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Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying
09 Jun 2023 | Contributor(s):: Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus
Continuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase...
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Pharmaceutical application of multivariate modelling techniques: a review on the manufacturing of tablets
09 Jun 2023 | Contributor(s):: Shi, Guolin, Lin, Longfei, Liu, Yuling, Chen, Gongsen, Luo, Yuting, Wu, Yanqiu, Li, Hui
The tablet manufacturing process is a complex system, especially in continuous manufacturing (CM). It includes multiple unit operations, such as mixing, granulation, and tableting. In tablet manufacturing, critical quality attributes are influenced by multiple factorial relationships between...
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Pharmaceutical crystallisation processes from batch to continuous operation using MSMPR stages: Modelling, design, and control
09 Jun 2023 | Contributor(s):: Su, Qinglin, Nagy, Zoltan K., Rielly, Chris D.
In pharmaceuticals manufacturing, the conversion of conventional batch crystallisations to continuous mode has the potential for intensified, compact operation and more consistent production via quality-by-design. A pragmatic conversion approach is to utilise existing stirred tank batch...
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Orthogonal Redundant Monitoring of a New Continuous Fluid-Bed Dryer for Pharmaceutical Processing by Means of Mass and Energy Balance Calculations and Spectroscopic Techniques
09 Jun 2023 | Contributor(s):: Pauli, Victoria, Elbaz, Frantz, Kleinebudde, Peter, Krumme, Markus
In line with the ongoing shift from batch to continuous pharmaceutical production of solid oral dosage forms, a novel continuous fluid-bed dryer was developed. The forced feed nature of the Glatt GPCG2 CM fluid-bed dryer allows continuous, first-in-first-out drying of wet granulate materials...
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On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Implementation and in Situ Control of Downstream Production
09 Jun 2023 | Contributor(s):: Capellades, Gerard, Neurohr, Clemence Briggs, Naomi Rapp, Kersten, Hammersmith, Gregory, Brancazio, David, Derksen, Bridget, Myerson, Allan S.
Traditional pharmaceutical manufacturing operates around a supply chain that is subject to complex logistics and is vulnerable to spikes in demand and interruptions. In this context, continuous pharmaceutical manufacturing in portable, refrigerator-sized factories is a promising solution with...
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New approach to optimizing risk management of the sticking problem using scale-independent critical material attributes and the quantitative process parameter
09 Jun 2023 | Contributor(s):: Ando, Hirotaka, Hara, Yuko, Sato, Kazunari, Dohi, Masafumi, Hakomori, Tadashi, Yonemochi, Etsuo
In pharmaceutical manufacturing of solid formulations, blending with a lubricant is a key process in preventing sticking during compression. Sticking not only results in tablets with a disfigured appearance but also brings about the interruption of continuous operations. The aim of our study was...
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Monitoring the concentration of flowing pharmaceutical powders in a tableting feed frame
09 Jun 2023 | Contributor(s):: Gosselin, Ryan, Durão, Pedro, Abatzoglou, Nicolas, Guay, Jean-Maxime
The use of process analytical technology (PAT) tools is increasing steadily in the pharmaceutical industry. Such tools are now located throughout the process. When producing tablets, the tableting step itself may be the ideal moment to assess final product composition. Being the last unit...
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Model-predictive design, control and optimization of pharmaceutical process
09 Jun 2023 | Contributor(s):: Muzzio, F, Singh, R Chaudhury, A Rogers, A Ramachandran, R, Ierapetritou, M
Applying model-predictive methods and a continuous process-control framework to a continuous tablet-manufacturing process. Currently, there is a high level of interest in the pharmaceutical industry in continuous-manufacturing strategies, integrated with online-monitoring tools, that are...
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Model-Predictive Design, Control, and Optimization
09 Jun 2023 | Contributor(s):: Muzzio, Fernando, Singh, Ravendra Chaudhury, Anwesha Rogers, Amanda Ramachandran, Rohit, Ierapetritou, Marianthi
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Modeling and Control of Roller Compaction for Pharmaceutical Manufacturing. Part I: Process Dynamics and Control Framework
09 Jun 2023 | Contributor(s):: Hsu, Shuo-Huan, Venkatasubramanian, Venkat, Reklaitis, Gintaras V.
We derive a dynamic model for roller compaction process based on Johanson’s rolling theory, which is used to predict the stress and density profiles during the compaction and the material balance equation which describes the roll gap change. The proposed model considers the relationship between...
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Loss-in-Weight Feeding Trials Case Study: Pharmaceutical Formulation
09 Jun 2023 | Contributor(s):: Engisch, WE, Muzzio, FJ
This article presents a case study of a continuous feeding strategy for five pharmaceutical components (active pharmaceutical ingredient (API), Prosolv HD90, crospovidone, magnesium stearate, and colloidal silicon dioxide), for the purpose of developing a direct compression continuous...
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Integrated continuous manufacturing in pharmaceutical industry: current eolutionary steps toward revolutionary future
09 Jun 2023 | Contributor(s):: Nada A Helal, Ola Elnoweam, Heba Abdullah Eassa, Ahmed M Amer, Mohamed Ashraf Eltokhy, Mohamed A Helal, Heba A Fayyaz, Mohamed Ismail Nonou
Continuous manufacturing (CM) has the potential to provide pharmaceutical products with better quality, improved yield and with reduced cost and time. Moreover, ease of scale-up, small manufacturing footprint and on-line/in-line monitoring and control of the process are other merits for CM....
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Implementing Feedback Granule Size Control in a Continuous DryGranulation Line Using Controlled Impeller Speed of the GranulationUnit, Compaction Force and Gap Width
09 Jun 2023 | Contributor(s):: Wilms, Annika, Teske, Andreas, Meier, Robin, Wiedey, Raphael, Kleinebudde, Peter
Purpose: In continuous manufacturing of pharmaceuticals, dry granulation is of interest because of its large throughput capacity and energy efficiency. In order to manufacture solid oral dosage forms continuously, valid control strategies for critical quality attributes should be established. To...
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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
09 Jun 2023 | 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
09 Jun 2023 | 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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Exceptional Events Management Applied to Roller Compaction of Pharmaceutical Powders
09 Jun 2023 | Contributor(s):: Hamdan, Intan Munirah, Reklaitis, Gintaras V., Venkatasubramanian, Venkat
Introduction This study focuses on the development and implementation of an Exceptional Events Management (EEM) framework that detects, diagnoses, and mitigates exceptional events inherent to particulate processes that are prevalent in the pharmaceutical industry. Methods The EEM framework...
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Experimental determination of residence time distribution in continuous dry granulation
09 Jun 2023 | 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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Ensuring tablet quality via model-based control of a continuous direct compaction process
09 Jun 2023 | 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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Development of Near Infrared Spectroscopy-based Process Monitoring Methodology for Pharmaceutical Continuous Manufacturing Using an Offline Calibration Approach
09 Jun 2023 | 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....
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Direct compaction: An update of materials, trouble-shooting, and application
09 Jun 2023 | Contributor(s):: Li, Z, Zhao, LJLin, X, Shen, L, Feng, Y
Direct compaction (DC) is the preferred choice for tablet manufacturing; however, only less than 20% of active pharmaceutical ingredients could be compacted via DC as its high requirement for functional properties of materials. Materials with improper functionalities could lead to serious...
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Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame
09 Jun 2023 | Contributor(s):: Li, Yi, Anderson, Carl A, Drennen, James K, Airiau, Christian, Igne, Benoît
Process analytical technology (PAT) has shown great potential for in-line tableting process monitoring. The study focuses on the development and validation of an in-line near-infrared (NIR) spectroscopic method for the determination of content uniformity of blends in a tablet feed frame. An...
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Development of a Controlled Continuous Low-Dose Feeding Process
09 Jun 2023 | Contributor(s):: Fathollahi, Sara, Kruisz, Julia, Sacher, Stephan, Rehrl, Jakob, Escotet-Espinoza, M. Sebastian, DiNunzio, James, Glasser, Benjamin J., Khinast, Johannes G.
This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum...
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Determination of Residence Time Distribution in a Continuous Powder Mixing Process With Supervised and Unsupervised Modeling of In-line Near Infrared (NIR) Spectroscopic Data
09 Jun 2023 | Contributor(s):: Pedersen, Troels, Karttunen, Anssi-Pekka, Korhonen, Ossi, Wu, Jian Xiong, Naelapää, Kaisa, Skibsted, Erik, Rantanen, Jukka
Successful implementation of continuous manufacturing processes requires robust methods to assess and control product quality in a real-time mode. In this study, the residence time distribution of a continuous powder mixing process was investigated via pulse tracer experiments using near infrared...
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Crystal shape and size control using a plug flow crystallization configuration
09 Jun 2023 | Contributor(s):: Sang-Il Kwon, Joseph, Nayhouse, Michael Orkoulas, Gerassimos
This work focuses on modeling and control of a continuous plug flow crystallizer (PFC) used to produce tetragonal hen-egg-white (HEW) lysozyme crystals and proposes an optimization-based control scheme to produce crystals with desired size and shape distributions in the presence of disturbances....
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Control of Drug-Excipient Particle Attributes with Droplet Microfluidic-based Extractive Solidification Enables Improved Powder Rheology
09 Jun 2023 | Contributor(s):: Ng, DZL, Nelson, AZWard, G, Lai, D, Doyle, PS, Khan, SA
Purpose Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients(APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the...