Liquid antisolvent precipitation and stabilization of nanoparticles of poorly water soluble drugs in aqueous suspensions: Recent developments and future perspective

Industrial crystallization from solution

The academic literature on and industrial practice of control of solution crystallization processes have seen major advances in the past 15 years that have been enabled by progress in in-situ real-time sensor technologies and driven primarily by needs in the pharmaceutical industry for improved and more consistent quality of drug crystals. These advances include the accurate measurement of solution concentrations and crystal characteristics as well as the first-principles modeling and robust model-based and model-free feedback control of crystal size and polymorphic identity. Research opportunities are described in model-free controller design, new crystallizer designs with enhanced control of crystal size distribution, strategies for the robust control of crystal shape, and interconnected crystallization systems for multicomponent crystallization.

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Advances and new directions in crystallization control

Crystallization is one of the most important unit operations used for the separation and purification of crystalline solid products. Appropriate design and control of the crystallization process is paramount to produce crystalline products with tailor-made-properties. This paper provides an overview of selected recent developments in the modelling, monitoring and control of crystallization processes. We consider the topics discussed in this review to be enabling technologies for the development of the next generation of crystallization processes with significantly improved predictability, robustness and controllability.

Recent advances in the monitoring, modelling and control of crystallization systems

Interest in the interaction of acoustic waves with particulate mixtures has a long history—dating back to the work of Rayleigh in the 19th century. This interest has intensified over the last fifteen years as advances in electronics and instrumentation science have brought the possibility of using ultrasound to characterize colloidal mixtures both in the laboratory and in-process, and in both of these contexts a small number of instruments are currently in use. The characterization of colloidal mixtures by ultrasound requires a formal theoretical basis which relates the properties of the mixture, particularly the dispersed phase particle size distribution (PSD), to the complex wavenumber governing propagation. The number of theoretical treatments is vast, having evolved over more than a century. This paper is intended to provide a review of these developments in a form which will enable new researchers in the field to climb a very steep learning curve in a relatively short time. We discuss definitions and production techniques for colloidal mixtures and the basic physical phenomena underlying wave propagation through them. We identify two approaches to the propagation problem—scattering and coupled-phase; these are treated both separately and comparatively, particularly in relation to limitations that arise when the concentration of particles is high and the basic theories break down. We introduce the basic method for the measurement of PSD and show how dynamic effects such as flocculation and crystallization can be observed and modelled. The core of all ultrasonic characterization procedures is the physical measurement of the ultrasonic wave attenuation coefficient and phase velocity as functions of frequency; here we discuss these techniques on the basis that what is observable or measurable about a colloid depends on both its physical properties and the frequency bandwidth available for measurement. This paper concludes with our view on future developments of measurement technique and theoretical treatments.

https://iopscience.iop.org/article/10.1088/0034-4885/68/7/R01/pdf

J.W. Mullin

Papers

Programmed cooling of batch crystallizers