Industrial Crystallization and Precipitation From Solutions: State of the Technique

Abstract

Crystallization and precipitation from solutions are responsible for 70% of all solid materials produced by the chemical industry. Competing with distillation as a separation and purification technique, their use is widespread. They operate at low temperatures with low energy consumption and yield with high purifications in one single step. Operational conditions largely determine product quality in terms of purity, filterability, flowability and reactivity. Producing a material with the desired quality often requires a sound knowledge of the elementary steps involved in the process: creation of supersaturation, nucleation, crystal growth, aggregation and other secondary processes. Mathematical models coupling these elementary processes to all particles in a crystallizer have been developed to design and optimize crystallizer operation. For precipitation, the spatial distribution of reactants and particles in the reactor is important; thus the tools of computational fluid dynamics are becoming increasingly important. For crystallization of organic chemicals, where incorporation of impurities and crystal shape are critical, molecular modeling has recently appeared as a useful tool. These theoretical developments must be coupled to experimental data specific to each material. Theories and experimental techniques of industrial crystallization and precipitation from solutions are reviewed, and recent developments are highlighted

Controlling Polymorphism in Pharmaceutical Compounds Using Solution Shearing

“…Temperature has been shown to be a fundamental parameter in directing polymorph formation both in bulk and thin films, as it directly influences the supersaturation. [24][25] Control of solute concentration is another parameter that is traditionally important to industrial crystallization; phase stability can be linked to crystallization from specific solute concentrations. 26 Since nucleation requires aggregation of precursors to achieve a critical effective size, using a low concentration can limit interactions and increase induction time required for nucleation (and decrease the number of nucleation events due to decreased supersaturation), allowing a growth dominant regime to occur.…”

Real-Time Analysis to Evaluate Crystallization Processes

“…The solubility or condition of saturation is determined experimentally by heating a suspension and observing the temperature at which the solid phase is completely dissolved. The cooling of a saturated solution results in a system that is not in thermodynamic equilibrium, a supersaturated solution (Mullin, 2001;Giulietti et al, 2001). …”

“…The usage of this method is restricted to substances whose solubility changes significantly during a temperature variation. The expected properties of the solid material, as well as economic aspects, form the basis for making a decision about which method should be used to create supersaturation (Mullin, 2001;Giulietti et al, 2001).…”

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

“…On the other hand, these characteristics also provide the opportunity to control the drug release profile after intake into the human body. As a result, industrial processes exploit numerous particle engineering techniques in combination with crystallization to produce crystals that meet both the bioavailability and processing requirements [1][2][3][4][5][6].…”