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  1. CONTROL OF THE CONTINUOUS VIBRATION FLUIDIZED-BED DRYING BY MEASUREMENT OF THE RELATIVE GRANULATION HUMIDITY

    09 Jun 2023 | 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...

  2. Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors

    09 Jun 2023 | 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...

  3. Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant

    09 Jul 2024 | Peer-reviewed journal | Contributor(s): Johannes Khinast, Martin Horn, Jakob Rehrl, Selma Celikovic, Johannes Poms

    ConsiGmaTM-25 is a continuous production plant integrating a twin-screw granulation, fluid bed drying, granule conditioning, and a tableting unit. The particle size distribution (PSD), active pharmaceutical ingredient (API) content, and liquid content of wet granules after twin-screw...

  4. Control strategy and methods for continuous direct compression processes

    09 Jun 2023 | Peer-reviewed journal | 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...

  5. Control strategy definition for a drug product continuous wet granulation process: Industrial case study

    09 Jun 2023 | Peer-reviewed journal | 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...

  6. Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bloomquist, CJ, Mecham, MBParadzinsky, MD, Janusziewicz, R, Warner, SB, Luft, JC, Mecham, SJ, Wang, AZ, DeSimone, JM

    Mass customization along with the ability to generate designs using medical imaging data makes 3D printing an attractive method for the fabrication of patient-tailored drug and medical devices. Herein we describe the application of Continuous Liquid Interface Production (CLIP) as a method to...

  7. Converting a batch based high -shear granulation process to a continuous dry granulation process; a demonstration with ketoprofen tablets

    09 Jun 2023 | Peer-reviewed journal | 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...

  8. Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Badruddoza, AM, Godfrin, PDMyerson, AS, Trout, BL, Doyle, PS

    Although roughly 40% of pharmaceuticals being developed are poorly water soluble, this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. In this work, a novel bottom-up approach is developed for producing and formulating...

  9. Coupling hot melt extrusion and fused deposition modeling: Critical properties for successful performance

    09 Jun 2023 | Peer-reviewed journal | 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...

  10. Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing

    13 Aug 2024 | Peer-reviewed journal | Contributor(s): Sara Fathollahi, Pauline H. M. Janssen, Bastiaan H. J. Dickhoff, Henderik W. Frijlink

    The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of...

  11. Cross-Pharma Collaboration for the Development of a Simulation Tool for the Model-Based Digital Design of Pharmaceutical Crystallization Processes (CrySiV)

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Szilagyi, Botond, Wu, Wei Lee Eren, Ayse Mackey, Jaron, Kshirsagar, Shivani, Szilagyi, Emoke, Ostergaard, Iben, Qu, Haiyan, Sinha, Kushal, Mlinar, Laurie, Pohlman, Daniel, Chen, Jie, Nere, Nandkishor, Boukerche, Moussa, Korde, Akshay, Ellis, Ryan, Lovette, Michael, Black, Simon, Jawor-Baczynska, Anna, Li, Huayu, Yang, Bing Shiou, Irdam, Erwin, Patience, Daniel, McKeown, Rahn, Ketchum, Megan, Green, Daniel A., Reddy, Venkata Ramana, Polster, Christopher, Burcham, Christopher, Jarmer, Daniel, Merritt, Jeremy Miles, Cote, Aaron, Sirota, Eric, Codan, Lorenzo, Schoell, Jochen, Liu, Yiqing Claire, Girard, Kevin P., Kulkarni, Samir A., Yang, Yihui, Quon, Justin L., Nagy, Zoltan K.

    Precompetitive collaborations on new enabling technologies for Research Article and development are becoming popular among pharmaceutical companies. The Enabling Technologies Consortium (ETC), a precompetitive collaboration of leading innovative pharmaceutical companies, identifies and executes...

  12. Crystal and Particle Engineering Strategies for Improving Powder Compression and Flow Properties to Enable Continuous Tablet Manufacturing by Direct Compression

    09 Jun 2023 | Peer-reviewed journal | 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...

  13. Crystal Population Balance Formulation and Solution Methods: A Review

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Omar, Hecham M., Rohani, Sohrab

    Crystallization is an important part of many chemical industries. Efforts are being invested to improve the performance of the crystallization process by designing novel crystallizers. An important aspect in the development of new crystallizers is the ability to describe the behavior of such...

  14. Crystal shape and size control using a plug flow crystallization configuration

    09 Jun 2023 | Peer-reviewed journal | 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....

  15. Crystal Size Control in a Continuous Tubular Crystallizer

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Besenhard, Maximilian O., Neugebauer, Peter Ho, Cheng-Da, Khinast, Johannes G.

    This paper describes a simple model-free (i.e., empirical) control strategy for crystal size tuning in a continuously operated tubular crystallizer. The crystallizer is designed for a seeded cooling crystallization process and acetylsalicylic acid crystallization from an ethanol solution was used...

  16. Crystallisation and physicochemical property characterisation of conformationally-locked co-crystals of fenamic acid derivatives

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Wittering, KE, Agnew, LRKlapwijk, AR, Robertson, K, Cousen, AJP, Cruickshank, DL, Wilson, CC

    Polymorphism in drug compounds can cause significant problems for industrial-scale production and so a method for restricting the conformational freedom of the target compound whilst retaining desired chemical properties is highly beneficial to the pharmaceutical industry. Co-crystallisation is...

  17. Crystallization of Cyclosporine in a Multistage Continuous MSMPR Crystallizer

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Alvarez, Alejandro J., Singh, Aniruddh, Myerson, Allan S.

    Crystallization processes can be batch or continuous. Potential advantages such as operating at steady state, small equipment size (relative to batch), and ability to recycle are encouraging the pharmaceutical industry to investigate continuous processes. In this work, a continuous cooling...

  18. Cyber-physical-based PAT (CPbPAT) framework for Pharma 4.0

    09 Jun 2023 | Peer-reviewed journal | 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,...

  19. Data reconciliation in the Quality-by-Design (QbD) implementation of pharmaceutical continuous tablet manufacturing

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Su, Qinglin, Bommireddy, Yasasvi, Shah Yash, Ganesh, Sudarshan, Moreno, Mariana, Liu, Jianfeng, Gonzalez, Marcial, Yazdanpanah, Nima, O'Connor, Thomas, Reklaitis, Gintaras V., Nagy, Zoltan K

    Data provided by in situ sensors is always affected by some level of impreciseness as well as uncertainty in the measurements due to process operation disturbance or material property variance. In-process data precision and reliability should be considered when implementing active product quality...

  20. Deep learning for continuous manufacturing of pharmaceutical solid dosage form

    09 Jun 2023 | Peer-reviewed journal | 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:...

  21. Deep UV Raman and fluorescence spectroscopy for real-time in situ process monitoring

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Hug, WF, Nguyen, QReid, M, Sijapati, K, Reid, RD

    Raman spectroscopy has become an increasingly common analytical method for real-time, on-line, in-line, and off-line in situ monitoring of product quality in a variety of pharmaceutical, chemical, and biological manufacturing environments, including wastewater quality [1]. The major shortcomings...

  22. Delta-mannitol to enable continuous twin-screw granulation of a highly dosed, poorly compactable formulation

    23 Jul 2024 | Peer-reviewed journal | Contributor(s): Vanhoorne, V., Almey, R., De Beer, T., Vervaet, C.

    In current study, it was investigated if the moisture-mediated polymorphic transition from δ- to β-mannitol during twin screw granulation (TSG) also took place in high drug loaded formulations and if the specific granule morphology associated with the polymorphic transition could enable tableting...

  23. Demonstrating scalability between two blender types using DEM

    12 Nov 2024 | Peer-reviewed journal | Contributor(s): Peter Boehling, Johan Remmelgas, Mohammadsadegh Salehi, Johannes Poms, Rúben Martins Fraga, Manel Bautista, Johannes G. Khinast, Emmanuela Gavi, Michela Beretta

    Powder blending is a critical step in pharmaceutical manufacturing that can impact product quality such as tablet tensile strength. This study utilized the Discrete Element Method (DEM) to investigate blending in a 5-liter mini-batch and a 2-liter Turbula blender. DEM parameters were calibrated...

  24. Design and Commercialization of an End-to-End Continuous Pharmaceutical Production Process: A Pilot Plant Case Study

    09 Jun 2023 | Peer-reviewed journal | Contributor(s): Testa, Christopher J., Hu, Chuntian, Shvedova, Khrystyna, Wu, Wei, Sayin, Ridade, Casati, Federica, Halkude, Bhakti S., Hermant, Paul, Shen, Dongying Erin, Ramnath, Anjana, Su, Qinglin, Born, Stephen C., Takizawa, Bayan, Chattopadhyay, Saptarshi, O'Connor, Thomas F., Yang, Xiaochuan, Ramanujam, Sukumar, Mascia, Salvatore

    The pharmaceutical industry faces multiple challenges (e.g., inefficient manufacturing techniques, quality control issues, and supply chain vulnerabilities) because of its current batch-wise approach to manufacturing. Recent regulatory support for continuous manufacturing and advances in...

  25. Design and Evaluation of Topical Diclofenac Sodium Gel Using Hot Melt Extrusion Technology as a Continuous Manufacturing Process with Kolliphor® P407

    23 Jul 2024 | Peer-reviewed journal | Contributor(s): Pawar, Jaywant, Narkhede, Rajkiran, Amin, Purnima, Tawde, Vaishali

    The aim of the present context was to develop and evaluate a Kolliphor® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as...