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Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices
09 Jun 2023 | Contributor(s):: Dwyer, L, Kulkarni, SRuelas, L, Myerson, A
While porous silica supports have been previously studied as carriers for nanocrystalline forms of poorly water-soluble active pharmaceutical ingredients (APIs), increasing the loading of API in these matrices is of great importance if these carriers are to be used in drug formulations. A...
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Toward Continuous Crystallization of Urea-Barbituric Acid: A Polymorphic Co-Crystal System
09 Jun 2023 | Contributor(s):: Powell, KA, Bartolini, GWittering, KE, Saleemi, AN, Wilson, CC, Rielly, CD, Nagy, ZK
Pharmaceutical co-crystals are multicomponent molecular systems typically formed through hydrogen bonding of a co-former molecule with the active pharmaceutical ingredient (API). Just as many single component molecular structures can exhibit polymorphism due to the geometry of hydrogen bond...
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Technoeconomic Optimization of Continuous Crystallization for Three Active Pharmaceutical Ingredients: Cyclosporine, Paracetamol, and Aliskiren
09 Jun 2023 | Contributor(s):: Diab, S, Gerogiorgis, DI
Mixed suspension, mixed product removal (MSMPR) crystallizers are widely implemented for the continuous crystallization of active pharmaceutical ingredients (APIs), allowing enhanced efficiency, flexibility, and product quality compared to currently dominant batch crystallizer designs....
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Recent Progress in Continuous Crystallization of Pharmaceutical Products: Precise Preparation and Control
09 Jun 2023 | Contributor(s):: Ma, Yiming, Joao Macaringue, Estevao, Zhang, Teng, Gong, Junbo, Wu, Songgu, Wang, Jingkang
Crystallization, as a solid−liquid separation process, is employed to purify and isolate a great diversity of crystalline pharmaceutical products. In recent years, continuous crystallization has attracted increasing attention because of the product and process robustness as well as higher...
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Progress of Pharmaceutical Continuous Crystallization
09 Jun 2023 | Contributor(s):: Zhang, DJ, Xu, SJDu, SC, Wang, JK, Gong, JB
Crystallization is an important unit operation in the pharmaceutical industry. At present, most pharmaceutical crystallization processes are performed in batches. However, due to product variability from batch to batch and to the low productivity of batch crystallization, continuous...
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Process intensification through continuous spherical crystallization using a two-stage mixed suspension mixed product removal (MSMPR) system
09 Jun 2023 | Contributor(s):: Peña, Ramon, Nagy, Zsombor K.
Of utmost importance in the crystallization of active pharmaceutical ingredients (APIs) in the pharmaceutical industry is to produce crystals of good physical, processing, and biopharmaceutical properties. The definition of good physical properties depends on what the end goal and the drug...
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Pharmaceutical crystallisation processes from batch to continuous operation using MSMPR stages: Modelling, design, and control
09 Jun 2023 | Contributor(s):: Su, Qinglin, Nagy, Zoltan K., Rielly, Chris D.
In pharmaceuticals manufacturing, the conversion of conventional batch crystallisations to continuous mode has the potential for intensified, compact operation and more consistent production via quality-by-design. A pragmatic conversion approach is to utilise existing stirred tank batch...
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Nucleation and Growth Kinetics for Combined Cooling and Antisolvent Crystallization in a Mixed-Suspension, Mixed-Product Removal System: Estimating Solvent Dependency
09 Jun 2023 | Contributor(s):: Schall, JM, Mandur, JSBraatz, RD, Myerson, AS
Combined cooling and antisolvent crystallization is a critical unit operation in pharmaceutical manufacturing, especially for heat-sensitive or poorly soluble active pharmaceutical ingredients. The model-based design of these systems relies on the accuracy of the underlying growth and nucleation...
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No More Than Three: Technoeconomic Mixed Integer Nonlinear Programming Optimization of Mixed Suspension, Mixed Product Removal Crystallizer Cascades for Melitracen, an Antidepressant API
09 Jun 2023 | Contributor(s):: Diab, S, Gerogiorgis, DI
Mixed Suspension, Mixed Product Removal (MSMPR) crystallizers have been considered in numerous cases as a continuous mode of operation in the production of Active Pharmaceutical Ingredients (APIs). The steady-state continuous MSMPR crystallization of melitracen via cooling has been recently...
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Model-based evaluation of direct nucleation control approaches for the continuous cooling crystallization of paracetamol in a mixed suspension mixed product removal system
09 Jun 2023 | Contributor(s):: Acevedo, David, Yang, Yang Warnke, Daniel J., Nagy, Zoltan K. ;
Direct nucleation control (DNC) is a model-free feedback control approach based on the measurement of particle number in the crystallization process. The experimental implementation has demonstrated that this approach is efficient to produce large and uniform crystals in batch crystallization, or...
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Incorporating Solvent-Dependent Kinetics To Design a Multistage, Continuous, Combined Cooling/Antisolvent Crystallization Process
09 Jun 2023 | Contributor(s):: Schall, JM, Capellades, GMandur, JS, Braatz, RD, Myerson, AS
Combined cooling and antisolvent crystallization enables crystallization of many pharmaceutical products, but its process design typically neglects solvent composition influences on crystallization kinetics. This paper evaluates the influence of solvent-dependent nucleation and growth kinetics on...
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Development of continuous crystallization processes using a single-stage mixed-suspension, mixed-product removal crystallizer with recycle
09 Jun 2023 | Contributor(s):: Wong, Shin Yee, Tatusko, Adam P. Trout, Bernhardt L., Myerson, Allan S. ;
An ideal pharmaceutical crystallization process produces a pure product at a high yield while minimizing energy input, the process equipment footprint, and its complexity. A good candidate for such a process is a single-stage mixed-suspension, mixed-product removal (MSMPR) crystallizer with...
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Designs of continuous-flow pharmaceutical crystallizers: developments and practice
09 Jun 2023 | Contributor(s):: Jiang, Mo, Braatz, Richard D.
Crystallization is an effective, low-cost purification & formulation process widely applied to pharmaceuticals and fine chemicals. This review describes recent advances in Research Article on lab-scale solution-based continuous crystallization, including (1) a 5-step general design procedure; (2)...
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Development and Characterization of a Single Stage Mixed-Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit
09 Jun 2023 | Contributor(s):: Hou, GY, Power, GBarrett, M, Glennon, B, Morris, G, Zhao, Y
A continuously operated single stage mixed-suspension, mixed-product-removal (MSMPR) crystallizer using intermittent withdrawal via a dip pipe with combined pressure/vacuum was successfully developed for the manufacture of active pharmaceutical ingredients. Approximately 5.8% of the total...
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Crystallization of Cyclosporine in a Multistage Continuous MSMPR Crystallizer
09 Jun 2023 | 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...
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API Continuous Cooling and Antisolvent Crystallization for Kinetic Impurity Rejection in cGMP Manufacturing
09 Jun 2023 | Contributor(s):: Johnson, MD, Burcham, CLMay, SA, Calvin, JR, Groh, JM, Myers, SS, Webster, LP, Roberts, JC, Reddy, VR, Luciani, CV, Corrigan, AP, Spencer, RD, Moylan, R, Boyse, R, Murphy, JD, Stout, JR
Crystallization of 204 kg of final active pharmaceutical ingredient was accomplished continuously using a cascade of mixed suspension mixed product removal crystallizers in cGMP manufacturing. This article describes the journey taken to transform a set of technical to final batch crystallizations...