Polymorphism of D-mannitol: Crystal structure and the crystal growth mechanism

The polymorphism of D-Mannitol(mannitol) is reviewed in this paper. It was found that the structure of the stable form is consistent in most literatures, but different authors have given different information about the two metastable forms. Therefore the commonly used nomenclature of mannitol was summarized based on the crystal unit cell parameters with the help of X-ray powder diffraction. Moreover, the crystal growth mechanism of mannitol polymorphs was summarized. Considering the lack of kinetic data for the metastable form especially, a reported method was attempted to apply to δ mannitol in an aqueous cooling crystallization process based on the induction time previously measured, and it was identified that the growth of the δ form follows the two-dimensional(2D) nucleationmediated mechanism. The results also indicate that the method based on induction time and supersaturation should have the potential to be expanded to the metastable polymorphs for the growth property study in a bulk system.     

Curse and Blessing of Non-Proteinogenic Parts in Computational Enzyme Engineering

Enzyme engineering aims to improve or install a new function in biocatalysts for applications ranging from chemical synthesis to biomedicine. For decades, computational techniques have been developed to predict the effect of protein changes and design new enzymes. However, these techniques may have been optimized to deal with proteins composed of the standard amino acid alphabet, while the function of many enzymes relies on non-proteogenic parts like cofactors, nucleic acids, and post-translational modifications. Enzyme systems containing such molecules might be handled or modeled improperly by computational tools, and thus be unsuitable, or require additional tweaking, parameterization, or preparation. In this review, we give an overview of common and recent tools and workflows available to computational enzyme engineers. We highlight the various pitfalls that come with including non-proteogenic compounds in computations and outline potential ways to address common issues. Finally, we showcase successful examples from the literature that computationally engineered such enzymes.     

Variation of particle size and its distribution during the synthesis of silicalite-1 nanocrystals

Recent studies imply that the external surface area of the nanozeolite product may, at least in some cases, be related to the average size of the particle population participating in aggregative nucleation, a population which itself is a product of aggregation of even smaller primary nanoparticles. This possibility puts more importance on our understanding of the variation of particle size and its distribution during the crystallization of zeolite nanoparticles. Variation of the particle size and PSD during nanoparticle silicalite-1 crystallization was followed with respect to time by a laser light scattering device with a scattering angle of 173°, for several starting synthesis compositions. Effects of varying TPAOH and water contents in the starting synthesis mixtures on the variation with time of the particle sizes and PSDs, especially across the two distinct aggregation events, were investigated. The products were also analyzed by XRD and AFM. Parallel to the decrease in the average particle size of the final product population with increasing alkalinity and organic template content, its PSD was observed to become narrower too. A reversal in the dependence on TPAOH content, of the average size of the population formed by aggregation, with respect to that of the population participating in aggregation, was observed across both aggregation events, implying that smaller particles aggregated to form larger particles, while larger particles aggregated to form smaller particles during these processes, and this was also seen from the AFM images, to be reflected to the surface features of the final product particles.     

Microcrystallization of lactose during droplet drying and its effect on the property of the dried particle

Spray dried products with controlled crystallinity is desired to realize an improved quality and functionality of the final products. This study used the glass-filament single droplet drying technique to study lactose crystallization behaviour during convective drying. Single lactose droplets with different proportions of α- and β-isomers were subjected to air drying temperatures of 70 °C and 110 °C. Lactose particles dried at 70 °C with higher initial proportions of α-isomer showed the lowest dissolution rate. XRD analysis on the freshly dried particles showed that higher crystallinity was achieved with a higher air drying temperature and a higher initial α-isomer proportion. This observation was confirmed with the SEM observation of lactose particles that were both freshly dried and with a post-drying crystallization process. Dried lactose particles could have a two-layer morphology where the surface shell and the interior part possess different crystallinity, due to the different crystallization kinetics during drying. The results suggest that during drying there is a critical crystallization stage where both droplet temperature and moisture content are sufficiently high, constituting large T − T_g driving force. For rapid crystallization to occur. The findings provide experimental support for the solid-phase crystallization theory.     

The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach

The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of α polymorphic active pharmaceutical ingredient, using Carbamazepine form III as a model drug, and taking into consideration Quality by Design (QbD) approach to pharmaceutical development. A 2^(4-1) factorial screening design was implemented to identify the spiral jet-milling process variables that significantly affect the particle size distribution of milled samples. Diameter of injector nozzles, diameter of ring nozzles and air pressure were selected for further analysis using a 2^(3-1) factorial experimental design. Particle size distribution of additional samples was determined, while physicochemical properties were examined by differential scanning calorimetry (DSC), hot-stage polarized microscopy (HSPM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and compared to those of un-milled drug. The gathered results shown that applied experimental design approach is capable to predict material behavior and could help in better understanding of material behavior during jet-milling process. Created design space (DS) provides assurance of product quality, expressed as the powder particle sizes lower than 5 μm, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.     

Manipulating the size,the morphology and the polymorphism of acetaminophen using supercritical antisolvent (SAS) precipitation

The supercritical antisolvent technology is used to crystallize paracetamol particles. Supercritical carbon dioxide (scCO₂) is used as antisolvent. Ethanol, acetone and mixtures of ethanol and acetone are used as solvents. The initial concentration of paracetamol in the solution was varied between 1 and 5 wt%, the composition of the ethanol/acetone solvent mixture between 50 and 90 wt% of ethanol and the operation pressure between 10 and 16 MPa at a temperature of 313 K. The most important finding is that the polymorph of paracetamol crystals can be adjusted between monoclinic and orthorhombic by varying the content of ethanol in the solution. The second important finding is that the occurrence of primary and secondary crystal structures can be explained solely by the overall supersaturation during the crystallization process. While X-ray diffraction was used to analyze the polymorph of the particles, their morphology was analyzed using scanning electron microscopy.     

The Relation of Collector Redox Potential to Flotation Efficiency: Monothiocarbonates

Abstract

The redox potentials of monothiocarbonates and xanthates have been determined and a correlation established with their collector properties for the flotation of galena. Flotation efficiency increases with the ease of oxidation of the collector. The role in flotation of the oxidation products, the disulfides, is discussed.     

Polymorphism and Mixing Phase Behavior in Ternary Mixture Systems of SOS–SSO–OSO: Formation of Molecular Compound Crystals

This paper reports the phase behavior of ternary mixtures of saturated and cis‐monounsaturated mixed‐acid triacylglycerols (TAG) of SOS (1,3‐distearoyl‐2‐oleoyl‐glycerol), SSO (1,2‐distearoyl‐3‐oleoyl‐rac‐glycerol), and OSO (1,3‐dioleoyl‐2‐stearoyl‐glycerol) examined with X‐ray diffractometry and a differential scanning calorimeter. The ternary mixtures were crystallized by cooling from melt (60 °C) to 5 °C, and the crystals were then stabilized by storing the mixture samples at 28 °C for 10 days. The following results were obtained. (1) Molecular compound (MC) crystals of stable β polymorph having a double‐chain‐length structure (β‐2) were formed in mixtures of SOS/SSO/OSO in which the concentration of SOS was 50% with varying concentrations of SSO/OSO. This is in contrast to the fact that the stable polymorphic forms of the component TAG are β‐3 for SOS and OSO and β′‐3 for SSO. (2) When the concentration of SOS deviated from 50%, immiscible mixtures of β‐2 MC made of SOS/SSO/OSO and the component TAG (β‐3 of SOS and OSO and β′‐3 of SSO) were formed. Therefore, ternary mixtures of SOS/(SSO + OSO) = 50/50 with different concentrations of SSO and OSO are miscible mixtures of β‐2 of SOS/SSO and SOS/OSO.     

Effect of comonomer type on the crystallization kinetics and crystalline structure of random isotactic propylene 1-alkene copolymers

Isothermal crystallization kinetics and properties related to the crystalline structure of four series of random propylene 1-alkene copolymers have been comparatively studied in this work. Comonomers studied include ethylene, 1-butene, 1-hexene and 1-octene in a concentration range up to 21 mol%. All copolymers were synthesized with the same metallocene catalyst to provide an equivalent random distribution and a similar content of stereo and regio defects within the series. This has ensured that differences in crystallization kinetics and in crystalline properties of copolymers with matched compositions reflect the affinity of the comonomer type for co-crystallization with the propene units, and the effect of content and type of co-unit in the development of the crystalline structure. In the nucleation-driven crystallization range, that is for T_cs > T_{c max}, the values of the rate follow the sequence PB > PE > PH = PO for comonomer contents <13 mol%, and PB > PE > PH > PO for >13 mol% comonomer. These trends in overall crystallization are guided by differences in undercooling due to a similar progression of the degree of participation of the comonomer in the crystalline lattice. The variation of the rates at T_cs < T_{c max} follows the melt segmental dynamics driven by differences in T_g, especially at the highest co-unit contents, resulting in a reverse rate sequence for PHs and POs >15 mol%, i.e., PB > PE ∼ PO > PH. In addition to crystallization kinetics, a comparative polymorphic analysis and unit cell expansion, crystalline morphology, and melting behavior have been instrumental in resolving the partitioning of the four types of co-units between crystalline and non-crystalline regions. 1-Butene units participate at the highest level followed by the ethylene units, as demonstrated by solid-state NMR. However, both units are defects that hinder crystallization, as given by the decreasing rates, decreased levels of crystallinity and lowered melting temperatures with increasing co-unit content. All crystalline properties of PHs and POs conform to a rejection model of the 1-octene units from the crystals in the whole compositional range, and rejection of the 1-hexene units for PH <13 mol%, a conclusion also supported by NMR. The ability of PH >13 mol% to pack comonomer-rich sequences into a stable trigonal lattice leads at T_cs > T_{c max} to an increased number of crystallizable sequences, and to faster crystallization rates than for matched PO copolymers.     

Measurement of particle size and shape by FBRM and in situ microscopy

In this work a model is defined allowing for a rapid calculation of chord length distributions as well as the prediction of in situ microscopy data. Both calculations are done using the same underlying algorithm. The model assumes convex polyhedral particles that are defined by their vertices only, connected by straight lines, but imposes no further restrictions on particle geometry. Due to its speed, the model can easily be used for the prediction of experimental data from in situ monitoring tools based on whole particle populations, also with non-constant shape. The model has been verified using in situ microscopy to characterize a population of disc shaped particles.The applications of the model are focused on crystallization processes, but are not limited to these. Several relations between data measured by in situ instruments and the underlying multidimensional particle size distribution have been derived. The model is used extensively in a method that is presented allowing for the calculation of bidimensional growth rates from Focused Beam Reflectance Measurement or in situ microscopy measurements.     

Monitoring the particle size and shape in the crystallization of paracetamol from water

In this work, a technique capable of restoring bidimensional particle size distributions from images of the particles in suspension is applied to the seeded cooling crystallization of paracetamol from water. The effects of cooling rate and stirring rate on the final particle size and shape are studied and the average growth rates along different directions of particles are found to be strongly dependend on supersaturation. This observation is in line with previous studies, though in this work it has been established for the first time using populations of particles. The technique was capable of quantifying changes in particle size and shape, indicating particle sizes and shapes that correlated well with observations from electron microscopy images.     

The atactic polystyrene molecular weight effect on the thermal properties and crystal structure of syndiotactic polystyrene/atactic polystyrene blends

This work examined how the molecular weight of atactic polystyrene (aPS) affects the thermal properties and crystal structure of syndiotactic polystyrene (sPS)/aPS blends using differential scanning calorimetry, polarized light microscopy and wide angle X-ray diffraction (WAXD) technique. For comparative purposes, the structure and properties of the parent sPS was also investigated. The experimental results indicated that these blends showed single glass transition temperatures (T_gs), implying the miscibility of these blends in the amorphous state regardless of the aPS molecular weight. The non-isothermal and isothermal melt crystallization of sPS were hindered with the incorporation of aPSs. Moreover, aPS with a lower molecular weight caused a further decrease in the crystallization rate of sPS. Complex melting behavior was observed for parent sPS and its blends as well. The melting temperatures of these blends were lower than those of the parent sPS, and they decreased as the molecular weight of aPS decreased. Compared with the results of the WAXD study, the observed complex melting behavior resulted from the mixed polymorphs (i.e. the α and β forms) along with the melting-recrystallization-remelting of the β form crystals during the heating scans. The degree of melting-recrystallization-remelting phenomenon for each specimen was dependent primarily on how fast the sPS crystals were formed instead of the incorporation of aPSs. Furthermore, the existence of aPS in the blends, especially the lower molecular weight aPS, apparently reduced the possibility of forming the less stable α form in the sPS crystals.     

The Role of Lipid Composition in the Sensory and Physical Properties of Lipsticks

The perception of lipstick texture upon application is a key driver of consumer satisfaction. However, formulators may only rely on the absence of knowledge about the relationship between ingredients and product sensory properties. Lipsticks are made of a complex anhydrous mixture that contains about 80% lipids (oils, waxes, and butters). The goal of this work was thus to investigate the combined effect of multiple lipid ingredients on the sensory and physical properties of a cosmetic product such as lipstick. To this end, we first analyzed a typical lipstick formula and its related categories of ingredients. This allowed us to create a simplified, yet realistic lipstick system. Based on this, we formulated 36 lipsticks varying in oil and butter composition according to three mixture designs. All products were evaluated by a panel of sensory experts—with a focus on the slipperiness and melting perception—and analyzed using texture measurements. The physical and sensory results both show that the oils had the strongest impact on the lipstick properties while the impact of the butter was negligible. Moreover, the perceived slipperiness of lipsticks was closely related to the viscosity of the oil mixture present in the formula (R² = 0.87). Further analyses of lipstick physicochemical properties by differential scanning calorimetry suggest that the nature and amount of oil influence the crystallization of butter and wax, which could explain the dominant impact of the oils on the sensory and mechanical properties of lipsticks.     

Supercritical antisolvent micronization of PVP and ibuprofen sodium towards tailored solid dispersions

The supercritical antisolvent technology is used to precipitate polyvinylpyrrolidone (PVP) particles and crystallise ibuprofen sodium (IS) crystals separately and in the form of solid dispersion together. Supercritical carbon dioxide (scCO₂) is used as antisolvent. For PVP particle generation, ethanol, acetone and mixtures of ethanol and acetone are used as solvents. The initial concentration of PVP in the solution was varied between 0.5 wt% and 1.5 wt%, the operation pressure between 10 MPa and 30 MPa and the composition of ethanol/acetone solvent mixtures between 100 wt% and 0 wt% of ethanol at a constant temperature of 313 K. Furthermore, the mean molecular weight of the polymer was varied between 40 kg mol⁻¹, 360 kg mol⁻¹ and 1300 kg mol⁻¹. An increase of the content of the poor solvent acetone in the initial solvent mixture as well as the usage of PVP with a higher molecular weight, leads to a significant decrease in mean particle size. At all the investigated parameters always fully amorphous PVP powder precipitates. For IS, only ethanol was used as the solvent, the initial IS concentration in the solution was varied between 1 wt% and 3 wt% and the operation pressure between 10 MPa and 16 MPa. A variation of these parameters leads to a manipulation of the size and the morphology of the crystallised IS crystals. Irrespective of the parameters used, always the same polymorphic form of ibuprofen sodium is produced. The solid dispersions were generated at different compositions of PVP to IS and with two different molecular weights of PVP at otherwise constant conditions. Fully amorphous solid dispersions consisting of IS and PVP together were generated at different ratios of PVP to IS.The mechanisms that control the final particle properties are discussed taking into account two different models for “ideal” and “non-ideal” solutes. Furthermore, the study of the “unconventional” SAS parameters, molecular weight and solvation power of the solvent shows that these parameters qualify to tailor polymer particle properties via SAS processing. Next to the investigation into the behaviour of both solutes separately, fully amorphous solid dispersions consisting of IS and PVP together were generated. While X-ray diffraction was used to analyze the crystalline structure of the particles, respectively, solid dispersions, their morphology was analysed using scanning electron microscopy (SEM).     

Computational Simulations for the Assessment of the Mechanical Properties of Glass with Controlled Porosity

Porous glass with closed controlled porosity is used as a model system in order to numerically assess the effect of pores on the macroscopic mechanical and fracture behavior of brittle solids. A computational code called OOF, which converts digitalized two-dimensional (2-D) images of materials microstructures into finite element meshes, is adopted, so that the effect of 2-D microstructural features (e.g. pore size and shape) on the global mechanical response of the material can be determined. Firstly, microstructures of porous glass bodies containing isolated pores were considered. These specimens were numerically investigated in terms of fracture initiation and propagation: the numerical model predicted that larger pores initiate fracture, in agreement with experimental results. Then, the effect of porosity on the elastic and fracture properties was thoroughly investigated by means of model two-dimensional microstructures consisting of selected area fractions of pores (equivalent to pore volume fractions in three dimensions) and with prescribed pore shape, orientation and dimensions. In particular, the effect of pore dimension and shape was studied, finding that the critical stress for crack initiation scales with pore dimension and aspect ratio, i.e. oblate and larger pores oriented perpendicularly to the stress direction cause a higher reduction of strength of the specimen. Finally, several 2-D microstructures characterized by different values of area fraction of pores of the same shape were investigated, in order to determine the variation of elastic properties and the fracture response of porous glasses with pore content. The study confirms the suitability of the 2-D OOF code to investigate the mechanical and fracture behavior of porous materials. Issues regarding the limitation of the model due to its 2-D character are also discussed where appropriate.     

Microstructural Characteristic and its Relation to Mechanical Properties of Clinocardium californiense Shell

The microstructures and mechanical properties of Clinocardium californiense shell were investigated in relation to the different parts of shell. It is found that the shell can be divided into three parts, that is, the dorsal side, body part, and marginal side based on the variation of microstructures along the longitudinal cross section. Specifically, all areas exhibit a cross‐lamellar structure on the dorsal side, and a hierarchical structure comprising three layers including inner (with a cross‐lamellar structure), middle (with a complex cross‐lamellar structure), and outer (with a prismatic structure) layers was observed on the body part, whereas on the marginal side, the orientation of aragonite sheets shows an obvious deflection. The structural architecture, the dimensions of different‐order lamellae in the same kind of structure and the orientation between the indenting direction and aragonite sheet all contribute to the unique mechanical properties of this shell. It is also found that a low value of the ratio of hardness‐to‐Young's modulus (H/E) corresponds to an improved indentation toughness. The middle layer with the densest and most complicated structure on the body part shows the lowest H/E ratio and the highest hardness and Young's modulus.     

A Study of the Combined Compaction and Drying of a Wet Crystal Mass

The combined compaction and drying of a wet crystal mass was studied using an industrial food processor and a custom built open turbo dryer setup. From extrapolation of an empirical relation for the porosity of a packed particle bed a qualitative idea of the influence of the constituent crystals an the minimum attainable porosity was obtained. It increases with increasing constituent crystal size and decreasing width of the crystal size distribution. From the experiments it was found that the compaction and size reduction of the wet crystal mass is mainly influenced by the characteristics of the premix. The compactibility and strength of the premix may be influenced by changing the saturation and the constituent crystal size and size distribution.     

Drying in the Context of the Overall Process

Abstract

Although drying has traditionally been considered as a unit operation, it is strongly affected by upstream operations such as crystallization and solid–liquid separation, and in turn can affect downstream processes such as gas cleaning and micronization. Process design needs to consider the complete flowsheet and the interactions between the different steps as early as possible. Key points are the particle formation method and the final product specification. The mean particle diameter and particle size distribution are vital parameters throughout the process, as smaller particles and fines make solids handling, dewatering, and washing more difficult. This in turn affects the inlet moisture content to the dryer, and hence the heat duty and performance. Intermediate size enlargement or reduction may be used to give a more easily dried particle or agglomerate. There are important links to the new subject of product engineering, for example in the choice of processing route to achieve a given product quality and specification. The interactions between the different process steps can affect process design, equipment selection and troubleshooting, and this is illustrated by industrial case studies. A holistic approach is proposed to allow the whole solids processing flowsheet to be optimized as an entity, rather than optimising each unit operation in isolation and then finding a conflict between them.     

The Adhesion Properties of Mortars in Relation with Microstructure

The interaction between masonry units and mortar is a crucial factor for the quality of a wall. The most important factor is the adhesion between bricks and mortar in order to construct a masonry wall with adequate strength, good impermeability, and durability. In this work mortars were produced with various cement/lime/aggregates ratio. The adhesion properties of the mortars with clay bricks were tested with a simplified tensile/tear testing measurement. In order to investigate the adhesion properties in relation with microstructure the mortars were characterized with X-ray diffraction and were further investigated with scanning electron microscopy and stereoscopy. It was found that adhesion is favored by the formation of a Si–Al matrix with a low Ca content in the brick/mortar interface and the formation of fine Ca–Al–Si phases which can penetrate into the brick.     

Crystallization Kinetics of Coconut Oil in the Presence of Sorbitan Esters with Different Fatty Acid Moieties

Sorbitan esters (SEs) are shown to strongly influence the solidification kinetics and fat crystal morphology, but not polymorphic behaviour, of coconut oil (CNO). Solid‐state SEs (sorbitan monopalmitate, monostearate, and tristearate) affect both the high‐ and low‐melting fractions of CNO by decreasing induction time and by increasing crystallization rate as well as the number concentration of crystals. Liquid‐state SEs (sorbitan monoleate and trioleate) and canola oil do not specifically influence the high‐ or low‐melting fraction of CNO but do slow crystallization and lengthen induction time. The influence of sorbitan monolaurate, the only SE with an acyl group similar to that of CNO, is shown to depend on the crystallization temperature. At temperatures below its melting point, it only affects CNO's high‐melting fraction; at temperatures above its melting point, crystallization of both fractions is extensively decelerated. The lack of influence in polymorphic behaviour by any SE confirms no alteration of subcell arrangement, suggesting a lack of complementarity with the crystallizing fat. Overall, these SEs significantly impact the crystallization kinetics of CNO; however, this largely depends on type and concentration.