Crystallization is an important technique for separation and purification of substances as well as for product design in chemical, pharmaceutical and biotechnological process industries. This ready reference and handbook draws on research work and industrial practice of a large group of experts in the various areas of industrial crystallization processes, capturing the essence of current trends, the markets, design tools and technologies in this key field. Along the way, it outlines trouble free production, provides laboratory controls, analyses case studies and discusses new challenges. First the instrumentation and techniques used to measure the crystal size distribution, the nucleation and solubility points, and the chemical composition of the solid and liquid phase are outlined. Then the main techniques adopted to control industrial crystallizers, starting from fundamental approaches to the most advanced ones, including the multivariable predictive control are described. An overview of the main crystallizer types is given with details of the main control schemes adopted in industry as well as the more suitable sensors and actuators.

Crystallization is an important separation and purification process used in industries ranging from bulk commodity chemicals to specialty chemicals and pharmaceuticals. In recent years, a number of environmental applications have also come to rely on crystallization in waste treatment and recycling processes.The authors provide an introduction to the field of newcomers and a reference to those involved in the various aspects of industrial crystallization. It is a complete volume covering all aspects of industrial crystallization, including material related to both fundamentals and applications. This new edition presents detailed material on crystallization of biomolecules, precipitation, impurity-crystal interactions, solubility, and design.Provides an ideal introduction for industrial crystallization newcomers Serves as a worthwhile reference to anyone involved in the fieldCovers all aspects of industrial crystallization in a single, complete volume

An overview of crystallization processes of organic and inorganic substances from various homogeneous liquids. Crystal structures, phase transitions and crystallization rates are described in the book in connection with the structure of ions, complexes and molecules of the solution phase.

Pharmaceutical crystallisation operation is often critical because it determines product properties, such as the crystal size distribution (CSD) and polymorphic form, that can influence the subsequent downstream operations and the product therapeutic performance. Driven by the United States Food and Drug Administration's (FDA) Process Analytical Technology (PAT) initiative and the Quality-by-Design (QbD) concept, the development of control approaches, which can improve the manufacturing of products with desired properties, has become of significant interest. This thesis presents the development and application of PAT-based approaches for the monitoring and control of pharmaceutical crystallisation operations that will ensure consistent production of active pharmaceutical ingredients (APIs) with the desired size and polymorphic form. The approaches utilised Lasentec focused beam reflectance measurement (FBRM) and attenuated total reflectance ultraviolet (ATR-UV) spectroscopy as the in situ monitoring and control tools. Crystallisations of the APIs that posses multiple polymorphs are both critical and challenging. This was illustrated in this work by the crystallisations of sulfathiazole polymorphs using literature methods. The processes were monitored using FBRM and ATR-UV spectroscopy to define the design range of the process parameters. The defined range could be used as a recipe to reproduce the same quality of crystals. The obtained crystals were characterised using various techniques (optical microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry, hot-stage microscopy (HSM), Fourier Transform infrared spectroscopy and powder X-ray diffractometry) to assess the success of the crystallisation processes. The combined results of the techniques showed that all methods were able to produce the desired pure polymorphs. As a contribution to the technique of investigating polymorphism, a combined approach of DSC-HSM with image analysis, was introduced. Results show the capability of the approach to provide a unique insight into the polymorphic transformations and thermal behaviour exhibited by the model compound. The novel direct nucleation control (DNC) approach was introduced to control the CSD. The approach utilises information on nucleation, provided by FBRM, in a feedback control strategy that adapts the process variables, so that the desired CSD of product is achieved. It also provides in situ fines removal through the operating policy, rather than having additional equipment and external recycle loops. The approach does not require concentration measurement and has the advantage of being a model-free approach, requiring no information on nucleation or growth kinetics in order to design an operating curve; the system automatically and adaptively detects the boundary of the operating curve. Experimental results, using glycine in water-ethanol mixture as a model system, show the benefits of DNC to produce larger crystals with narrower CSD compared to uncontrolled operations. The capability of seeded cooling crystallization with temperature cycling approach to control crystal size uniformity and polymorphic purity was evaluated. Using sulfathiazole in n-propanol and in water as model systems, the method was found to accelerate the growth and enhance the size uniformity of the crystals, in comparison with runs using a linear temperature profile, by promoting Ostwald ripening. Although the approach is conceptually capable of controlling polymorphic purity of a system, the effect of solvent-mediated nucleation/growth can be more dominant, as shown by the results of the experiments. The insights into this behaviour of sulfathiazole crystals were captured very well by the FBRM. The study also demonstrated the successful use of a simple non-linear function as a calibration model to relate temperature and absorbance data, obtained using the ATR-UV spectroscopy, to solute concentration during the crystallisation process. The effect of temperature cycling, performed during seeded cooling crystallisation, on the surface features of sulfathiazole crystals was investigated using FBRM and ex situ optical microscopy, SEM and atomic force microscopy. It was observed during the initial stage of the process, the heating phases produced crystals with smooth surfaces, whilst the cooling phases promoted growth of features on the surfaces. These changes detected by the FBRM as an increase in the number of coarse counts during heating and a drop during cooling. Laser beam spreading caused by the surface roughness, and signal/chord splitting due to sharp edges are offered as an explanation for the FBRM results. This shows the capability of the FBRM to provide useful information about the changes on the surface of the crystalline products. The information can be used to avoid problems in the downstream operations, or in the final product property due to variations in flowability and friability, which are influenced by the surface property.

First published in 1997. Routledge is an imprint of Taylor & Francis, an informa company.

Continuous crystallization is an area of intense research, with particular respect to the pharmaceutical industry and fine chemicals. Improvements in continuous crystallization technologies offer chemical industries significant financial gains, through reduced expenditure and operational costs, and consistent product quality. Written by well-known leaders in the field, The Handbook of Continuous Crystallization presents fundamental and applied knowledge, with attention paid to application and scaling up, and the burgeoning area of process intensification. Beginning with concepts around crystallization techniques and control strategies, the reader will learn about experimental methods and computational tools. Case studies spanning fine and bulk chemicals, the pharmaceutical industry, and employing new mathematical tools, put theory into context.

"Micro-Raman Spectroscopy introduces readers to the theory and application of Raman microscopy. Raman microscopy is used to study the chemical signature of samples with little preparation in a non-destructive manner. An easy to use technique with ever increasing technological advances, Micro-Raman has significant application for researchers in the fields of materials science, medicine, pharmaceuticals, and chemistry."--