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ICAS-PAT: A software for design, analysis and validation of PAT systems
Contributor(s):: Singh, Ravendra, Gernaey, Krist V, Gani, Rafiqul
In chemicals based product manufacturing, as in pharmaceutical, food and agrochemical industries, efficient and consistent process monitoring and analysis systems (PAT systems) have a very important role. These PAT systems ensure that the chemicals based product is manufactured with the specified...
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Impact of blend properties and process variables on the blending performance
Contributor(s):: Bekaert, B, Grymonpre, W, Novikova, A, Vervaet, C, Vanhoorne, V
In this study, quantitative relationships were established between blend properties, process settings and blending responses via multivariate data-analysis. Four divergent binary blends were composed in three different ratios and processed at various throughputs and impeller speeds. Additionally,...
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Guidance for Industry PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance
This guidance is intended to describe a regulatory framework (Process Analytical Technology, PAT) that will encourage the voluntary development and implementation of innovative pharmaceutical development, manufacturing, and quality assurance. Working with existing regulations, the Agency has...
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Holistic Control Strategies for Continuous Manufacturing
Contributor(s):: Moore, Christine, Garcia, Thomas, Hausner, Douglas B., Ben-Anat, Inna
Innovative technologies such as continuous manufacturing (CM) bring speed, efficiency, and agility to pharmaceutical manufacturing together with enhanced process robustness and assurance of product quality. During CM, material is simultaneously charged and discharged into process unit operations....
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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...
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Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation
Contributor(s):: Patil, H, Tiwari, RV, Repka, MA
Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently...
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From powder to tablets: Investigation of residence time distributions in a continuous manufacturing process train as basis for continuous process verification
Contributor(s):: Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus
The essence of Continuous Manufacturing (CM) resides in the fact that continuous process units are directly connected to each other forming a continuous process train. The thorough understanding of material flow in this train based on suitable sensors, including on-line process analytical...
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Granulation development in batch-to-batch and continuous processes from a quality by design perspective
Contributor(s):: Ko, Seung Jin, Lee, Ju-Hyun, Kang, Chin-Yang, Park, Jun-Bom
The process of quality by design (QbD) is of great importance in drug development. This review describes the design of experiments (DoE) method, which is an important component of QbD. DoE is predominantly divided into a screening phase and an optimization phase. The screening phase uses...
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Flexibility in Drug Product Development: A Perspective
Contributor(s):: Kapoor, Yash, Ferguson, Heidi, Skomski, Daniel, Daublain, Pierre, Troup, Gregory, Dalton, Chad, Ramasamy, Manoharan, Templeton, Allen
The process of bringing a drug to market involves innumerable decisions to refine a concept into a final product. The final product goes through extensive research and development to meet the target product profile and to obtain a product that is manufacturable at scale. Historically, this...
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Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals
Contributor(s):: Kern, Simon, Wander, Lukas, Meyer, Klas, Guhl, Svetlana, Gottu Mukkula, Anwesh, Holtkamp, Manuel, Salge, Malte, Fleischer, Christoph, Weber, Nils, King, Rudibert, Engell, Sebastian, Paul, Andrea, Pereira Remelhe, Manuel, Maiwald, Michael
Modular plants using intensified continuous processes represent an appealing concept for the production of pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes; besides, it enables plug-and-produce / reconfiguration for fast product...
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Feasibility of Using Light-Induced Fluorescence Spectroscopy for Low-Dose Formulations Monitoring and Control
Contributor(s):: Igne, Benoît, Baldasano, Caitlin, Airiau, Christian
Purpose: Light-induced fluorescence was evaluated as a process analytical tool in the development of quantitative models for themonitoring of a low-dose formulation manufacturing process. Method: The system, equipped with a probe, was positioned in a tablet press feed-frame to monitor the active...
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Feed frame: The last processing step before the tablet compaction in pharmaceutical manufacturing
Contributor(s):: Sierra-Vega, Nobel, Romañach, Rodolfo J., Méndez, Rafael
The feed frame is a force-feeding device used in the die filling process. The die filling process is crucial within pharmaceutical manufacturing to guarantee the critical quality attributes of the tablets. In recent years, interest in this unit has increased because it can affect the properties...
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Fit-for-Purpose Miniature NIR Spectroscopy for Solid Dosage Continuous Manufacturing
Contributor(s):: Karry, Krizia, Singh, Ravendra, Muzzio, Fernando
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Experimental determination of residence time distribution in continuous dry granulation
Contributor(s):: Mangal, Haress, Kleinebudde, Peter
With increasing importance of continuous manufacturing, the interest in integrating dry granulation into a continuous manufacturing line is growing. Residence time distribution measurements are of importance as they provide information about duration of materials within the process. These data...
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End-to-End Continuous Manufacturing of Pharmaceuticals: Integrated Synthesis, Purification, and Final Dosage Formation
Contributor(s):: Mascia, Salvatore, Heider, Patrick L., Zhang, Haitao, Lakerveld, Richard, Benyahia, Brahim, Barton, Paul I., Braatz, Richard D., Cooney, Charles L., Evans, James M. B., Jamison, Timothy F., Jensen, Klavs F., Myerson, Allan S., Trout, Bernhardt L.
A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug...
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Ensuring tablet quality via model-based control of a continuous direct compaction process
Contributor(s):: Kirchengast, M, Celikovic, SRehrl, J, Sacher, S, Kruisz, J, Khinast, J, Horn, M
Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders,...
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Estimation of Mass-Based Composition in Powder Mixtures Using Extended Iterative Optimization Technology (EIOT)
Contributor(s):: Shi, Zhenqi, Hermiller, James, García Muñoz, Salvador
The Extended Iterative Optimization Technology (EIOT) method is proposed as an extension to Muteki’s [I&ECR 2013;52 (35):12258–12268] Iterative Optimization Technology to address deviations from Beer–Lambert’s law in powders. The new method estimates the apparent spectrum for the pure species,...
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Evaluation of an in-line NIR spectroscopic method for the determination of the residence time in a tablet press
Contributor(s):: De Leersnyder, Fien, Vanhoorne, Valérie, Kumar, Ashish, Vervaet, Chris, De Beer, Thomas
In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on...
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Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process
Contributor(s):: Vargas, Jenny, Roman-Ospino, Andres, Sanchez, Eric, Romañach, Rodolfo
Purpos: A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis....
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Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC)
Contributor(s):: Pawar, Pallavi, Wang, Yifan, Keyvan, Golshid, Callegari, Gerardo, Cuitino, Alberto, Muzzio, Fernando
A method for predicting dissolution profiles of directly compressed tablets for a fixed sustained release formulation manufactured in a continuous direct compaction (CDC) system is presented. The methodology enables real-time release testing (RTRt). Tablets were made at a target drug...
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End-to-end continuous manufacturing of conventional compressed tablets: From flow synthesis to tableting through integrated crystallization and filtration
Contributor(s):: Domokos, A, Nagy, BGyurkes, M, Farkas, A, Tacsi, K, Pataki, H, Liu, YC, Balogh, A, Firth, P, Szilagyi, B, Marosi, G, Nagy, ZK
An end-to-end continuous pharmaceutical manufacturing process was developed for the production of conventional direct compressed tablets on a proof-of-concept level for the first time. The output reaction mixture of the flow synthesis of acetylsalicylic acid was crystallized continuously in a...
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Early detection of capping risk in pharmaceutical compacts
Contributor(s):: Xu, Xiaochi, Vallabh, Chaitanya Krishna Prasad, Hoag, Stephen W., Dave, Vivek S., Cetinkaya, Cetin
Capping is a common mechanical defect in tablet manufacturing, exhibited during or after the compression process. Predicting tablet capping in terms of process variables (e.g. compaction pressure and speed) and formulation properties is essential in pharmaceutical industry. In current work, a...
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Effective Development of PAT Capability in Pharmaceutical Manufacturing
Contributor(s):: Hammond, Steve
Over the last ten years, the path to effective development of PAT has evolved, driven by the advent of continuous manufacturing. The development and deployment of PAT used for pharmaceutical manufacturing has arrived at a point where application development has been miniaturized and streamlined....
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Development of near infrared spectroscopic calibration models for in-line determination of low drug concentration, bulk density, and relative specific void volume within a feed frame
Contributor(s):: Ortega-Zuñiga, Carlos, Pinzón-De la Rosa, Carlos, Román-Ospino, Andrés D., Serrano-Vargas, Alberto, Romañach, Rodolfo J., Mendez, Rafael
This study describes the development of a near infrared (NIR) calibration model for real time determination of drug concentration, powder density, and porosity or relative specific void volume (RSVV) of 3.00%w/w acetaminophen blends within a feed frame. The NIR calibration model was developed...
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Development of Near Infrared Spectroscopy-based Process Monitoring Methodology for Pharmaceutical Continuous Manufacturing Using an Offline Calibration Approach
Contributor(s):: Hetrick, Evan, Barnes, Lukas E, Garrett, Aaron W, Rupard, Robert G, Kramer, Timothy T, Cooper, Tony M, Myers, David P, Shi, Zhenqi, Castle, Bryan C
A near-infrared (NIR) calibration was developed using an efficient offline approach to enable a quantitative partial least-squares (PLS) chemometric model to measure and monitor the concentration of active pharmaceutical ingredients (API) in powder blends in the feed frame (FF) of a tablet press....