Application of PAT-Based Feedback Control Approaches in Pharmaceutical Crystallization

Crystallization is one of the important unit operations for the separation and purification of solid products in the chemical, pharmaceutical, and pesticide industries, especially for realizing high-end, high-value solid products. The precise control of the solution crystallization process determines the polymorph, crystal shape, size, and size distribution of the crystal product, which is of great significance to improve product quality and production efficiency. In order to develop the crystallization process in a scientific method that is based on process parameters and data, process analysis technology (PAT) has become an important enabling platform. In this paper, we review the development of PAT in the field of crystallization in recent years. Based on the current research status of drug crystallization process control, the monitoring methods and control strategies of feedback control in the crystallization process were systematically summarized. The focus is on the application of model-free feedback control strategies based on the solution and solid information collected by various online monitoring equipment in product engineering, including improving particle size distribution, achieving polymorphic control, and improving purity. In this paper, the challenges of feedback control strategy in the crystallization process are also discussed, and the development trend of the feedback control strategy has been prospected.

[2]  Kai Sundmacher,et al.  Optimal Control of Crystal Shapes in Batch Crystallization Experiments by Growth-Dissolution Cycles , 2016 .

[3]  Zoltan K. Nagy,et al.  Process Intensification through Continuous Spherical Crystallization Using a Two-Stage Mixed Suspension Mixed Product Removal (MSMPR) System , 2015 .

[4]  Richard D. Braatz,et al.  Advanced control of crystallization processes , 2002, Annu. Rev. Control..

[5]  Ting Lu,et al.  Parameters soft-sensing based on neural network in crystallizing process of cane sugar , 2002, Proceedings of the 4th World Congress on Intelligent Control and Automation (Cat. No.02EX527).

[6]  Z. Nagy,et al.  PAT-based design of agrochemical co-crystallization processes: A case-study for the selective crystallization of 1:1 and 3:2 co-crystals of p-toluenesulfonamide/triphenylphosphine oxide , 2016 .

[7]  H. Qu,et al.  Polymorphic Control and Scale-Up Strategy for Antisolvent Crystallization Using Direct Nucleation Control , 2020 .

[8]  Thomas Scheper,et al.  In‐situ‐Mikroskopie zur Online‐Überwachung von Enzymträgern und Zweiphasenprozessen , 2011 .

[9]  L. L. Simon,et al.  Comparison of external bulk video imaging with focused beam reflectance measurement and ultra-violet visible spectroscopy for metastable zone identification in food and pharmaceutical crystallization processes , 2009 .

[10]  George Zhou,et al.  Evolution and Application of an Automated Platform for the Development of Crystallization Processes , 2013 .

[11]  R. Braatz,et al.  Direct design of pharmaceutical antisolvent crystallization through concentration control , 2006 .

[12]  J. Rawlings,et al.  Industrial crystallization process control , 2006, IEEE Control Systems.

[13]  Manfred Morari,et al.  Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. IV. Modeling and Control of Dissolution , 2019, Crystal Growth & Design.

[14]  Yang Yang,et al.  Model-Based Optimization of Cooling Crystallization of Active Pharmaceutical Ingredients Undergoing Thermal Degradation , 2019, Crystal Growth & Design.

[15]  Zoltan K. Nagy,et al.  Real-Time Image Processing Based Online Feedback Control System for Cooling Batch Crystallization , 2017 .

[16]  Z. Nagy,et al.  Investigation of the Effect of Temperature Cycling on Surface Features of Sulfathiazole Crystals during Seeded Batch Cooling Crystallization , 2010 .

[17]  Thomas Rades,et al.  An overview of recent studies on the analysis of pharmaceutical polymorphs. , 2011, Journal of pharmaceutical and biomedical analysis.

[18]  H. Kramer,et al.  Application of Seeding as a Process Actuator in a Model Predictive Control Framework for Fed‐Batch Crystallization of Ammonium Sulphate , 2007 .

[19]  H. Mangal,et al.  Experimental determination of residence time distribution in continuous dry granulation. , 2017, International journal of pharmaceutics.

[20]  Zoltan K. Nagy,et al.  Model based robust control approach for batch crystallization product design , 2009, Comput. Chem. Eng..

[21]  Zoltan K. Nagy,et al.  Tuning Crystal Morphology of Succinic Acid Using a Polymer Additive , 2016 .

[22]  George Zhou,et al.  A Novel Crystallization Methodology To Ensure Isolation of the Most Stable Crystal Form , 2009 .

[23]  H. Kramer,et al.  A Comparative Study of ATR-FTIR and FT-NIR Spectroscopy for In-Situ Concentration Monitoring during Batch Cooling Crystallization Processes , 2010 .

[25]  E. Hæggström,et al.  Closed‐Loop Control of Reactive Crystallization PART II: Polymorphism Control of L‐Glutamic Acid by Sonocrystallization and Seeding , 2010 .

[26]  Thermodynamic Polymorph Selection in Enantiotropic Systems Using Supersaturation-Controlled Batch and Semibatch Cooling Crystallization , 2019, Crystal Growth & Design.

[27]  A. Randolph,et al.  A population balance for countable entities , 1964 .

[28]  Richard D Braatz,et al.  Advances and new directions in crystallization control. , 2012, Annual review of chemical and biomolecular engineering.

[29]  Ali N. Saleemi,et al.  The impact of direct nucleation control on crystal size distribution in pharmaceutical crystallization processes , 2009 .

[30]  N. Kubota,et al.  Process Control of Seeded Batch Cooling Crystallization of the Metastable α-Form Glycine Using an In-Situ ATR-FTIR Spectrometer and an In-Situ FBRM Particle Counter , 2004 .

[31]  K. Roberts,et al.  In-Process ATR-FTIR Spectroscopy for Closed-Loop Supersaturation Control of a Batch Crystallizer Producing Monosodium Glutamate Crystals of Defined Size , 2003 .

[32]  M. Takimoto-Kamimura,et al.  Solvent Effect on Polymorphism in Crystallization of BPT Propyl Ester , 2006 .

[33]  J. Bernstein,et al.  Facts and fictions about polymorphism. , 2015, Chemical Society reviews.

[34]  V. L. Bagirova,et al.  Developing methodological approaches to standardization of pharmaceutical substances , 2010, Pharmaceutical Chemistry Journal.

[35]  Krist V. Gernaey,et al.  A systematic framework for design of process monitoring and control (PAT) systems for crystallization processes , 2013, Comput. Chem. Eng..

[36]  Ali N. Saleemi,et al.  Active Polymorphic Feedback Control of Crystallization Processes Using a Combined Raman and ATR-UV/Vis Spectroscopy Approach , 2014 .

[37]  Narayan Variankaval,et al.  From Form to Function: Crystallization of Active Pharmaceutical Ingredients , 2008 .

[38]  Dimitrios A Lamprou,et al.  Investigation of an 11mm diameter twin screw granulator: Screw element performance and in-line monitoring via image analysis. , 2015, International journal of pharmaceutics.

[39]  Zoltan K. Nagy,et al.  Application of Process Analytical Technology-Based Feedback Control Strategies To Improve Purity and Size Distribution in Biopharmaceutical Crystallization , 2015 .

[40]  Z. Nagy,et al.  Adaptive concentration control of cooling and antisolvent crystallization with laser backscattering measurement , 2009 .

[41]  M. Gligoric,et al.  Modelling the process of Al(OH)3 crystallization from industrial sodium aluminate solutions using artificial neural networks , 2011 .

[42]  N. Urbanetz,et al.  Simultaneous quantitative analysis of ternary mixtures of D-mannitol polymorphs by FT-Raman spectroscopy and multivariate calibration models. , 2010, International journal of pharmaceutics.

[43]  J. Bernstein.  Polymorphism − A Perspective , 2011 .

[44]  Zoltan K. Nagy,et al.  Raman, UV, NIR, and Mid‐IR Spectroscopy with Focused Beam Reflectance Measurement in Monitoring Polymorphic Transformations , 2014 .

[45]  Joachim Ulrich,et al.  Data Preprocessing of In Situ Laser‐Backscattering Measurements , 2011 .

[46]  Martha A. Grover,et al.  Using MC plots for control of paracetamol crystallization , 2017 .

[47]  S. Katz,et al.  Some problems in particle technology: A statistical mechanical formulation , 1964 .

[48]  Z. Nagy,et al.  A link between the ATR-UV/Vis and Raman spectra of zwitterionic solutions and the polymorphic outcome in cooling crystallization , 2015 .

[49]  Z. Nagy,et al.  Novel semibatch supersaturation control approach for the cooling crystallization of heat‐sensitive materials , 2020 .

[50]  M. Bernard,et al.  IDENTIFICATION OF DABIGATRAN ETEXILATE MAJOR DEGRADATION PATHWAYS BY LIQUID CHROMATOGRAPHY COUPLED TO MULTI STAGE HIGH-RESOLUTION MASS SPECTROMETRY , 2015 .

[51]  Zoltan K. Nagy,et al.  ON–OFF Feedback Control of Plug-Flow Crystallization: A Case of Quality-by-Control in Continuous Manufacturing , 2017, IEEE Life Sciences Letters.

[52]  Richard D. Braatz,et al.  First-principles and direct design approaches for the control of pharmaceutical crystallization , 2005 .

[53]  B. Glennon,et al.  Novel, Calibration-Free Strategies for Supersaturation Control in Antisolvent Crystallization Processes , 2013 .

[54]  Nicholas C. S. Kee,et al.  Selective Crystallization of the Metastable Anhydrate Form in the Enantiotropic Pseudo-Dimorph System of l-Phenylalanine using Concentration Feedback Control , 2009 .

[55]  Xun Tang,et al.  Control of Self-Assembly with Dynamic Programming , 2019, IFAC-PapersOnLine.

[56]  Andrea R. Browning,et al.  Crystal Shape Engineering , 2008 .

[57]  Zoltan K. Nagy,et al.  A Process Analytical Technology Based Investigation of the Polymorphic Transformations during the Antisolvent Crystallization of Sodium Benzoate from IPA/Water Mixture , 2009 .

[58]  H. Pataki,et al.  Implementation of Raman Signal Feedback to Perform Controlled Crystallization of Carvedilol , 2013 .

[59]  Ali N. Saleemi,et al.  In Situ Monitoring of Polymorphic Transformations Using a Composite Sensor Array of Raman, NIR, and ATR-UV/vis Spectroscopy, FBRM, and PVM for an Intelligent Decision Support System , 2015 .

[60]  Z. Nagy,et al.  Systematic design of supersaturation controlled crystallization processes for shaping the crystal size distribution , 2012 .

[61]  Manfred Morari,et al.  Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. III. Wet Milling , 2019, Crystal Growth & Design.

[62]  Leyla Özkan,et al.  In-Process Monitoring and Control of Supersaturation in Seeded Batch Cooling Crystallisation of l-Glutamic Acid: From Laboratory to Industrial Pilot Plant , 2011 .

[63]  Allan S. Myerson,et al.  Control of Polymorphism in Continuous Crystallization via Mixed Suspension Mixed Product Removal Systems Cascade Design , 2015 .

[64]  Julian Morris,et al.  Process analytical technologies and real time process control a review of some spectroscopic issues and challenges , 2011 .

[65]  Ali N. Saleemi,et al.  Comparative Investigation of Supersaturation and Automated Direct Nucleation Control of Crystal Size Distributions using ATR-UV/vis Spectroscopy and FBRM , 2012 .

[66]  V. Liotta,et al.  Monitoring and Feedback Control of Supersaturation Using ATR-FTIR to Produce an Active Pharmaceutical Ingredient of a Desired Crystal Size , 2004 .

[67]  H. Qu,et al.  Polymorphic Control and Scale-up Strategy for Crystallization from a Ternary Antisolvent System by Supersaturation Control , 2020 .

[68]  Ali N. Saleemi,et al.  Automated direct nucleation control for in situ dynamic fines removal in batch cooling crystallization , 2012 .

[69]  Veit Hagenmeyer,et al.  Cascaded two-degree-of-freedom control of seeded batch crystallisations based on explicit system inversion , 2010 .

[70]  Martha A. Grover,et al.  Mass–count plots for crystal size control , 2015 .

[71]  Lie-Jin Guo,et al.  [Study of the phase transformation of TiO2 with in-situ XRD in different gas]. , 2011, Guang pu xue yu guang pu fen xi = Guang pu.

[72]  S. Abbas,et al.  Validated stability indicating methods for determination of nitazoxanide in presence of its degradation products* , 2011, Journal of pharmaceutical analysis.

[73]  F. Puel,et al.  Polymorphism in Processes of Crystallization in Solution: A Practical Review , 2009 .

[74]  Manfred Morari,et al.  Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. I. Concepts and Simulation Studies , 2018, Crystal Growth & Design.

[75]  Manfred Morari,et al.  Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. II. Cooling Crystallization Experiments , 2018, Crystal Growth & Design.

[76]  H. Qu,et al.  Polymorphic Control and Scale-Up Strategy for Antisolvent Crystallization Using a Sequential Supersaturation and Direct Nucleation Control Approach , 2020 .

[77]  Nima Yazdanpanah,et al.  Mechanisms and Control of Impurities in Continuous Crystallization: A Review , 2018, Industrial & Engineering Chemistry Research.

[78]  Juan I. Gómez – Peralta,et al.  Discovering new perovskites with artificial intelligence , 2020 .

[79]  George Zhou,et al.  Process Development and Control with Recent New FBRM, PVM, and IR , 2015 .

[80]  Yu. V. Olefir,et al.  Pharmacopoeial Quality Requirements for Medicinal Products , 2019, Pharmaceutical Chemistry Journal.

[81]  Zoltan K. Nagy,et al.  Prediction and control of crystal shape distribution in the presence of crystal growth modifiers , 2013 .

[82]  Ali N. Saleemi,et al.  Enhancing crystalline properties of a cardiovascular active pharmaceutical ingredient using a process analytical technology based crystallization feedback control strategy. , 2012, International journal of pharmaceutics.

[83]  Haitao Li,et al.  An Integrated Process Analytical Technology (PAT) Approach for Pharmaceutical Crystallization Process Understanding to Ensure Product Quality and Safety: FDA Scientist’s Perspective , 2015 .

[84]  Zoltan K. Nagy,et al.  Recent advances in the monitoring, modelling and control of crystallization systems , 2013 .

[85]  Gürkan Sin,et al.  Comprehensive evaluation of a data driven control strategy: Experimental application to a pharmaceutical crystallization process , 2020, Chemical Engineering Research and Design.

[86]  Z. Nagy,et al.  Comparative performance of concentration and temperature controlled batch crystallizations , 2008 .

[87]  W. Curatolo,et al.  Drug polymorphism and dosage form design: a practical perspective. , 2004, Advanced drug delivery reviews.

[88]  Zoltan K. Nagy,et al.  Real-time feasible model-based crystal size and shape control of crystallization processes , 2019, Computer Aided Chemical Engineering.

[89]  L. L. Simon,et al.  Crystallization process monitoring and control using process analytical technology , 2018 .

[90]  Yang Yang,et al.  Application of feedback control and in situ milling to improve particle size and shape in the crystallization of a slow growing needle-like active pharmaceutical ingredient. , 2017, International journal of pharmaceutics.

[91]  Kristóf Csorba,et al.  Videometric Mass Flow Control: A New Method for Real-Time Measurement and Feedback Control of Powder Micro-Feeding based on Image Analysis. , 2020, International journal of pharmaceutics.

[92]  Michel Benne,et al.  Nonlinear predictive control based on artificial neural network model for industrial crystallization , 2010 .

[93]  S. Veintemillas-Verdaguer.  Chemical aspects of the effect of impurities in crystal growth , 1996 .

[94]  Youngjo Kim,et al.  Optimal feedback control of batch self-assembly processes using dynamic programming , 2020 .

[95]  R. Braatz,et al.  Integrated batch‐to‐batch and nonlinear model predictive control for polymorphic transformation in pharmaceutical crystallization , 2011 .

[96]  Kee-Kahb Koo,et al.  Application of Internal Seeding and Temperature Cycling for Reduction of Liquid Inclusion in the Crystallization of RDX , 2011 .

[97]  Daniel J. Griffin,et al.  Data-Driven Modeling and Dynamic Programming Applied to Batch Cooling Crystallization , 2016 .

[98]  Yang-Hui Luo,et al.  Monitoring the Crystallization Process of Methylprednisolone Hemisuccinate (MPHS) from Ethanol Solution by Combined ATR-FTIR- FBRM- PVM , 2013 .

[99]  Jean-Pierre Corriou,et al.  A new look at optimal control of a batch crystallizer , 2008 .

[100]  Y. Agrawal,et al.  Development of forced degradation and stability indicating studies of drugs—A review , 2013, Journal of pharmaceutical analysis.

[101]  Zoltan K. Nagy,et al.  Application of quantitative Raman spectroscopy for the monitoring of polymorphic transformation in crystallization processes using a good calibration practice procedure , 2014 .

[102]  Richard D. Braatz,et al.  Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review , 2015 .

[103]  Sohrab Rohani,et al.  Recent Developments in the Crystallization Process: Toward the Pharmaceutical Industry , 2017 .

[104]  Kai Sundmacher,et al.  Face-Specific Growth and Dissolution Kinetics of Potassium Dihydrogen Phosphate Crystals from Batch Crystallization Experiments , 2015 .

[105]  R. Braatz,et al.  Selective Crystallization of the Metastable α-Form of l-Glutamic Acid using Concentration Feedback Control , 2009 .

[106]  H. Pataki,et al.  Polymorphic Concentration Control for Crystallization Using Raman and Attenuated Total Reflectance Ultraviolet Visible Spectroscopy , 2020 .

[107]  Zoltan K. Nagy,et al.  Systematic model identification and optimization-based active polymorphic control of crystallization processes , 2017 .

[108]  Alessandro D’Ausilio,et al.  Arduino: A low-cost multipurpose lab equipment , 2011, Behavior Research Methods.

[109]  S. Black,et al.  Investigation into the Cooling Crystallization and Transformations of Carbamazepine Using in Situ FBRM and PVM , 2013 .

[110]  Botond Szilágyi,et al.  Aspect Ratio Distribution and Chord Length Distribution Driven Modeling of Crystallization of Two-Dimensional Crystals for Real-Time Model-Based Applications , 2018, Crystal Growth & Design.

[111]  Yasuaki Yabuki,et al.  Constant Supersaturation Control of Antisolvent-Addition Batch Crystallization , 2006 .

[112]  P. Kleinebudde,et al.  Granule size distributions after twin-screw granulation - Do not forget the feeding systems. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[113]  Chao Y. Ma,et al.  Model identification of crystal facet growth kinetics in morphological population balance modeling of l-glutamic acid crystallization and experimental validation , 2012 .

[114]  S. Reinikainen,et al.  Closed‐Loop Control of Reactive Crystallization. Part I: Supersaturation‐Controlled Crystallization of L‐Glutamic Acid , 2010 .

[115]  Zoltan K. Nagy,et al.  Multi-impurity adsorption model for modeling crystal purity and shape evolution during crystallization processes in impure media , 2016 .