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Technoeconomic Optimization of Continuous Crystallization for Three Active Pharmaceutical Ingredients: Cyclosporine, Paracetamol, and Aliskiren
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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Process modelling, design and technoeconomic evaluation for continuous paracetamol crystallisation
Contributor(s):: Jolliffe, HG, Gerogiorgis, DI
Continuous Pharmaceutical Manufacturing (CPM) has a strong potential to catalyse pharmaceutical innovation. This paper analyses Continuous Oscillatory Baffled Crystalliser (COBC) optimal design and performance for paracetamol crystallisation, via systematic modelling and nonlinear optimization...
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Nucleation kinetics of paracetamolethanol solutions from induction time experiments using Lasentec FBRM®
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
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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Multiobjective optimization of an unseeded batch cooling crystallizer for shape and size manipulation
Contributor(s):: Acevedo, David, Tandy, Yanssen, Nagy, Zoltan K.
The optimization of unseeded batch cooling crystallization systems is studied in a multiobjective framework. The length mean size and target aspect ratio (AR) of final crystals were considered as objectives, which give rise to a set of optimal solutions known as Pareto-optimal solutions. Two...
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Manipulation of ionic liquid anion-solute-antisolvent interactions for the purification of acetaminophen
Contributor(s):: Weber, CC, Kunov-Kruse, AJRogers, RD, Myerson, AS
Hydrogen bond donating cosolvents have been shown to significantly reduce the solubility of acetaminophen (AAP) in ionic liquids containing the acetate anion. Reduced solubility arises from competition for solvation by the acetate anion and can be used for the design of advanced separation...
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Mathematical Modeling, Design, and Optimization of a Multisegment Multiaddition Plug-Flow Crystallizer for Antisolvent Crystallizations
Contributor(s):: Su, Qinglin, Benyahia, Brahim Nagy, Zoltan K., Rielly, Chris D.
In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations....
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Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets
Contributor(s):: Taipale-Kovalainen, Krista, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Korhonen, Ossi
The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental...
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Determination of the kinetic parameters for the crystallization of paracetamol from water using metastable zone width experiments
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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Control of process operations and monitoring of product qualities through generic model-based in batch cooling crystallization
Contributor(s):: Samad, Noor Asma Fazli Abdul, Singh, Ravendra Sin, Gürkan Gernaey, Krist V, Gani, Rafiqul
A generic model-based framework has been developed for crystallization processes, with applications aiming at the control of process operations and the monitoring of product quality. This generic model-based framework allows the systematic development of a wide range of crystallization models for...
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Continuous manufacturing of delta mannitol by cospray drying with PVP
Contributor(s):: Vanhoorne, V., Van Bockstal, P-J., Van Snick, B., Peeters, E., Monteyne, T., Gomes, P., De Beer, T., Remon, J. P., Vervaet, C.
Mannitol is a frequently used diluent in the production of tablets due to its non-hygroscopic character and low drug interaction potential. Although the delta-polymorph of mannitol has superior tabletability in comparison to alpha- and beta-mannitol, the latter are most commonly used because...
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Compaction properties of melt coated coarse drug particles
Contributor(s):: Gren, T, Nystrom, C
Xylitol and stearic acid were applied onto the surfaces of coarse particles of paracetamol and acetylsalicylic acid by continuous multipurpose melt technology. The effect of melt coating on radial and axial tensile strength was studied and compared to that of dry mixing of paracetamol and...