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Process dynamics and control of API manufacturing and purification processes
09 Jun 2023 | Contributor(s):: Sen, Maitraye, Singh, Ravendra, Ramachandran, Rohit
The pharmaceutical industries have started transitioning toward continuous mode of manufacturing recently. Due to many advantages of the continuous manufacturing over the traditional alternatives, the industries are putting huge effort to efficiently adapt the continuous processing mode. However,...
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Population Balance Model Development Verification and Validation of Cooling Crystallization of Carbamazepine
09 Jun 2023 | Contributor(s):: Liu, Yiqing C., Acevedo, David Yang, Xiaochuan Naimi, Sean, Wu, Wei-Lee, Pavurala, Naresh, Nagy, Zoltan K., O'Connor, Thomas F.
Using process modeling to understand process dynamics and potentially explore the design space of a crystallization process is difficult because of its complex nature with many factors at play, such as initial concentration, supersaturation, seeding strategy, and flow pattern. In this work, a...
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Population balance model-based multiobjective optimization of a multisegment multiaddition (MSMA) continuous plug-flow antisolvent crystallizer
09 Jun 2023 | Contributor(s):: Ridder, Bradley J., Majumder, Aniruddha, Nagy, Zoltan K.
Crystallization is a major separation process in the pharmaceutical industry. Most crystallizations are performed batchwise, but there is great incentive for converting them to continuous operations. This paper investigates the modeling, simulation, and optimization of a special antisolvent...
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Parametric, Optimization-Based Study on the Feasibility of a Multisegment Antisolvent Crystallizer for in Situ Fines Removal and Matching of Target Size Distribution
09 Jun 2023 | Contributor(s):: Ridder, Bradley J., Majumder, Aniruddha, Nagy, Zoltan K.
We have computationally investigated the use of the multisegment, multiaddition, plug-flow crystallizer (MSMA-PFC) for use in producing pharmaceutical crystals. A population balance framework was used to model the crystallization process. The dissolution of crystals can be modeled when solubility...
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Multi-scale flowsheet simulation of an integrated continuous purification-downstream pharmaceutical manufacturing process
09 Jun 2023 | Contributor(s):: Sen, M, Chaudhury, ASingh, R, John, J, Ramachandran, R
Properties of active pharmaceutical ingredients influence the critical quality attributes (CQAs) of final solid dosage forms (e. g. tablets). In the last decade, continuous manufacturing has been shown to be a promising alternative to batch processing in the pharmaceutical industry. Therefore, a...
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Modeling of pharmaceutical filtration and continuous integrated crystallization-filtration processes
09 Jun 2023 | Contributor(s):: Nagy, B, Szilagyi, BDomokos, A, Tacsi, K, Pataki, H, Marosi, G, Nagy, ZK
As continuous manufacturing is evolving in the pharmaceutical industry, continuous filtration has emerged as a bottleneck for connecting the crystallization of the active pharmaceutical ingredient with the formulation of the final drug product. This work aims the modeling of filtration to improve...
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Model development and prediction of particle size distribution, density and friability of a comilling operation in a continuous pharmaceutical manufacturing process
09 Jun 2023 | Contributor(s):: Metta, Nirupaplava, Verstraeten, Maxim Ghijs, Michael Kumar, Ashish Schafer, Elisabeth Singh, Ravendra De Beer, Thomas Nopens, Ingmar Cappuyns, Philippe, Van Assche, Ivo
The comilling process plays an important role in solid oral dosage manufacturing. In this process, the granulated products are comminuted to the required size distribution through collisions created from a rotating impeller. In addition to predicting particle size distribution, there is a need to...
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Kinetic identification and experimental validation of continuous plug flow crystallisation
09 Jun 2023 | Contributor(s):: Zhao, Yan, Kamaraju, Vamsi Krishna Hou, Guangyang Power, Graham, Donnellan, Philip, Glennon, Brian
This paper investigates the suitability of a number of potential crystallisation models to best describe the experimentally observed behaviour of the antisolvent crystallisation of benzoic acid from aqueous ethanol solution using water as an antisolvent, in a continuous plug flow crystalliser....
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Generic Framework for Crystallization Processes Using the Population Balance Model and Its Applicability
09 Jun 2023 | Contributor(s):: Shaikh, Latif J., Bari, Atul H. Ranade, Vivek V., Pandit, Aniruddha B.
A generic modeling framework for batch cooling crystallization processes has been developed to understand the crystallization process from operational and modeling point of view. The generic framework for crystallization process modeling incorporates the characteristic dimensions of crystals and...
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Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation
09 Jun 2023 | Contributor(s):: Sen, Maitraye, Rogers, Amanda Singh, Ravendra Chaudhury, Anwesha John, Joyce Ierapetritou, Marianthi G, Ramachandran, Rohit
In this work, a continuous API purification process has been optimized using an integrated flowsheet model. The simulation is dynamic in nature and includes an API purification step (crystallization), followed by filtration, drying and mixing of the API with an excipient. For the first time, this...
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Evaluation of crystallization kinetics of adipic acid in an oscillatory baffled crystallizer
09 Jun 2023 | Contributor(s):: Brown, C. J., Ni, X.
For solution crystallization, nucleation can be characterized by the maximum sub-cooling (or metastable limit), which is known to vary with numerous process parameters. The relationship between the metastable limit and cooling rate is of particular interest, as it can be utilized to derive...
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Digital Design of the Crystallization of an Active Pharmaceutical Ingredient Using a Population Balance Model with a Novel Size Dependent Growth Rate Expression. From Development of a Digital Twin to In Silico Optimization and Experimental Validation
09 Jun 2023 | Contributor(s):: Szilágyi, Botond, Eren, Ayşe Quon, Justin L. Papageorgiou, Charles D., Nagy, Zoltán K.
Prediction and control of the product properties in crystallization processes are practical challenges in the pharmaceutical industry. Effective crystallization process design and operation techniques are needed to meet the critical quality attributes (CQAs) and minimize batch-to-batch variation....
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Cross-Pharma Collaboration for the Development of a Simulation Tool for the Model-Based Digital Design of Pharmaceutical Crystallization Processes (CrySiV)
09 Jun 2023 | 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...
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Crystal Population Balance Formulation and Solution Methods: A Review
09 Jun 2023 | 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...
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Closed-loop feedback control of a continuous pharmaceutical tablet manufacturing process via wet granulation
09 Jun 2023 | Contributor(s):: Singh, Ravendra, Barrasso, Dana Chaudhury, Anwesha Sen, Maitraye Ierapetritou, Marianthi Ramachandran, Rohit
The wet granulation route of tablet manufacturing in a pharmaceutical manufacturing process is very common due to its numerous processing advantages such as enhanced powder flow and decreased segregation. However, this route is still operated in batch mode with little (if any) usage of an...
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A multi-scale hybrid CFD-DEM-PBM description of a fluid-bed granulation process
09 Jun 2023 | Contributor(s):: Sen, Maitraye, Barrasso, Dana Singh, Ravendra, Ramachandran, Rohit
In this study, a hybrid multi-scale model has been developed for a continuous fluid bed wet granulation process by dynamically coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and population balance model (PBM). In this process, the granules are formed by spraying...