<p>Spherical agglomerates of benzoic acid crystals have been successfully prepared by drowning-out crystallization in three solvent partial miscible mixtures. Benzoic acid is dissolved in ethanol, bridging liquid is added and this mixture is fed to the agitated crystallizer containing water. Fine crystals are produced by crystallization of the substance, and the crystals are agglomerated by introduction of an immiscible liquid called the bridging liquid. The concentration of solute, agitation rate, feeding rate, amount of bridging liquid and temperature are found to have a significant influence on the physico-mechanical properties of the product. The product particle characterization includes the particle size distribution, morphology and mechanical strength.</p><p>Many of the solvents such as chloroform, toluene, pentane, heptane, cyclo hexane, diethyl ether and ethyl acetate were used as bridging liquids. Among the selected solvents ethyl acetate and di ethyl ether could not form the spherical agglomerates. Characteristics of the particles are changing with the bridging liquid used. Range of the operation for spherical agglomeration is very narrow and was shown that only at certain conditions the spherical agglomerates are produced. Increased amount of bridging liquid, decrease in feeding rate and temperature causes the particle size to increase. Particle morphology depends on the bridging liquid used, amount of bridging liquid and the temperature. Particles look completely spherical from the experiments where toluene is used as bridging liquid. </p><p>The mechanical strength of single agglomerates has been determined by compression in a materials testing machine, using a 10N load cell. For single particle compression an approximate estimation of the true stress is presented. Compression characteristics for single agglomerates are compared with data on particle bed compression. Low elastic recovery and high compressibility of the single particles and of bed of particles reveals that the spherical agglomerates prepared in this work have a plastic behavior which is expected to be favorable for direct tabletting. Some of the stress–strain curves are J-shaped with no clear fracturing of the particles, and are well correlated by an exponential–polynomial equation. </p>

Spherical agglomerates of benzoic acid crystals have been successfully prepared by drowning-out crystallization in three solvent partial miscible mixtures. Benzoic acid is dissolved in ethanol, bridging liquid is added and this mixture is fed to the agitated crystallizer containing water. Fine crystals are produced by crystallization of the substance, and the crystals are agglomerated by introduction of an immiscible liquid called the bridging liquid. The concentration of solute, agitation rate, feeding rate, amount of bridging liquid and temperature are found to have a significant influence on the physico-mechanical properties of the product. The product particle characterization includes the particle size distribution, morphology and mechanical strength. Many of the solvents such as chloroform, toluene, pentane, heptane, cyclo hexane, diethyl ether and ethyl acetate were used as bridging liquids. Among the selected solvents ethyl acetate and di ethyl ether could not form the spherical agglomerates. Characteristics of the particles are changing with the bridging liquid used. Range of the operation for spherical agglomeration is very narrow and was shown that only at certain conditions the spherical agglomerates are produced. Increased amount of bridging liquid, decrease in feeding rate and temperature causes the particle size to increase. Particle morphology depends on the bridging liquid used, amount of bridging liquid and the temperature. Particles look completely spherical from the experiments where toluene is used as bridging liquid. The mechanical strength of single agglomerates has been determined by compression in a materials testing machine, using a 10N load cell. For single particle compression an approximate estimation of the true stress is presented. Compression characteristics for single agglomerates are compared with data on particle bed compression. Low elastic recovery and high compressibility of the single particles and of bed of particles reveals that the spherical agglomerates prepared in this work have a plastic behavior which is expected to be favorable for direct tabletting. Some of the stress–strain curves are J-shaped with no clear fracturing of the particles, and are well correlated by an exponential–polynomial equation. / QC 20101119

Spherical agglomerates of benzoic acid crystals have been successfully prepared by drowning-out crystallization in three solvent partial miscible mixtures. Benzoic acid is dissolved in ethanol, bridging liquid is added and this mixture is fed to the agitated crystallizer containing water as the anti-solvent. Small crystals are produced by crystallization of the substance, and the crystals are agglomerated through the action of the bridging liquid. Different solvents: chloroform, toluene, heptane, pentane, cyclohexane, ethyl acetate and diethyl ether are chosen as bridging liquids, all being low soluble in water and showing good wettability for benzoic acid crystals. The influence of process conditions such as concentration of solute, agitation rate, feeding rate, amount of bridging liquid and temperature on the properties of benzoic acid spherical agglomerates, are investigated. Different sets of experiments were accomplished to track how the properties of the particles gradually change during the normal spherical crystallization experiment. Other sets of experiments were performed to examine the influence of agitation and process time for agglomeration. The product properties such as particle size distribution, morphology and mechanical strength have been evaluated. The mechanical strength of single agglomerates has been determined by compression in a materials testing machine, using a 10 N load cell. Compression characteristics for single agglomerates are compared with the data on bed compression. The present study shows that the bridging liquid has significant influence on the product properties, using diethyl ether and ethyl acetate no agglomerates are formed. Using any of the other five solvents (chloroform, toluene, heptane, pentane, and cyclohexane) spherical agglomerates are formed, as long as a sufficient amount of the bridging liquid is used. Using cyclohexane as bridging liquid at 5°C and toluene at 20°C the particles are larger compared to particles formed at other conditions. The highest particle fracture stress is obtained by using toluene as the bridging liquid at 5 and 20°C. Particle morphology depends on the bridging liquid used and the particles are completely spherical when toluene and pentane are used as bridging liquids. Different process parameters are found to have a significant influence on the physico-mechanical properties of the product. The range of operation for spherical agglomeration is relatively narrow and only at certain conditions spherical agglomerates are produced. With increasing amount of bridging liquid the particle size and strength increase and the morphology improves. Particle size decreases and the fracture force increases with increasing feeding rate, but the morphology remains unchanged. For all the solvents, the particle size and the fracture stress increase with decreasing temperature. For four of the solvents the morphology improves with decreasing temperature. For cyclohexane the result is the opposite, in that the particles are spherical at 20°C and irregular at 5°C. Spherical agglomerates of benzoic acid, both as single particles as well as in the form of a bed, have a high compressibility and low elastic recovery, properties that are favorable for direct tabletting. As the feed solution is supplied to the crystallizer the amount of benzoic acid that can crystallize actually does crystallize fairly rapidly. Hydrodynamics are responsible for bringing particles together for the agglomeration. Experiments reveal that during the gradual addition of the feed to the agitated aqueous solution, both particle size and particle number increases. It is clear from the experiments that not only further addition of feed solution leads to larger product particles but also continued agitation. Along the course of the process the properties of the particles change gradually but substantially. By continued agitation, the particle porosity decreases, density, strength gradually increases and also the spherical shape develops gradually. / QC 20110419

Proteins are important biological products with unique functions, annually produced at the hundreds of millions of dollars value on a worldwide basis. The application of crystallization for these materials primarily was led by structural biologists and crystallographers who are keen on obtaining large and well-ordered crystals for protein structure determination via X-ray diffraction. Usually for this, crystallization is done on a small scale by vapor diffusion using a supersaturated solution of the material. In the past decades, production crystallization has slowly received increasing attention for the large-scale recovery of proteins. Among the numerous products, an industrial enzyme (alpha-amylase) that is extensively involved in food processing and laundry products was chosen for examination due to the lack of relevant data in the literature and the potential industrial interest in crystallizing this material. The chosen alpha-amylase is a product of Genencor International (the Danisco division) and is derived from a genetically modified Bacillus licheniformis. In parallel to the underlying principles that govern the bulk crystallization of small molecules, the broad topics of investigation for this macromolecular material included determination of solubility, studies of nucleation thresholds, and investigation of crystal growth kinetics and special phenomena accompanying the crystallization process. All these studies were preceded by a series of characterization tests conducted for the material. On the whole, this study aimed to extend the existing fundamental knowledge of bulk crystallization for biological macromolecules. Specifically, it intended to enrich the solubility and crystallization kinetic data for the alpha-amylase. The experimental data of this study were all obtained at conditions in line with industrial practice, which included the use of moderate temperatures, mild pH conditions and simple inorganic salts ((NH4)2SO4, Na2SO4 and NaCl) in order for the findings to be transferred to the industry directly. In a 20 mM sodium phosphate buffer (with no added salts), alpha-amylase solubility increased with solvent temperature and had a minimum at pH between 6.4 and 7.1. A generalized equation (as a function of pH and temperature) was obtained to correlate the data. The three inorganic salts examined affected the alpha-amylase solubility in a different manner, both qualitatively and quantitatively. Evidently, the interaction effect of a salt varied with solution pH. This confirms the importance of studying solubility with the two or more condition parameters at the same time. With relevance to crystal growth, the metastable region of the material was relatively wide at (NH4)2SO4 and Na2SO4 concentrations corresponding to maximum solubility. For example, σSNT was 1.2  0.2 in solutions with 5 wt% ammonium sulfate at pH 7.0 and 25oC. A wide metastability range is useful for the practical operation of batch crystallizers as nucleation can be minimized. This range, however, diminished as the salt concentration increased beyond the maximum solubility points, imposing a limit on the range of salt concentration favorable for growth processes. In systems with no added salts at pH 7.0, the solution metastability was slightly higher at 10oC than at 40oC. This would suggest a future further examination of the salt system at a lower temperature, say of 10oC. To develop a batch crystallizer, the growth kinetic data of the material have to be known. Throughout the growth studies, the alpha-amylase crystals obtained were lozenge-shaped thin plates. Apparently, habit was not influenced by the crystallization conditions chosen. Similar to other proteins crystallized in bulk, the growth rate of alpha-amylase demonstrated a second-order dependence upon supersaturation. Importantly, the alpha-amylase demonstrated crystal growth rate dispersion (GRD) under all the conditions tested. To simplify the analysis of growth kinetic results, the seed crystals used were common history (CH) seeds whose growth rates are proportional to their sizes. The spread of growth rates (CV) was 0.54 for the unsieved CH seeds used. Due to GRD, growth rate coefficient data varied with crystal size. For instance, in solutions containing 5 wt% ammonium sulfate at pH 7.0 and 25oC, the growth rate coefficient for seed crystals initially at 20 m was 2.47 m/hr. This order of magnitude was equivalent to that of many other proteins. Although being small, industrial crystallization was feasible with these kinetics, as demonstrated by the sample design calculations included. To improve the design, it is recommended to further examine the solubility, metastability and growth kinetics of the above system at other temperatures to obtain a wider growth rate range. As the important phenomenon of growth rate dispersion has seldom been examined for protein and enzyme materials in the crystallization literature, this study is a significant contribution to this area.

Silicium wird während des Ätzvorgangs von Solar-Wafern mit HF-HNO3-Mischungen hauptsächlich zu Hexafluorosilicat (SiF62-) umgewandelt, welches sich negativ auf den Ätzabtrag, die Reaktivität der Ätzlösung und die Oberflächeneigenschaften der Wafer auswirkt. Möglichkeiten, das Silicium als SiF62- abzutrennen, sollten in dieser Arbeit untersucht werden. Voraussetzung für Abtrennungsuntersuchungen war eine quantitative Bestimmung des SiF62- in Ätzlösungen mittels Ramanspektrometrie. Als Abreicherungs-möglichkeiten des Siliciums in Form von Hexafluorosilicat wurden einerseits das Ausfrieren als Hydrat der Hexafluorokieselsäure (H2SiF6•nH2O) und andererseits die Fällung als K2SiF6 untersucht. Die experimentellen Ergebnisse wurden jeweils gestützt durch thermodynamische Modellierungen: die Tieftemperaturphasendiagramme wurden durch eine modifizierte BET-Modellierung bestätigt, die Löslichkeiten durch Nutzung des SIT-Ansatzes. Demnach erwies sich die Ausfällung als K2SiF6 als ökonomisch günstigste Variante.:Inhaltsverzeichnis 1 Einleitung und Problemstellung 2 Auswertung der Literatur 2.1 Chemie des Siliciums in HF/HNO3-Ätzlösungen 2.1.1 Allgemeine Betrachtungen zum Ätzvorgang 2.1.2 Rolle des H2SiF6 bzw. SiF62- beim Ätzen 2.2 Speziation des Siliciums in fluoridhaltigen Lösungen 2.2.1 Schwingungsspektroskopie 2.2.2 Kernresonanzspektroskopie 2.2.3 Gleichgewichtskonstanten 2.3 Phasendiagramme im System HF-H2SiF6-HNO3-H2O bei tiefen Temperaturen 2.3.1 Binäre Systeme 2.3.2 Ternäre und höhere Systeme 2.3.3 Thermodynamische Modellierung konzentrierter Elektrolytlösungen mittels modifiziertem BET-Modell 2.4 Charakteristik kristalliner Hexafluorosilicate 2.4.1 Allgemein 2.4.2 Eigenschaften des K2SiF6 2.4.3 Struktur des K2SiF6 2.4.4 Thermisches Verhalten von K2SiF6 2.5 Thermodynamische Modellierung von Löslichkeiten 2.5.1 Specific Ion Interaction Theory 2.5.2 Pitzer-Modell 2.5.3 Modellierung nach Pitzer- Simonson- Clegg 2.5.4 (e)PC-SAFT EOS 2.5.5 Zusammenfassender Vergleich der Modelle 2.5.6 Vorliegende Daten als Grundlage einer Modellierung 2.5.7 Wahl eines geeigneten Löslichkeitsmodells 3 Experimentelle Untersuchungen zur Ramanspektroskopie wässriger Fluorosilicatlösungen 3.1 Messbedingungen und Messküvetten 3.2 Spektren im System HF-H2SiF6-HNO3-H2O 3.3 Quantitative Bestimmung von SiF62- und HNO3 4 Phasendiagramme im System HF-H2SiF6-HNO3-H2O bei tiefen Temperaturen (<273 K) 4.1 Versuchsaufbau zur thermischen Analyse 4.2 Durchführung und Auswertung von Temperatur-Zeit-Kurven am Beispiel des binären Systems HF-H2O 4.3 Ergebnisse 4.3.1 Binäre Systeme 4.3.2 Ternäre Systeme 4.3.3 Quaternäres System 4.4 Modellierung der Phasendiagramme mit dem BET-Modell 5 Löslichkeit von K2SiF6 in Ätzlösungen 5.1 Methodik und Analysentechniken 5.2 Ergebnisse in Lösungen des Systems HF-H2SiF6-HNO3-H2O-K2SiF6 5.3 K2SiF6-Löslichkeit in KF- bzw. KNO3-haltigen wässrigen Lösungen 5.3.1 Löslichkeitskurven 5.3.2 Struktur und Eigenschaften des K2SiF6∙KNO3-Doppelsalzes 5.4 Quantitative Beschreibung der Löslichkeit von K2SiF6 in HF-H2SiF6-HNO3-H2O 6 Beurteilung der Trennverfahren 7 Zusammenfassung Literaturverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Symbole und Abkürzungen Anhang Eidesstattliche Versicherung Danksagung