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Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 2. Validation of calibration workflow
Peer-reviewed journal | 30 Oct 2024 | Contributor(s):: Peter Toson, Marko Matić, Theresa Hörmann-Kincses, Michela Beretta, Jakob Rehrl, Johannes Poms, Peter Boehling, Thomas O’Connor, Abdollah Koolivand, Geng Tian, Scott M. Krull, Johannes G. Khinast, Johan Remmelgas, Dalibor Jajcevic
This paper is the second in a series of two that describes the application of discrete element method (DEM) and reduced order modeling to predict the effect of disturbances in the concentration of drug substance at the inlet of a continuous powder mixer on the concentration of the drug...
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Population balance model enabled digital design and uncertainty analysis framework for continuous crystallization of pharmaceuticals using an automated platform with full recycle and minimal material use
Peer-reviewed journal | 05 Sep 2024 | Contributor(s):: Wei-Lee Wu, Zoltan K. Nagy, Yash Barhate, Hemalatha Kilari
A systematic digital design framework for the development of a digital twin of a continuous crystallization process was presented using the model compound, diphenhydramine hydrochloride (DPH). The key features of the framework include operating space investigations, kinetic parameter estimation...
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Development and Application of Control Concepts for Twin-Screw Wet Granulation in the ConsiGmaTM-25: Part 2 Granule Size
Peer-reviewed journal | 04 Jun 2024 | Contributor(s):: Selma Celikovic, Johannes Poms, Johannes Khinast, Martin Horn, Jakob Rehrl
Traditional operation modes, such as running the production processes at constant process settings or within a narrow design space, do not fully exploit the advantages of continuous pharmaceutical manufacturing. Integrating Quality by Control (QbC) algorithms as a standard component of...
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RTD-based material tracking in a fully-continuous dry granulation tableting line
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Martinetz, M. C., Karttunen, A-P, Sacher, S., Wahl, P., Ketolainen, J., Khinast, J. G., Korhonen, O
Continuous manufacturing (CM) offers quality and cost-effectiveness benefits over currently dominating batch processing. One challenge that needs to be addressed when implementing CM is traceability of materials through the process, which is needed for the batch/lot definition and control...
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Process Model for Enhancing Yield in Sterile Drug Product Manufacturing
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Yabuta, K, Hirao, M, Sugiyama, H
We present a process model for enhancing the yield in the manufacturing of sterile drug products, such as injectables, eye drops, or intravenous bags. The process typically consists of compounding, filtration, filling, and visual inspection and involves raw materials of active pharmaceutical...
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Predicting Pharmaceutical Particle Size Distributions Using Kernel Mean Embedding
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Van Hauwermeiren, Daan, Stock, Michiel, De Beer, Thomas, Nopens, Ingmar
In the pharmaceutical industry, the transition to continuous manufacturing of solid dosage forms is adopted by more and more companies. For these continuous processes, high-quality process models are needed. In pharmaceutical wet granulation, a unit operation in the ConsiGmaTM-25 continuous...
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Population Balance Modeling to Predict Particle Size Distribution upon Scale-Up of a Combined Antisolvent and Cooling Crystallization of an Active Pharmaceutical Ingredient
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Rosenbaum, Tamar, Tan, Li Dummeldinger, Michael Mitchell, Niall, Engstrom, Joshua
Herein, a population balance model (PBM) for a combined cooling and antisolvent crystallization process for an active pharmaceutical ingredient (API) has been developed and utilized to predict the product particle size distribution (PSD) for two sets of four ∼35 kg scale plant batches, with...
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Parametric Study of Residence Time Distributions and Granulation Kinetics as a Basis for Process Modeling of Twin-Screw Wet Granulation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Plath, Timo, Korte, Carolin, Sivanesapillai, Rakulan, Weinhart, Thomas
Twin-screw wet granulation is a crucial unit operation in shifting from pharmaceutical batch to continuous processes, but granulation kinetics as well as residence times are yet poorly understood. Experimental findings are highly dependent on screw configuration as well as formulation, and thus...
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Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Rehrl, J, Kirchengast, MCelikovic, S, Sacher, S, Kruisz, J, Khinast, J, Horn, M
Purpose The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletization process. The new concept should improve the particle size distribution of the pellets produced. Methods Production of pellets containing an active pharmaceutical...
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Crystal shape and size control using a plug flow crystallization configuration
Peer-reviewed journal | 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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Comprehensive modelling of pharmaceutical solvation energy in different solvents
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Panwar, A, Shirazian, SSingh, M, Walker, GM
Crystallization is an important processing step in production of active pharmaceutical ingredients (API). This process is used to recover/separate the synthesized APIs for further processing to final solid dosage oral formulations. Control and understanding of crystallization are of great...
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A Virtual Plant for Integrated Continuous Manufacturing of a Carfilzomib Drug Substance Intermediate, Part 1: CDI-Promoted Amide Bond Formation
Peer-reviewed journal | 09 Jun 2023 | Contributor(s):: Içten, Elçin, Maloney, Andrew J., Beaver, Matthew G., Shen, Dongying E., Zhu, Xiaoxiang, Graham, Lauren R., Robinson, Jo A., Huggins, Seth, Allian, Ayman, Hart, Roger, Walker,Shawn D., Rolandi, Pablo, Braatz, Richard D.
This article details process characterization efforts and the development of corresponding process models to inform a process control strategy to produce a carfilzomib drug substance intermediate, morpholine amide 3. Model calibration for relevant unit operations and development of a dynamic...