describes the journey taken to transform a set of technical to final batch crystallizations...