The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration

23 Jul 2024 | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.

Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

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 | 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...

Using a material property library to find surrogate materials for pharmaceutical process development

09 Jun 2023 | 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...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | 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,...

Using online mass spectrometry to predict the end point during drying of pharmaceutical products

09 Jun 2023 | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.

Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...

Using online mass spectrometry to predict the end point during drying of pharmaceutical products

09 Jun 2023 | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.

Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | 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,...

Understanding API Static Drying with Hot Gas Flow: Design and Test of a Drying Rig Prototype and Drying Modeling Development

09 Jun 2023 | Contributor(s): Ottoboni, S, Coleman, SJSteven, C, Siddique, M, Fraissinet, M, Joannes, M, Laux, A, Barton, A, Firth, P, Price, CJ, Mulheran, PA

Developing a continuous isolation process to produce a pure, dry, free-flowing active pharmaceutical ingredient (API) is the final barrier to the implementation of continuous end-to-end pharmaceutical manufacturing. Recent work has led to the development of continuous filtration and washing...

Towards a novel continuous HME-Tableting line: Process development and control concept

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...

Thin-Film Evaporator Model for Continuous Active Pharmaceutical Ingredient Manufacturing

09 Jun 2023 | Contributor(s): Lee, BW, Yin, KHSplaine, K, Roesch, B

Thin-film evaporator (TFE) is a popular continuous distillation/evaporation technology for pharmaceutical and fine chemical industries and has several equipment and process configurations that make fundamental modeling approaches very challenging. Specifically, moving wipers and lack of fluid...

The scope of PAT in real-time advanced control of tablet quality

09 Jun 2023 | Contributor(s): Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

Continuous pharmaceutical manufacturing together with process analytical technology (PAT) provides a suitable platform for automatic feed-forward/feed-back (FF/FB) control of the end product quality as desired by quality by design (QbD)-based efficient manufacturing. The precise control of the...

The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

The Changing Face of Process Development & Chemical Manufacturing - A View from the Regulators on Continuous Manufacturing

09 Jun 2023 | Contributor(s): Wiles, Charolotte

Industry wide there is a drive for resource efficiency and flexibility, to adapt quickly in what is increasingly becoming a volatile, changing marketplace. As the ‘patent cliff’ looms for many high-volume API’s, there is also a shift away from blockbusters towards lower volume, higher potency...

Technoeconomic Optimization of Continuous Crystallization for Three Active Pharmaceutical Ingredients: Cyclosporine, Paracetamol, and Aliskiren

09 Jun 2023 | Contributor(s): Diab, S, Gerogiorgis, DI

Mixed suspension, mixed product removal (MSMPR) crystallizers are widely implemented for the continuous crystallization of active pharmaceutical ingredients (APIs), allowing enhanced efficiency, flexibility, and product quality compared to currently dominant batch crystallizer designs....

Technoeconomic Optimization of a Conceptual Flowsheet for Continuous Separation of an Analgaesic Active Pharmaceutical Ingredient (API)

09 Jun 2023 | Contributor(s): Jolliffe, HG, Gerogiorgis, DI

Continuous Pharmaceutical Manufacturing (CPM) has recently emerged as a promising alternative to current batch production methods, which require significant expenditures in order to ensure product quality and process reliability. Advances in new continuous synthesis routes, demonstrations of full...

Systematic Framework for Design and Adaption of Fast, Flexible, Continuous Modular Plants

09 Jun 2023 | Contributor(s): Singh, Ravendra, Gernaey, Krist Gani, Rafiqul, Woodley, John

Not available

System-wide hybrid MPC–PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction

09 Jun 2023 | Contributor(s): Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

The next generation of QbD based pharmaceutical products will be manufactured through continuous processing. This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables,...

Systematic framework for implementation of material traceability into continuous pharmaceutical tablet manufacturing process

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...

Systematic substrate adoption methodology (SAM) for future flexible, generic pharmaceutical production processes

09 Jun 2023 | Contributor(s): Singh, Ravendra, Godfrey, Andy Gregertsen, Björn Muller, Frans Gernaey, Krist V Gani, Rafiqul, Woodley, John M

The discovery of an effective and safe pharmaceutical product is based on success in clinical trials. Often, several candidate compounds targeting the same disease area are tested in order to identify the most efficacious products. This involves the manufacture of small quantities of compounds...

System-wide hybrid MPC–PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction

09 Jun 2023 | Contributor(s): Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

The next generation of QbD based pharmaceutical products will be manufactured through continuous processing. This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables,...

Systematic computer-aided method and tool (ICAS-PAT) for design, analysis &/or validation of process monitoring and analysis systems (PAT systems)

09 Jun 2023 | Contributor(s): Singh, Ravendra, Gernaey, Krist, Gani, Rafiqul

Not available

Surrogate-based Optimization for Pharmaceutical Manufacturing Processes

09 Jun 2023 | Contributor(s): Wang, Zilong, Escotet-Espinoza, M Sebastian Singh, Ravendra, Ierapetritou, Marianthi

The development of pharmaceutical manufacturing processes has been facilitated by recent advances in the process simulation area. However, since the simulations are usually complex and the analytical expressions of the model can be unknown, it is difficult to directly apply traditional...

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...

Solvothermal Crystallization Kinetics and Control of Crystal Size Distribution of MOF-808 in a Continuous Flow Reactor

09 Jun 2023 | Contributor(s): Bagi, Sujay D., Myerson, Allan S. Román-Leshkov, Yuriy, Román-Leshkov, Yuriy

A fundamental understanding of the crystallization pathways for metal-organic frameworks (MOFs) allows for exploring the untapped combinatorial space of the organic and inorganic building units, creating possibilities to synthesize highly crystalline frameworks with desired physicochemical...