Large crystals of sodium chloride – macro. Copyright: pzAxe@Shutterstock

Nowadays, single enantiomeric chiral active pharmaceutical ingredients dominate among new drugs. Direct methods for the separation of racemates simplify their preparation. A survey is given on the history of this topic as well as information about actual methods of conglomerate identification and practical implementation options for direct resolutions.

Calcium propionate is frequently used as food additive. Basic studies on its solubility and solid-state forms in water and ethanol-water mixtures as well as thermal behavior were performed. The results obtained provide a better understanding of thermal and solubility behavior of calcium propionate and serve as base to improve its crystallization process in the future.

Needle-shaped monosodium urate monohydrate (MSU) crystals deposited in synovial fluid provoke the acute inflammatory response of gout. The crystallization mechanism of MSU was investigated. Stirring helped to crystallize MSU faster and larger in amount. A high urate concentration enhanced the nucleation of MSU. The results promote the importance of serum urate level control as gout treatment.

Slurry experiments are common to assess the required amount of water in order to ensure or avoid hydrates in crystallization. The stability of anhydrate and monohydrate I of sodium dehydroacetate was measured at different solvent compositions and temperatures and a new monohydrate II was detected. Explanations for the formation of different sodium dehydroacetate forms are proposed.

A fast and simple method for synthesizing Pt nanoparticles is required. Monodispersed Pt nanoparticles were successfully synthesized by reductive crystallization using polyethyleneimine as a protective reagent and NaBH₄ as a reducing agent. Size and morphology of the Pt nanoparticles were controlled by changing the pH of the reaction field.

An alternative packaging for milk or condensed milk as an innovative and unique alternative to common plastic jars is introduced. A method is developed to encapsulate milk or condensed milk by means of crystallization. Successful encapsulation is demonstrated creating capsules with a hard and stable crust. Sucrose and erythritol are used to form a crystalline layer.

A racemic suspension of conglomerate-forming species can be converted to a homochiral suspension in a fast racemizing solution by temperature cycle-induced deracemization. This process is modeled using the population balance model for the two enantiomorphs, applying the program gCrystal to obtain an accurate simulation of the evolution of the enantiomeric excess in the crystal phase.

The analysis of gelatin, agar, or carrageenans in crystallized sucrose is an important method to estimate the effects of hydrocolloids on crystallized coated products. An incorporation of these texturants can lead to product changes like storage stability, layer thicknesses, and mouth feeling. All hydrocolloids are incorporated into the coating material during layer formation of coated sweets.

Chiral lactide is a model substance to study the solution thermodynamics of a chiral racemic compound-forming system. The solution enthalpy is considered to consist of three thermodynamic steps: melting of the crystal, transition of the subcooled melt to an infinite dilution, and the subsequent transition to a saturated solution. This model is an alternative way to obtain the solution enthalpy from measured solubilities.

Hollow sodium chloride crystals are considered as potential high-value-added crystals. Such crystals were successfully synthesized by dropping an aqueous sodium chloride solution into a mixed solvent of cyclohexane and acetone and characterized by X-ray diffraction and optical microscopic imaging. Possible growth mechanisms were proposed to elucidate the formation of the obtained crystals.

The design and optimization of robust crystal-habit-modification procedures can improve the solid-state properties of an active pharmaceutical ingredient (API). A toolbox of techniques is available to develop or optimize crystallization processes in light of the crystal shape, thereby enabling more efficient processing and subsequent formulation.

Phosphorus recovered from reject water from a wastewater treatment plant can be used as a phosphate fertilizer. The composition of the wastewater affects the quality of the product, so the effects of solution composition and polymer additive on the crystallization of struvite have been studied. Controlling the crystallization process guarantees the consistent production of struvite with desired properties.

The effects of sonication in the three defined stages of cooling crystallization of paracetamol were evaluated. Tuning of the ultrasonic power density and the exposure time after nucleation resulted in varying crystal sizes, whereas the use of ultrasound before nucleation did not affect the particle size distribution, pointing at enhanced secondary nucleation as the main mechanism.

Drowning-out crystallization allows effective control of polymorphism and particle sizes. 2,4,6,8,10-Hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane is used as a model compound to determine laboratory-scale conditions of crystallization for scaling up. The polymorphic β and ε forms were selected by controlling supersaturation and the ratio of components in the solvent mixture.

Amino acids are widely utilized as medical raw materials and food additives. Since most of the amino acids exhibit polymorphism, polymorph control is essential in crystallization processes. Polymorph control of L-ArgHCl was achieved by ultrasonic irradiation. Its unstable form was selectively crystallized by ultrasonic irradiation. Irradiation caused a shortening of the induction time.

The impinging jet crystallization method was applied for the first time together with different concentrations of potassium chloride as an additive in order to modify the crystal habit of glycine particles. Relevant factors affecting the impinging jet-crystallized product were identified by a 3² full factorial design, revealing the additive concentration and the post-mixing time as important process parameters.

The KCl-KH₂PO₄-C₂H₅OH-H₂O system is relevant to process design for the crystallization of KH₂PO₄. Hence, its solid-liquid phase equilibrium, solubility data, and physicochemical properties were determined at 313.15 K. Drowning-out precipitation of KH₂PO₄ was carried out in order to observe the crystal morphology, and the effect of KCl on KH₂PO₄ crystallization was investigated.

Liquid-liquid phase separation, also termed oiling-out, means a challenge for crystallization processes which is largely unwanted. The influence of oiling-out on crystal properties for a mixture of L-menthol in water was investigated. Solvent inclusions were detected within the L-menthol crystals. Oiling-out crystallization conditions were found to affect the amount of such inclusions.

A strategy for analysis of advanced photocatalysts in wastewater treatment is proposed. Electrons are excited from the valence band to the conduction band to form photogenerated electrons, leaving holes in the valence band. Such electrons are transferred to the surface of graphene which reduces the recombination rate of photogenerated electrons and holes and improves the photocatalytic efficiency.

The role of carboxylic acids used as additives in gypsum crystallization is still not clearly clarified. Combined analyses proved that the amount of carboxylic acid adsorbed onto the calcium sulfate dihydrate crystals increased with higher carbonyl group numbers. This affected significantly the morphology, particle size, and filtration characteristics of the calcium sulfate dihydrate crystals.

Some aspects like process modeling, monitoring, and control problems in continuous mixed-solution mixed-product removal crystallization are still challenging. An innovative approach for online measurement of the crystal size distribution is proposed. Discrepancy-based control is designed and applied to a nonlinear model taking system nonlinearities into account.

Phase-contrast magnetic resonance imaging (PC-MRI) applied on rotating systems is highly challenging since a non-ferromagnetic system has to be developed before. The complex 3D unsteady flow in a stirred tank representing a rotating batch crystallizer is considered. The hydrodynamics in space and time could be noninvasively quantified using flow-sensitive PC-MRI.