Attrition-enhanced deracemization of NaClO3 : comparison between ultrasonic and abrasive grinding

Ultrasound-enhanced grinding is a more practical alternative to glass bead-enhanced grinding for performing attrition-enhanced deracemization at large scale or in continuous flow. In this work, both ultrasound-enhanced grinding (41.2 kHz) and glass bead-enhanced grinding were applied to induce Viedma deracemization of sodium chlorate (NaClO3) crystals in isothermal conditions. The results demonstrate that high intensity, low frequency ultrasound can achieve efficient grinding of enantiomorphous NaClO3 crystals, producing small crystal size and narrow size distribution, both being highly desirable final product properties. Monitoring the width of the crystal size distribution reveals its crucial role and offers further insight into the underlying phenomena in the deracemization process. Compared to glass bead-enhanced grinding, ultrasound-enhanced grinding resulted in faster crystal size reduction and rapid initial deracemization. However, a further increase in the enantiomeric excess was hindered after prolonged times of ultrasonication. This ensues probably due to the absence of crystal size-induced solubility gradients, owing to the existence of close to monodispersed sized crystals after the initial stage in the ultrasound-enhanced grinding process. We show that this can be overcome by combining (a) ultrasound with glass beads or (b) ultrasound with seeding, both of which led to enantiopurity

Restless legs syndrome/Willis–Ekbom disease prevalence in beta thalassemia patients

Purpose Both beta thalassemia and restless legs syndrome (RLS) patients share some common pathophysiological characteristics related to iron handling. In the present study, the aim was to explore the prevalence of RLS as well as to explore potential association between the syndrome and various quality of life-related parameters in a sample of beta thalassemia patients. Methods One hundred fourteen (age 40 ± 11 yr, 59 M/55F) beta thalassemia patients participated in this cross-sectional descriptive study. Patients were screened for RLS based on the international RLS study group diagnostic criteria as well as a battery of validated questionnaires. Results The prevalence of RLS in this sample of beta thalassemia patients was zero. The quality of life score was low (78 ± 18). Iron levels were within normal range (191 ± 66 mcg/dL) while ferritin levels were high as expected (1836 ± 225 ng/dL). Conclusions Our sample of patients comes from central Greece where the prevalence of RLS in the general population is 4% while in renal failure patients is 27%. To our surprise, there was no presence of RLS among this sample of beta thalassemia patients. The adequate levels of iron and ferritin often seen in these patients could be the reason of the absence of RLS symptoms

Subtle Microwave-Induced Overheating Effects in an Industrial Demethylation Reaction and Their Direct Use in the Development of an Innovative Microwave Reactor

A systematic study of the conventional and microwave (MW) kinetics of an industrially relevant demethylation reaction is presented. In using industrially relevant reaction conditions the dominant influence of the solvent on the MW energy dissipation is avoided. Below the boiling point, the effect of MWs on the activation energy Ea and k0 is found nonexistent. Interestingly, under reflux conditions, the microwave-heated (MWH) reaction displays very pronounced zero-order kinetics, displaying a much higher reaction rate than observed for the conventionally thermal-heated (CTH) reaction. This is related to a different gas product (methyl bromide, MeBr) removal mechanism, changing from classic nucleation into gaseous bubbles to a facilitated removal through escaping gases/vapors. Additionally, the use of MWs compensates better for the strong heat losses in this reaction, associated with the boiling of HBr/water and the loss of MeBr, than under CTH. Through modeling, MWH was shown to occur inhomogeneously around gas/liquid interfaces, resulting in localized overheating in the very near vicinity of the bubbles, overall increasing the average heating rate in the bubble vicinity vis-à-vis the bulk of the liquid. Based on these observations and findings, a novel continuous reactor concept is proposed in which the escaping MeBr and the generated HBr/water vapors are the main driving forces for circulation. This reactor concept is generic in that it offers a viable and low cost option for the use of very strong acids and the managed removal/quenching of gaseous byproducts

Coupling Viedma ripening with racemic crystal transformations : mechanism of deracemization

It has been recently observed that coupling Viedma ripening with a seeded in situ metastable racemic crystal to conglomerate transformation leads to accelerated and complete deracemization: crystal transformation-enhanced deracemization. By means of a simple kinetic model, we show that the mechanistic pathway of this new process depends profoundly on the interplay between the crystal transformation and racemization processes, which in turn influence the nucleation process of the counter enantiomer. If the nucleation of the counter enantiomer is suppressed (e.g., by sufficiently fast racemization, low amount of racemic compound or gradual feed, low relative solubility between racemic compound and conglomerate), deracemization proceeds via a second order asymmetric transformation (SOAT) and is limited primarily by the dissolution rate of the racemic crystals and the growth rate of the preferred enantiomer crystals. Breakage and agglomeration accelerate the process, but contrary to conventional Viedma ripening, they are not essential ingredients to explain the observed enantiomeric enrichment. If the nucleation process of the counter enantiomer is not sufficiently suppressed, deracemization is initially controlled by the dissolution rate of the racemic crystals, but Viedma ripening is subsequently required to convert the conglomerate crystals of the counter enantiomer formed by nucleation, resulting in slower deracemization kinetics. In both cases, the combined process leads to faster deracemization kinetics compared to conventional Viedma ripening, while it autocorrects for the main disadvantage of SOAT, i.e., the accidental nucleation of the counter enantiomer. In addition, crystal transformation-enhanced deracemization extends the range of applicability of solid-state deracemization processes to compounds that form metastable racemic crystals

Immobilization of gluten in spherical matrices of food-grade hydrogels

The aim of this paper is to produce spherical encapsulates of wheat gluten in a food-grade biopolymer for preparing sheared meat analogs, to prevent instant fibrilization of the gluten during a pre-mixing step. The hydrogel should release the gluten inside the Couette Cell, as a result of the higher temperature and shear in the process. Both sodium alginate and κ-carrageenan were used as encapsulants. Spherical particles of hydrogel-gluten mixtures were produced by means of a dripping method using an encapsulator. While the particle properties of κ-carrageenan surpassed those of alginate in terms of controlled release of the core, the particle production using the encapsulator was more complicated. With κ-carrageenan, a layer of oil on top of the cross-linking bath fluid, as well as through the outer orifice of a concentric nozzle were required to obtain a good sphericity of the particles. For the alginate particles the use of oil was not necessary. Gluten loadings of 7% w/w were achieved with 1.5% w/w alginate and with 2% w/w κ-carrageenan. The water content of the particles can be easily controlled by a subsequent partial drying step. A mixture of Soy Protein Isolate and particles was sheared in the Couette Cell. Controlled release of the gluten from the alginate particles was not achieved properly by temperature or shear. The controlled release of the gluten was achieved at the processing conditions only with κ-carrageenan. Some fibrilization was observed in the sheared product, but the macrostructure was not yet well developed. However, an optimization of the shearing process for the use of the particles may lead to an improved structure for the meat analogs. Practical applications: This paper investigated the effect of encapsulation in hydrogels on the fibrilization behavior of wheat gluten upon contact with water. A cheap and easily scalable dripping technique was used to create spherical particles in which the gluten did not fibrilize, although the coating material consists of ≥95% of water. Upon reaching the process conditions in the shearing device, the gluten is released and able to form fibers. The results show that hydrogels can mechanically protect the core and act as a delivery structure. The protective and carrier functions of the hydrogel can alternatively be used for cores like food additives (e.g., vitamins) or even to pharmaceutical ingredients, not only for the production of meat analogs, but also in other food applications

Restless legs syndrome is contributing to fatigue and low quality of life levels in hemodialysis patients

AIM: To examine whether hemodialysis (HD) patients with restless legs syndrome (RLS) are subjects of greater fatigue and impaired quality of life (QoL) compared to HD patients without RLS. METHODS: Eighty five stable HD patients participated in this study. According to their RLS status, the patients were divided into the RLS group (n = 23) and the non-RLS group (n = 62). QoL, fatigue, sleep quality, daily sleepiness and depression symptoms were assessed by using various questionnaires. Finally, biochemical parameters including iron, ferritin, hemoglobin, hematocrit and parathormone were assessed. RESULTS: The HD patients with RLS scored worse in all the questionnaires used in the study (P < 0.05). The patients with RLS were more likely to receive the HD therapy on the morning shift, whilst 43.5% of the RLS patients reported to experience the RLS symptoms also during HD. The severity of RLS was correlated with fatigue, depression score and sleep quality (P < 0.05). CONCLUSION: HD patients with RLS are subject to lower QoL related parameters and greater fatigue compared to HD patients without RLS. RLS should be successfully managed in order to improve the QoL of the sufferers

On the effect of secondary nucleation on deracemization through temperature cycles

Herein, the pivotal role of secondary nucleation in a crystallization-enhanced deracemization process is reported. During this process, complete and rapid deracemization of chiral conglomerate crystals of an isoindolinone is attained through fast microwave-assisted temperature cycling. A parametric study of the main factors that affect the occurrence of secondary nucleation in this process, namely agitation rate, suspension density, and solute supersaturation, confirms that an enhanced stereoselective secondary nucleation rate maximizes the deracemization rate. Analysis of the system during a single temperature cycle showed that, although stereoselective particle production during the crystallization stage leads to enantiomeric enrichment, undesired kinetic dissolution of smaller particles of the preferred enantiomer occurs during the dissolution step. Therefore, secondary nucleation is crucial for the enhancement of deracemization through temperature cycles and as such should be considered in further design and optimization of this process, as well as in other temperature cycling processes commonly applied in particle engineering

Towards deracemization in the absence of grinding through crystal transformation, ripening, and racemization

New insights into the obscure mechanisms of solid-state deracemization phenomena are obtained by crystal ripening experiments that, contrary to standard techniques, exclude attrition enhancement (grinding). The results point out that small particles and an initial size imbalance between the two enantiomeric crystal populations can intensify the rate of solidstate enantiomeric enrichment even in the absence of intermediate actions (e.g., grinding or thermal cycling). On this ground, a new process that creates such initial conditions is designed and exemplified for the proteinogenic glutamic acid. As a first step, racemic compound solvate (DL-glutamic acid monohydrate) crystals are completely converted to small-sized conglomerate anhydrate crystals, in the presence of larger seeds of a single chirality. After the transformation is complete and the racemization catalyst is added, the suspension contains an equal number of small-sized conglomerate crystals of both enantiomers together with the larger seeds of the preferred enantiomer. Over time, the large crystals of the preferred enantiomer tend to grow at the expense of smaller ones, which dissolve. This, combined with the fast racemization, leads to enantiomeric enrichment. The possible occurrence of enantioselective agglomeration between small and seed crystals speeds up this process by removing small crystals of the preferred enantiomer. Since most amino acids and several other pharmaceutical compounds are known to form metastable racemic hydrate crystals, it is expected that this new method is readily applicable to a variety of compounds. In addition, the process provides a technically simpler and more scalable route to enantiomeric enrichment compared to attritionenhanced deracemization, and its applicability extends to the wider pool of compounds that crystallize as racemic crystals

Particle breakage kinetics and mechanisms in attrition-enhanced deracemization

In this study, we report on experiments designed to deconvolute the particle breakage kinetics and mechanism from the parallel phenomena (growth-dissolution, agglomeration) in attrition-enhanced deracemization processes. Through such experiments, we derived the specific breakage rates and cumulative breakage distribution functions for three grinding methods typically used in deracemization experiments: (a) bead grinding, (b) ultrasound grinding, and (c) the combination of bead and ultrasound grinding. Subsequently, we tested these methods on their ability to induce deracemization. We show that in the conventional bead grinding process, breakage occurs mostly by fracture. This results in slow deracemization rates due to the delayed formation of submicron particles that are essential to the process. Conversely, ultrasound grinding very efficiently breaks particles by abrasion. This leads to fast generation of an abundance of submicron fragments resulting in fast deracemization. However, using ultrasound, large crystals fracture rates are an order of magnitude lower than those using bead grinding, which results in an insufficient size decrease of the large counter enantiomer crystals and eventually to incomplete deracemization. Remarkably, the simultaneous application of bead and ultrasound grinding leads, due to synergistic effects of both fracture and abrasion, to 2-fold higher total deracemization rates compared to bead grinding alone. The present work offers new insights into the key role of particle breakage in attrition-enhanced deracemization, together with a basis for decoupling the individual phenomena involved in the process