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Template-induced nucleation for controlling crystal polymorphism: from molecular mechanisms to applications in pharmaceutical processing
09 Jun 2023 | Contributor(s):: Parambil, JV, Poornachary, SKHeng, JYY, Tan, RBH
Over the last two decades, the use of template surfaces to induce heterogeneous crystal nucleation has been explored primarily to address two different goals: first, as an alternative to the conventional seeding technique used for polymorph control and, second, as a technique to promote the...
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Solvothermal Crystallization Kinetics and Control of Crystal Size Distribution of MOF-808 in a Continuous Flow Reactor
09 Jun 2023 | Contributor(s):: Bagi, Sujay D., Myerson, Allan S. Román-Leshkov, Yuriy, Román-Leshkov, Yuriy
A fundamental understanding of the crystallization pathways for metal-organic frameworks (MOFs) allows for exploring the untapped combinatorial space of the organic and inorganic building units, creating possibilities to synthesize highly crystalline frameworks with desired physicochemical...
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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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Optimization in seeded cooling crystallization: A parameter estimation and dynamic optimization study
09 Jun 2023 | Contributor(s):: Nowee, S. Mostafa, Abbas, Ali, Romagnoli, Jose A.
In this solution crystallization study, a population balance model that predicts the crystal size distribution (CSD) is used for targeting, by optimization, the product mean size and the coefficient of variation of the final CSD. The model is robust over a wide range of conditions and predicts...
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Nucleation kinetics of paracetamolethanol solutions from induction time experiments using Lasentec FBRM®
09 Jun 2023 | Contributor(s):: Mitchell, Niall A., Ó'Ciardhá, Clifford T., Frawley, Patrick J.
A study of the nucleation kinetics for cooling crystallisation of paracetamolethanol solutions in a batch reactor is described in this paper. Induction time experiments were conducted in order to estimate the nucleation kinetics of the system. Measured induction times can be affected by numerous...
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Nucleation kinetics of paracetamolethanol solutions from metastable zone widths
09 Jun 2023 | Contributor(s):: Mitchell, Niall A., Frawley, Patrick J.
A study of the nucleation kinetics for a cooling crystallisation of paracetamolethanol solutions in a batch reactor is described in this paper. Metastable zone width (MSZW) experiments were conducted in order to estimate the nucleation kinetics of the system. Measured MSZWs can be affected by...
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Nucleation Studies of Active Pharmaceutical Ingredients in an Air-Segmented Microfluidic Drop-Based Crystallizer
09 Jun 2023 | Contributor(s):: Lu, Jennifer, Litster, James D., Nagy, Zoltan K.
In this work, an innovative experimental platform to study the nucleation behavior of an active pharmaceutical ingredient (API) using a gas-segmented flow produced by a microfluidic T-junction device with fine perfluoroalkoxy alkane (PFA) tubing is presented. In the experiments, a continuous...
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Model-Based Systematic Design and Analysis Approach for Unseeded Combined Cooling and Antisolvent Crystallization (CCAC) Systems
09 Jun 2023 | Contributor(s):: Yang, Yang, Nagy, Zoltan K.
A novel model-based systematic analysis and design approach for unseeded combined cooling and antisolvent crystallization (CCAC) processes has been proposed and evaluated for the crystallization of aspirin in ethanol–water mixture. The approach can be easily implemented in practice using...
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Determination of the kinetic parameters for the crystallization of paracetamol from water using metastable zone width experiments
09 Jun 2023 | Contributor(s):: Nagy, Zoltan K., Fujiwara, Mitsuko Woo, Xing Yi, Braatz, Richard D. ;
A new approach for the estimation of kinetic parameters of crystallization from data obtained during the determination of metastable zone width is presented. The method is based on a simplified dynamic model of the system, which combines the population balance and mass balance, as well as...
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Continuous-flow tubular crystallization in slugs spontaneously induced by hydrodynamics
09 Jun 2023 | Contributor(s):: Jiang, Mo, Zhu, Zhilong Jimenez, Ernesto Papageorgiou, Charles D., Waetzig, Josh, Hardy, Andrew, Langston, Marianne, Braatz, Richard D.
A novel continuous crystallizer design is described with the potential to provide improved control of crystal properties, improved process reproducibility, and reduced scale-up risk. Liquid and gas are introduced into one end of the tube at flow rates selected to spontaneously generate...
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Continuous Pharmaceutical Crystallization from Solution
09 Jun 2023 | Contributor(s):: Price, CJ
Brings together the essential know-how for anyone working in drug manufacturing, as well as chemical, food, and pharmaceutical scientists working on continuous processing
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Continuous Heterogeneous Crystallization on Excipient Surfaces
09 Jun 2023 | Contributor(s):: Yazdanpanah, Nimaa, Testa, Christopher J., Perala, Siva R. K., Jensen, Keith D., Braatz, Richard D., Myerson, Allan S., Trout, Bernhardt L.
A novel continuous heterogeneous crystallization process is, developed in which the active pharmaceutical ingredient (API) is crystallized directly on the surface of an excipient within the crystallizer. The produet is subsequently dried and formed into tablets without the need for complex...
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Continuous Crystallization of Aliskiren Hemifumarate
09 Jun 2023 | Contributor(s):: Quon, JL, Zhang, HAlvarez, A, Evans, J, Myerson, AS, Trout, BL
Active ingredients in most pharmaceutical products are complex organic molecules that require crystallization as a purification and isolation step that results in a pure product at a high process yield. Knowledge of the operating conditions required to obtain crystals with the desired crystal...
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Comparative investigation of supersaturation and automated direct nucleation control of crystal size distributions using ATR-UV/vis spectroscopy and FBRM
09 Jun 2023 | Contributor(s):: Saleemi, Ali N., Rielly, Chris D., Nagy, Zoltan K.
The paper presents a thorough evaluation of different control strategies used in cooling crystallization, namely, unseeded linear cooling, seeded linear cooling, supersaturation control, and automated direct nucleation control. The sensitivity and robustness of supersaturation and automated...
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Biocompatible Alginate Microgel Particles as Heteronucleants and Encapsulating Vehicles for Hydrophilic and Hydrophobic Drugs
09 Jun 2023 | Contributor(s):: Eral, HB, Lopez-Mejias, VO'Mahony, M, Trout, BL, Myerson, AS, Doyle, PS
Biocompatible materials that can control crystallization while carrying large amounts of active pharmaceutical ingredients (APIs) with diverse chemical properties are in demand in industrial practice. In this study, we investigate the utility of biocompatible alginate (ALG) hydrogels as a...
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Asymmetric distribution in twin screw granulation
09 Jun 2023 | Contributor(s):: Seem, Tim Chan, Rowson, Neil A., Gabbott, Ian, de Matas, Marcel, Reynolds, Gavin K., Ingram, Andy
Positron Emission Particle Tracking (PEPT) was successfully employed to validate measured transverse asymmetry in material distribution in the conveying zones of a Twin Screw Granulator (TSG). Flow asymmetry was established to be a property of the granulator geometry and dependent on fill level....
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Application of process analytical technology-based feedback control for the crystallization of pharmaceuticals in porous media
09 Jun 2023 | Contributor(s):: Acevedo, David A., Ling, Jing Chadwick, Keith, Nagy, Zoltak K. ;
The purpose of this work is to implement a feedback control approach during the cooling crystallization of paracetamol (PCM) in porous media to increase the amount of PCM in the alginate beads (i.e., drug loading) and minimize the heterogeneous nucleation occurring in the bulk system. Two types...
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Application of Model-Free and Model-Based Quality-by-Control (QbC) for the Efficient Design of Pharmaceutical Crystallization Processes
09 Jun 2023 | Contributor(s):: Szilagyi, Botond, Eren, Ayse Quon, Justin L. Papageorgiou, Charles D., Nagy, Zoltan K.
The design of pharmaceutical crystallization processes is a challenging engineering problem because of the specific and versatile quality requirements of the end-product, amplified by the tight regulatory standards. The current industrial standard for crystallization process design is based on...
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A Stochastic Population Balance Equation Model for Nucleation and Growth of Crystals with Multiple Polymorphs
09 Jun 2023 | Contributor(s):: Maggioni, Giovanni, Mazzotti, Marco
Understanding polymorph crystallization is important due to the different properties, such as bioavailability or crystal shape, exhibited by the different crystal forms. In this work, we present a model, based on population balance equations, describing the unseeded crystallization by cooling of...
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A novel robust digital design of a network of industrial continuous cooling crystallizers of dextrose monohydrate: From laboratory experiments to industrial application
09 Jun 2023 | Contributor(s):: Nagy, Zoltan K., Szilagyi, Botond Pal, Kanjakha, Tabar, Iman Beheshti ;
This paper presents the first-ever industrial application of the digital design of a complex, large-scale industrial continuous crystallization network. The aim of the work is to optimize a large-scale continuous crystallization network used for the purification of dextrose monohydrate, by...