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Development and Use of a Residence Time Distribution (RTD) Model Control Strategy for a Continuous Manufacturing Drug Product Pharmaceutical Process
Contributor(s):: Hurley, Samantha, Tantuccio, Anthony, Escotet-Espinoza, Manuel Sebastian, Flamm, Matthew, Metzger, Matthew
Residence-time-distribution (RTD)-based models are key to understanding the mixing dynamics of continuous manufacturing systems. Such models can allow for material traceability throughout the process and can provide the ability for removal of non-conforming material from the finished product....
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Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press
Contributor(s):: De Leersnyder, Fien, Peeters, Elisabeth, Djalabi, Hasna, Vanhoorne, Valérie, Van Snick, Bernd, Hong, Ke, Hammond, Stephen, Liu, Angela, Ziemons, Eric, Vervaet, Chris, De Beer, Thomas
A calibration model for in-line API quantification based on near infrared (NIR) spectra collection during tableting in the tablet press feed frame was developed and validated. First, the measurement set-up was optimised and the effect of filling degree of the feed frame on the NIR spectra was...
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Development of a continuous direct compression platform for low-dose drug products
Contributor(s):: Van Snick, B, Holman, J, Vanhoorne, V, Kumar, A, De Beer, T, Remon, JP, Vervaet, C
In this work a continuous direct compression process was developed for a low-dosed drug product. Each unit operation of the GEA CDC-50 system was thoroughly investigated. This paper aimed to tackle the macroscopic and microscopic blend uniformity challenges inherently associated with continuous...
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Detailed Analysis of the Online Near-Infrared Spectra of Pharmaceutical Blend in a Rotary Tablet Press Feed Frame
Contributor(s):: Šašić, Slobodan, Blackwood, Daniel, Liu, Angela, Ward, Howard W, Clarke, Hugh
The present study is an in-depth analysis of the online near-infrared (NIR) spectra acquired with a spectrometer mounted on the rotary tablet press feed frame. A 3.5% active pharmaceutical ingredient (API) formulation is analyzed. An attempt is made to determine the API univariately via the 2nd...
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Determination of a quantitative relationship between material properties, process settings and screw feeding behavior via multivariate data-analysis
Contributor(s):: Bekaert, B, Penne, L, Grymonpre, W, Van Snick, B, Dhondt, J, Boeckx, J, Vogeleer, J, De Beer, T, Vervaet, C, Vanhoorne, V
In this study, a quantitative relationship between material properties, process settings and screw feeding responses of a high-throughput feeder was established via multivariate models (PLS). Thirteen divergent powders were selected and characterized for 44 material property descriptors. During...
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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
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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Developing a framework to model the primary drying step of a continuous freeze-drying process based on infrared radiation
Contributor(s):: Van Bockstal, Pieter-Jan, Corver, Jos, Mortier, Severine Therese F. C., De Meyer, Laurens, Nopens, Ingmar, Gernaey, Krist V., De Beer, Thomas
The continuous freeze-drying concept based on spinning the vials during freezing and on non-contact energy transfer via infrared (IR) radiation during drying, improves process efficiency and product quality (uniformity) compared to conventional batch freeze-drying. Automated control of this...
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Development and Application of a Business Case Model for a Stream Sampler in the Pharmaceutical Industry
Contributor(s):: Fontalvo-Lascano, María A, Alvarado-Hernández, Bárbara B., Conde, Carlos, Sánchez, Eric J., Méndez-Piñero, Mayra I., Romañach, Rodolfo
Purpose: A template to prepare a business case for Process Analytical Technology (PAT) and Continuous Manufacturing (CM) projects is presented in this study. Business cases are necessary tools used in different organizations to present new projects for management evaluation. As new ways of...
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Cyber-physical-based PAT (CPbPAT) framework for Pharma 4.0
Contributor(s):: Barenji, Reza Vatankhah, Akdag, Yagmur, Yet, Barbaros., Oner, Levent
Industry 4.0 aims to integrate manufacturing operations into a seamless digital whole by incorporating flexibility, agility, re-configurability, and sustainability. The result of this integration is a “smart factory” that is more lean, agile, and flexible in operations. There are valid reasons,...
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Deep learning for continuous manufacturing of pharmaceutical solid dosage form
Contributor(s):: Roggo, Yves, Jelsch, Morgane, Heger, Philipp, Ensslin, Simon, Krumme, Markus
Continuous Manufacturing (CM) of pharmaceutical drug products is a new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line for production of solid dosage forms was investigated. The line was composed of the subsequent continuous unit:...
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Design of Condition-based Maintenance Framework for Process Operations Management in Pharmaceutical Continuous Manufacturing
Contributor(s):: Ganesh, Sudarshan, Su, Qinglin, Vo, Le Bao Dan, Pepka, Nolan, Rentz, Benjamin, Vann, Lucas, Yazdanpanah, Nima, O'Connor, Thomas, Nagy, Zoltan K., Reklaitis, Gintaras V.
Continuous manufacturing, an emerging technology in the pharmaceutical industry, has the potential to increase the efficiency, and agility of pharmaceutical manufacturing processes. To realize these potential benefits of continuous operations, effectively managing materials, equipment, analyzers,...
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Converting a batch based high -shear granulation process to a continuous dry granulation process; a demonstration with ketoprofen tablets
Contributor(s):: Taipale-Kovalainen, Krista, Ketolainen, Jarkko, Korhonen, Ossi, Ervasti, Tuomas
When one wishes to convert a batch based manufacturing process of an existing tablet product to a continuous process, there are several available strategies which can be adopted. Theoretically, the most straightforward way would be to proceed with the corresponding processing principles, for...
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Coupling hot melt extrusion and fused deposition modeling: Critical properties for successful performance
Contributor(s):: Bandari, Suresh, Nyavanandi, Dinesha, Dumpa, Nagireddy, Repka, Michael A.
Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused deposition modeling (FDM) 3D printing has been the most extensively investigated for patient-focused dosage. HME technology can be...
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Crystal and Particle Engineering Strategies for Improving Powder Compression and Flow Properties to Enable Continuous Tablet Manufacturing by Direct Compression
Contributor(s):: Chattoraj, Sayantan, Sun, Changquan Calvin
Continuous manufacturing of tablets has many advantages, including batch size flexibility, demand-adaptive scale up or scale down, consistent product quality, small operational foot print, and increased manufacturing efficiency. Simplicity makes direct compression the most suitable process for...
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CONTROL OF THE CONTINUOUS VIBRATION FLUIDIZED-BED DRYING BY MEASUREMENT OF THE RELATIVE GRANULATION HUMIDITY
Contributor(s):: FUCHS, G, PATT, L, HABERSTROH, A
This article describes a method to measure the relative granulation humidity in the pharmaceutical production. The method is employed as on-line process controll for monitoring the continuous fluidized-bed drying process. The dryer settings are adjusted according to the relative humidity...
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Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors
Contributor(s):: Rehrl, J, Karttunen, APNicolai, N, Hormann, T, Horn, M, Korhonen, O, Nopens, I, De, Beer, T, Khinast, JG
One major advantage of continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the...
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Control strategy and methods for continuous direct compression processes
Contributor(s):: Suzuki, Yasuhiro, Sugiyama, Hirokazu, Kano, Manabu, Shimono, Ryutaro, Shimada, Gosuke, Furukawa, Ryoichi, Mano, Eichi, Motoyama, Keiichi, Koide, Tatsuo, Matsui, Yasuhiro, Kurasaki, Kazuki, Takayama, Issei, Hikage, Shunin, Katori, Noriko, Kikuchi, Masahiko, Sakai, Hiroshi, Matsuda, Yoshihiro
We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio...
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Control strategy definition for a drug product continuous wet granulation process: Industrial case study
Contributor(s):: Chavez, Pierre-François, Stauffer, Fanny, Eeckman, Frédéric, Bostijn, Nils, Didion, David, Schaefer, Cédric, Yang, Hong, El Aalamat, Yousef, Lories, Xavier, Warman, Martin, Mathieu, Benoit, Mantanus, Jérôme
This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with...
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Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API
Contributor(s):: Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...
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Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach
Contributor(s):: Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, Leys, Jan, Klingeleers, Didier, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
Despite significant advances in the Research Article domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent...
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Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations
Contributor(s):: Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...
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Continuous twin screw granulation: Influence of process variables on granule and tablet quality
Contributor(s):: Vercruysse, J., Diaz, D. Cordoba, Peeters, E., Fonteyne, M., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Veryaet, C.
The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, alpha-lactose monohydrate...
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Continuous twin screw granulation: Robustness of lactose/MCC-based formulations
Contributor(s):: Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie
In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...
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Continuous twin screw wet granulation: The combined effect of process parameters on residence time, particle size, and granule morphology
Contributor(s):: Shirazian, Saeed, Zeglinski, Jacek, Darwish, Shaza, Kuhs, Manuel, Albadarin, Ahmad B., Croker, Denise M., Walker, Gavin M.
In this study, a set of 24 experiments was designed to understand the combined effect of different process parameters, i.e. material feed rate, liquid-to-solid (L/S) ratio, screw speed, and screw configuration on the residence time distribution, granule morphology, and particle size distribution...
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Continuous quantitative monitoring of powder mixing dynamics by near-infrared spectroscopy
Contributor(s):: Koller, DM, Posch, A, Horl, G, Voura, C, Radl, S, Urbanetz, N, Fraser, SD, Tritthart, W, Reiter, F, Schlingmann, M, Khinast, JG
FT-NIR spectroscopy with a fiber optical reflection probe was applied as a process analytical technology tool for the continuous quantitative in-line monitoring of pharmaceutical powder mixing processes in a bladed mixer. Two powders, acetyl salicylic acid as an active pharmaceutical ingredient...