Precise tailoring of the crystal size distribution by controlled growth and continuous seeding from impinging jet crystallizers

The desired bioavailability and the method of drug administration and delivery can require stringent control on the crystal size distribution. Optimal control strategies are proposed to manufacture crystals with a targeted size distribution by combining controlled seeding by impinging jet crystallization with a batch crystallizer operating at a controlled constant growth rate. The same strategies apply if the impinging jet crystallization is replaced by any process equipment that can continuously provide crystal seeds, typically through the application of high supersaturation, to the batch crystallizer. Limitations to the achievable crystal size distributions and sensitivity to process operations are analyzed. Simulation results indicate that one of the strategies has promise for manufacturing pharmaceutical crystals of a desired size distribution.

[1]  Kevin Girard,et al.  Control of the Particle Properties of a Drug Substance by Crystallization Engineering and the Effect on Drug Product Formulation , 2005 .

[2]  M. Mazzotti,et al.  Gas antisolvent recrystallization of an organic compound. Tailoring product PSD and scaling-up , 2003 .

[3]  Robert K. Prud'homme,et al.  Flash NanoPrecipitation of Organic Actives and Block Copolymers using a Confined Impinging Jets Mixer , 2003 .

[4]  Robin Smith,et al.  Optimization of batch cooling crystallization , 2004 .

[5]  D. L. Ma,et al.  Optimal seeding in batch crystallization , 1999 .

[6]  D. L. Ma,et al.  Optimal control and simulation of multidimensional crystallization processes , 2002 .

[7]  Edward L. Paul,et al.  Organic crystallization processes , 2005 .

[8]  E. Tadmor,et al.  New High-Resolution Central Schemes for Nonlinear Conservation Laws and Convection—Diffusion Equations , 2000 .

[9]  Pedro M. Saraiva,et al.  Chemical product engineering: An emerging paradigm within chemical engineering , 2006 .

[10]  Sohrab Rohani,et al.  Control of Product Quality in Batch Crystallization of Pharmaceuticals and Fine Chemicals. Part 2: External Control , 2005 .

[11]  María José Cocero,et al.  Numerical modeling of jet hydrodynamics, mass transfer, and crystallization kinetics in the supercritical antisolvent (SAS) process , 2004 .

[12]  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 .

[13]  J. W. Mullin,et al.  Programmed cooling crystallization of potassium sulphate solutions , 1974 .

[14]  B. Shekunov,et al.  CRYSTALLIZATION PROCESSES IN PHARMACEUTICAL TECHNOLOGY AND DRUG DELIVERY DESIGN , 2000 .

[15]  R. Braatz,et al.  Parameter Estimation and Optimization of a Loosely Bound Aggregating Pharmaceutical Crystallization Using in Situ Infrared and Laser Backscattering Measurements , 2004 .

[16]  L. Nagao,et al.  Aspects of Particle Science and Regulation in Pharmaceutical Inhalation Drug Products , 2005 .

[17]  N. Kubota,et al.  LARGE AND MONO-SIZED PRODUCT CRYSTALS FROM NATURAL COOLING MODE BATCH CRYSTALLIZER , 1996 .

[18]  A. Mahajan,et al.  Micromixing effects in a two-impinging-jets precipitator , 1996 .

[19]  J. R. Torres-Lapasió,et al.  Automatic program for peak detection and deconvolution of multi-overlapped chromatographic signals part II: peak model and deconvolution algorithms. , 2005, Journal of chromatography. A.

[20]  N. Kubota,et al.  Seeding Effect on Batch Crystallization of Potassium Sulfate under Natural Cooling Mode and a Simple Design Method of Crystallizer , 1999 .

[21]  J. D. Ward,et al.  Choosing an operating policy for seeded batch crystallization , 2006 .

[22]  A. Bauer-Brandl Polymorphic transitions of cimetidine during manufacture of solid dosage forms , 1996 .

[23]  Jennifer Jung,et al.  Particle design using supercritical fluids: Literature and patent survey , 2001 .

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

[25]  C. W. Kim,et al.  A novel insulin microcrystals preparation using a seed zone method , 2004 .

[26]  C. Porte,et al.  Effect of seeded surface area on crystal size distribution in glycine batch cooling crystallization: a seeding methodology , 2004 .

[27]  Richard D. Braatz,et al.  Modelling and control of combined cooling and antisolvent crystallization processes , 2008 .

[28]  S. Rohani,et al.  Control of Product Quality in Batch Crystallization of Pharmaceuticals and Fine Chemicals. Part 1: Design of the Crystallization Process and the Effect of Solvent , 2005 .

[29]  Jerzy Bałdyga,et al.  Particle formation by turbulent mixing with supercritical antisolvent , 2005 .

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

[31]  C. B. Roberts,et al.  High-resolution imaging of the supercritical antisolvent process , 2005 .

[32]  Wolfgang Beckmann,et al.  Seeding the Desired Polymorph: Background, Possibilities, Limitations, and Case Studies , 2000 .

[33]  Noriaki Kubota,et al.  Seeding Effect on Product Crystal Size in Batch Crystallization , 2002 .

[34]  Ruggero Bettini,et al.  Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[35]  Antonello Barresi,et al.  Design and scale‐up of chemical reactors for nanoparticle precipitation , 2006 .

[36]  N. Rasenack,et al.  Micronization of anti-inflammatory drugs for pulmonary delivery by a controlled crystallization process. , 2003, Journal of pharmaceutical sciences.

[37]  E. Süli,et al.  Numerical Solution of Partial Differential Equations , 2014 .

[38]  R. Braatz,et al.  Modeling and Computational Fluid Dynamics−Population Balance Equation−Micromixing Simulation of Impinging Jet Crystallizers , 2009 .

[39]  D. L. Ma,et al.  Optimal model-based experimental design in batch crystallization , 2000 .

[40]  R. Braatz,et al.  Paracetamol Crystallization Using Laser Backscattering and ATR-FTIR Spectroscopy: Metastability, Agglomeration, and Control , 2002 .

[41]  J. R. Torres-Lapasió,et al.  A model for the description, simulation, and deconvolution of skewed chromatographic peaks , 1997 .

[42]  R. Koppmann,et al.  A new mathematical procedure to evaluate peaks in complex chromatograms. , 2005, Journal of chromatography. A.

[43]  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 .

[44]  M. Mazzotti,et al.  Model-Based Optimization of Particle Size Distribution in Batch-Cooling Crystallization of Paracetamol , 2004 .

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

[46]  J. Rawlings,et al.  Model identification and control of solution crystallization processes: a review , 1993 .

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

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

[49]  D. L. Ma,et al.  Robust identification and control of batch processes , 2003, Comput. Chem. Eng..

[50]  D. L. Ma,et al.  IDENTIFICATION OF KINETIC PARAMETERS IN MULTIDIMENSIONAL CRYSTALLIZATION PROCESSES , 2002 .