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Automated and continuous synthesis of drug substances
| Contributor(s):: Sacher, Stephan, Castillo, Ismael, Rehrl, Jakob, Sagmeister, Peter, Lebl, René, Kruisz, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D., Kirschneck, Dirk, Kappe, C. Oliver, Horn, Martin
A continuous synthesis line was developed integrating different common reaction steps namely nitration, substitution and hydrogenation. Mesalazine as model drug substance was produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PAT strategy was implemented to equip the...
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Vendor Case Study: Twin Screw Extrusion For Continuous Manufacturing
| Contributor(s):: Steve Post
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Addressing Barriers in Implementing Pharmaceutical Continuous Manufacturing Key Concepts & Challenges in Pharmaceutical Continuous Manufacturing
| Contributor(s):: Gabriela Grasa Mannino
Pharmaceutical continuous manufacturing (PCM) can reduce production time, decrease labor costs, and optimize process flow and the supply chain. Although some industry leaders have already invested in PCM, its widespread implementation has yet to be achieved. Major challenges to adoption include...
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Sarah George
https://cmkc.usp.org/members/1118
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Rohit Lokhande
I am a seasoned professional in the pharmaceutical industry with over 13 years of experience, specializing in the chemical synthesis of APIs and intermediates. My journey with the Chemistry world...
https://cmkc.usp.org/members/1109
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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
| 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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Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing
| 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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The Future of Pharmaceutical Manufacturing Sciences
| Contributor(s):: Rantanen, Jukka, Khinast Johannes
The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is...
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Roller compaction: Infrared thermography as a PAT for monitoring powder flow from feeding to compaction zone
| Contributor(s):: Yu, Mingzhe, Omar, Chalak, Weidemann, Marcus, Schmidt, Alexander, Litster, James D., Salman, Agba D.
Roller compaction is a continuous dry granulation process, in which powder is compressed by two counter-rotating rollers. During this process, the powder feeding to the compaction zone has a significant effect on product quality. This work investigates the flow of powder from the feeding zone to...
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Real-time feedback control of twin-screw wet granulation based on image analysis
| Contributor(s):: Madarasz, Lajos, Hoffer, Istvan, Szabo, Barnabas, Csontos, Istvan, Pataki, Hajnalka, Demuth, Balazs, Szabo, Bence, Csorba, Kristof, Nagy, Zsombor Kristof, Marosi, Gyorgy
The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored...
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Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process
| Contributor(s):: Huang, Yan-Shu, Medina-González, Sergio Straiton, Benjamin Keller, Joshua, Marashdeh, Qussai, Gonzalez, Marcial, Nagy, Zoltan, Reklaitis, Gintaras V.
While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the...
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Real-time process monitoring in a semi-continuous fluid-bed dryer - microwave resonance technology versus near-infrared spectroscopy
| Contributor(s):: Peters, Johanna, Teske, Andreas, Taute, Wolfgang, Döscher, Claas, Höft, Michael, Knöchel, Reinhard, Breitkreutz, Jörg
The trend towards continuous manufacturing in the pharmaceutical industry is associated with an increasing demand for advanced control strategies. It is a mandatory requirement to obtain reliable real-time information on critical quality attributes (CQA) during every process step as the decision...
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Raman Spectroscopy for Monitoring the Continuous Crystallization of Carbamazepine
| Contributor(s):: Acevedo, D, Mohammad, Adil, Pavurala, Naresh, Wu, Wei-Lee, O'Connor, Thomas F., Nagy, Zoltan K, Yang, Xiaochuan, Cruz, CN
Crystallization has a significant impact on the properties of the active pharmaceutical ingredient (API) since it is the final step in the manufacturing of the drug substance and determines particle size distribution, purity, shape, and polymorphs. Many publications have focused on the...
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Process analytical technology in continuous manufacturing of a commercial pharmaceutical product
| Contributor(s):: Vargas, Jenny, Nielsen, Sarah, Cárdenas, Vanessa, Gonzalez, Anthony, Aymat, Efrain, Almodovar, Elvin, Classe, Gustavo, Colón, Yleana, Sanchez, Eric, Romañach, Rodolfo
The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial...
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PAT for pharmaceutical manufacturing process involving solid dosages forms
| Contributor(s):: Román-Ospino, Andrés D, Cárdenas, Vanessa Ortega-Zuñiga, Carlos, Singh, Ravendra
This chapter summarizes important considerations to develop multivariate methods for pharmaceuticals process monitoring and quality control in solid dosages forms based on spectroscopic techniques. The stages described in each section aimed to explain relevant knowledge of the calibration...
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PAT Implementation on a Mobile Continuous Pharmaceutical Manufacturing System: Real-Time Process Monitoring with In-Line FTIR and Raman Spectroscopy
| Contributor(s):: Miyai, Yuma, Formosa, Anna, Armstrong, Cameron, Marquardt, Brian, Rogers,
Luke, Roper, Thomas
The strategies and experimental methods for implementation of process analytical technology (PAT) on the mobile pharmaceutical manufacturing system, Pharmacy on Demand (PoD), are discussed. With multiple processes to be monitored on the PoD end-to-end continuous manufacturing process, PAT and its...
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Near infrared spectroscopic calibration models for real time monitoring of powder density
| Contributor(s):: Román-Ospino, Andrés, Singh, Ravendra, Ierapetritoua, Marianthi, Ramachandrana, Rohit, Mendez, Rafael, Ortega-Zuñiga, Carlos, Muzzio, Fernando, Romañach, Rodolfo
Near infrared spectroscopic (NIRS) calibration models for real time prediction of powder density (tap, bulk and consolidated) were developed for a pharmaceutical formulation. Powder density is a critical property in the manufacturing of solid oral dosages, related to critical quality attributes...
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Near-infrared spectroscopic applications in pharmaceutical particle technology
| Contributor(s):: Razuc, M, Grafia, AGallo, L, Ramirez-Rigo, MV, Romanach, RJ
Near-infrared spectroscopy (NIRS) is nowadays an established analytical technique in the pharmaceutical industry. The aim of this review is to present the progress of NIRS in providing useful information for pharmaceutical particle technology. NIR methods are now developed to characterize a wide...
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Method transfer of a near-infrared spectroscopic method for blend uniformity in a poorly flowing and hygroscopic blend
| Contributor(s):: Alvarado-Hernández, Bárbara, Scicolone, James, Ortega-Zuñiga, Carlos, Román-Ospino, Andrés, Colón-Lugo, Yleana, Aymat, Efrain, Sánchez, Eric, Muzzio, Fernando, Romañach, Rodolfo
The challenges in transferring and executing a near-infrared (NIR) spectroscopic method for croscarmellose (disintegrant) in binary blends for a continuous manufacturing (CM) process are presented. This work demonstrates the development of a NIR calibration model and its use to determine the...
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In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development
| Contributor(s):: Madarász, Lajos, Köte, Ákos, Hambalkó, Bence, Csorba, Kristóf, Kovács, Viktor, Lengyel, László, Marosi, Györgya, Farkas, Attilaa, Nagy, Zsombor Kristóf, Domokos, András
The present paper serves as a demonstration how an in-line PAT tool can be used for rapid and efficient process development in a fully continuous powder to granule line consisting of an interconnected twin-screw wet granulator, vibrational fluid bed dryer, and a regranulating mill. A new method...
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In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process
| Contributor(s):: Nagy, Brigitta, Farkas, Attila, Gyurkes, Martin, Komaromy-Hiller, Szofia, Demuth, Balazs, Szabo, Bence, Nusser, David, Borbas, Eniko, Marosi, Gyorgy, Nagy, Zsombor Kristof
The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a...
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In-line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)
| Contributor(s):: Schlindwein, Walkiria, Bezerra, Mariana, Almeida, Juan, Berghaus, Andreas, Owen, Martin, Muirhead, Gordon
This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line...
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Inline monitoring and a PAT strategy for pharmaceutical hot-melt extrusion
| Contributor(s):: Wahl, PR, Treffer, DMohr, S, Roblegg, E, Koscher, G, Khinast, JG
Implementation of continuous manufacturing in the pharmaceutical industry requires tight process control. This study focuses on a PAT strategy for hot melt extrusion of vegetable calcium stearate (CaSt) as matrix carrier and paracetamol as active pharmaceutical ingredient (API). The extrusion was...
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How to measure coating thickness of tablets: Method comparison of optical coherence tomography, near-infrared spectroscopy and weight-, height- and diameter gain
| Contributor(s):: Wahl, P. R., Peter, A., Wolfgang, M., Khinast, J. G.
Film coating of pharmaceutical dosage forms, such as tablets and pellets, can be used to tailor the drug release profile. With that regard, a uniform coating thickness of a single tablet (intra-tablet), all tablets (inter-tablet) and subsequent batches (inter-batch) is crucial. We present a...
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Hot melt extrusion technology for continuous manufacturing
| Contributor(s):: Furqan Tahir, Lovett. David
Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, is now attracting significant interest from the pharmaceutical manufacturing sector. This is primarily because HME enables the continuous manufacture of a wide variety of dosage...